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Page 385   E-mail  Facebook  Digg  Stumble  Twitter More The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. Index A Abscopal effect. See Bystander effects Absolute risk. See also Excess absolute risk defined, 132, 373 Absorbed dose atomic bomb survivors, 20, 27, 142 and biological effect, 20 defined, xi, 373 neutron weighting factor, 296-297 photon energy fluence and, 22 Achondroplasia, 92, 98, 125 Activity defined, 373 units of, 373 Acute myocardial infarction, 95 ada gene, 36, 37 Adaptive response animal studies, 51, 52, 53, 55, 78-79, 251 bacteria, 50 bystander effect and, 55 and cancer risk assessment, 250-251 cell cycle alterations, 51, 53 for cell lethality, 51, 52, 55, 78 in Chernobyl children, 51 to chromosomal aberrations, 51, 53, 55 cumulative effect of multiple low doses, 53 DDREF and, 78-79 to DNA damage and repair, 39, 50, 51, 52, 53, 251 dose fractionation and, 78 dose-response relationships, 45, 50-53, 62, 89 genotype and, 53 and hormesis, 333 in humans, 50 to iodine-131, 51 in lymphocytes, 51, 53 malignant transformation as, 51-52, 62, 78-79 in mammalian cells in vitro, 51, 52, 62 mechanisms, 11, 29, 39, 51-53 to medical uses of radiation, 51 in mice, 51, 52, 53, 55, 78 microarray expression studies, 39, 53 modeling, 250-251 mutagenesis as, 51 to occupational exposures, 51, 53 to oxidative stress, 50 priming dose and, 51-53, 55, 78, 251 radiation resistance as, 37, 51 research needs, 53 signal transduction pathways, 51, 53 in tumorigenesis, 12, 51-52, 78-79, 250-251 variation in, 51 Additive effects, 148, 150, 297, 373 Adenine phosphoribosyltransferase, 46 Adenocarcinomas, 50, 74, 76 Adenomas, 69, 151, 168 Adrenal cortical carcinoma, 86, 161 Adriamycin, 130 Adult Health Study, 142, 150, 151, 153 Aflatoxins, 242 Air and space travel, 3, 19 occupational exposures, 204 Alcohol consumption, 242 All-Union Distributed Registry, 202 Alpha particles and bone cancer, 87, 269 bystander effect, 53-54, 55 cell killing/lethality, 54 chromosome aberrations, 53 genetic susceptibility, 53, 87 and genomic instability, 70, 71 internal contamination, 199-200 LET value, 21 and leukemia, 71 and liver cancer, 68 and lung cancer, 242 mutagenesis, 53, 54, 68 RBE, 71 and tumorigenesis, 70 Amelogenesis imperfecta, 98 American Registry of Radiologic Technologists, 205 Animal studies. See also specific animals adaptive response, 78-79, 251 bone cancer, 74 breast/mammary cancer, 74, 82, 83, 88 DDREF from, 77-79, 254-258 DNA damage and repair mechanisms, 34, 36, 42, 52, 69, 71 dose-response relationships, 73-75, 89, 245 extrapolation to humans, 73, 96-98, 109-111, 114, 115 genetic effects of radiation, 12, 68-70, 73, 82-83, 92, 96-97 genetic susceptibility to cancer, 68-70, 71, 73, 82-83, 87-88, 89 of growth and developmental effects, 115 of hormesis, 334 leukemia, 68-70, 71, 72, 73-74, 87 life-shortening effects of radiation, 246 limitations of, 245 lung cancer, 28, 50, 74, 76, 87 lymphoma, 68, 73, 74, 76, 78 mutation rates, 68-70, 96-98 neutron RBE, 28-29, 68, 126 predictive value, 73, 75, 241 radiosensitivity, 34, 69, 71, 82-83 skin cancer, 74, 75, 76, 87 tumorigenesis, radiation-induced, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240, 241, 246 X-ray exposure, 68, 69, 100-101 Aniridia, 98 Ankylosing spondylitis cohorts bone cancer, 164 breast cancer, 164-165, 176, 177 cancer mortality, 164, 165 cohort description, 164 colon cancer, 164 dosimetry, 164, 165 esophageal cancer, 164 kidney cancer, 164 leukemia, 164, 165, 183, 289 lung cancer, 164, 174 malignant lymphoma, 164 modeling cancer risk in, 287 multiple myeloma, 164 pancreatic cancer, 164 prostate cancer, 164, 288 radiotherapy-related cancer risks, 164-165, 174, 176, 177, 185, 287, 288, 289 stomach cancer, 164, 185, 287, 288, 289 urinary tract cancer, 164, 288 Page 385 Front Matter (R1-R16) Public Summary & Executive Summary (1-18) 1 Background Information (19-42) 2 Molecular and Cellular Responses to Ionizing Radiation (43-64) 3 Radiation-Induced Cancer: Mechanisms, Quantitative Experimental Studies and the Role of Genetic Factors (65-90) 4 Heritable Genetic Effects of Radiation in Human Populations (91-131) 5 Background for Epidemiologic Methods (132-140) 6 Atomic Bomb Survivor Studies (141-154) 7 Medical Radiation Studies (155-188) 8 Occupational Radiation Studies (189-206) 9 Environmental Radiation Studies (207-238) 10 Integration of Biology and Epidemiology (239-258) 11 Risk Assessment Models and Methods (259-266) 12 Estimating Cancer Risk (267-312) 13 Summary and Research Needs (313-324) Appendix A: Basic Biological and Genetic Concepts (325-328) Appendix B: Commetary on "Radiation from Medical Procedures in the Pathogenesis of Cancer and Ischemic Heart Disease: Dose-Response Studies with Physicians per 100,000 Populations" (329-329) Appendix C: Issues Raised by the Institute for Energy and Environment Research (IEER) (330-331) Appendix D: Hormesis (332-335) Appendix E: Fifteen-Country Workers Study (336-336) References (337-372) Glossary (373-378) Committee Biographies (379-384) Index (385-406)

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Index A Abscopal effect. See Bystander effects Absolute risk. See also Excess absolute risk defined, 132, 373 Absorbed dose atomic bomb survivors, 20, 27, 142 and biological effect, 20 defined, xi, 373 neutron weighting factor, 296-297 photon energy fluence and, 22 Achondroplasia, 92, 98, 125 Activity defined, 373 units of, 373 Acute myocardial infarction, 95 ada gene, 36, 37 Adaptive response animal studies, 51, 52, 53, 55, 78-79, 251 bacteria, 50 bystander effect and, 55 and cancer risk assessment, 250-251 cell cycle alterations, 51, 53 for cell lethality, 51, 52, 55, 78 in Chernobyl children, 51 to chromosomal aberrations, 51, 53, 55 cumulative effect of multiple low doses, 53 DDREF and, 78-79 to DNA damage and repair, 39, 50, 51, 52, 53, 251 dose fractionation and, 78 dose-response relationships, 45, 50-53, 62, 89 genotype and, 53 and hormesis, 333 in humans, 50 to iodine-131, 51 in lymphocytes, 51, 53 malignant transformation as, 51-52, 62, 78-79 in mammalian cells in vitro, 51, 52, 62 mechanisms, 11, 29, 39, 51-53 to medical uses of radiation, 51 in mice, 51, 52, 53, 55, 78 microarray expression studies, 39, 53 modeling, 250-251 mutagenesis as, 51 to occupational exposures, 51, 53 to oxidative stress, 50 priming dose and, 51-53, 55, 78, 251 radiation resistance as, 37, 51 research needs, 53 signal transduction pathways, 51, 53 in tumorigenesis, 12, 51-52, 78-79, 250-251 variation in, 51 Additive effects, 148, 150, 297, 373 Adenine phosphoribosyltransferase, 46 Adenocarcinomas, 50, 74, 76 Adenomas, 69, 151, 168 Adrenal cortical carcinoma, 86, 161 Adriamycin, 130 Adult Health Study, 142, 150, 151, 153 Aflatoxins, 242 Air and space travel, 3, 19 occupational exposures, 204 Alcohol consumption, 242 All-Union Distributed Registry, 202 Alpha particles and bone cancer, 87, 269 bystander effect, 53-54, 55 cell killing/lethality, 54 chromosome aberrations, 53 genetic susceptibility, 53, 87 and genomic instability, 70, 71 internal contamination, 199-200 LET value, 21 and leukemia, 71 and liver cancer, 68 and lung cancer, 242 mutagenesis, 53, 54, 68 RBE, 71 and tumorigenesis, 70 Amelogenesis imperfecta, 98 American Registry of Radiologic Technologists, 205 Animal studies. See also specific animals adaptive response, 78-79, 251 bone cancer, 74 breast/mammary cancer, 74, 82, 83, 88 DDREF from, 77-79, 254-258 DNA damage and repair mechanisms, 34, 36, 42, 52, 69, 71 dose-response relationships, 73-75, 89, 245 extrapolation to humans, 73, 96-98, 109-111, 114, 115 genetic effects of radiation, 12, 68-70, 73, 82-83, 92, 96-97 genetic susceptibility to cancer, 68-70, 71, 73, 82-83, 87-88, 89 of growth and developmental effects, 115 of hormesis, 334 leukemia, 68-70, 71, 72, 73-74, 87 life-shortening effects of radiation, 246 limitations of, 245 lung cancer, 28, 50, 74, 76, 87 lymphoma, 68, 73, 74, 76, 78 mutation rates, 68-70, 96-98 neutron RBE, 28-29, 68, 126 predictive value, 73, 75, 241 radiosensitivity, 34, 69, 71, 82-83 skin cancer, 74, 75, 76, 87 tumorigenesis, radiation-induced, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240, 241, 246 X-ray exposure, 68, 69, 100-101 Aniridia, 98 Ankylosing spondylitis cohorts bone cancer, 164 breast cancer, 164-165, 176, 177 cancer mortality, 164, 165 cohort description, 164 colon cancer, 164 dosimetry, 164, 165 esophageal cancer, 164 kidney cancer, 164 leukemia, 164, 165, 183, 289 lung cancer, 164, 174 malignant lymphoma, 164 modeling cancer risk in, 287 multiple myeloma, 164 pancreatic cancer, 164 prostate cancer, 164, 288 radiotherapy-related cancer risks, 164-165, 174, 176, 177, 185, 287, 288, 289 stomach cancer, 164, 185, 287, 288, 289 urinary tract cancer, 164, 288

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Antibody genes, 34 Antitumorigenic defenses, 67 APC gene, 66, 80, 82, 83 Apert’s syndrome, 98, 103 Aplastic anemia, 153 Apoptosis, 48-49, 54, 55, 67, 80, 81, 88, 373 Apurinic-apyrimidinic endonuclease (APE1), 32, 33 Apurinic nucleases, 35, 42 Arthroses, 165 Asbestos, 200 Ashkenazi Jews, 85 Ataxia telangiectasia, 35, 36, 79, 80, 81, 82, 83, 86, 93 ATF3, 56 Atherosclerosis, 185, 186 ATM gene, 67, 80, 84, 86 ATM kinase, 35, 36, 37, 39, 50, 56 Atomic Bomb Casualty Commission, 91, 141 Atomic bomb survivors Adult Health Study, 142, 150, 151, 153 age and cancer risks, 72, 143, 144, 145, 147, 148, 149, 240, 297-298 autopsy data, 151, 152, 153 benign neoplasms, 150, 151-152 bladder cancer, 147, 148, 269, 303-306 bone cancer, 269 breast cancer, 12, 26, 85, 135, 147, 148-149, 170, 177, 180, 243, 269, 303-306 cancer risk assessment, 7-8, 138, 143-154, 239-240, 241-245, 262, 275-276, 285-286, 296-308 cardiovascular disease and stroke, 1, 8, 152, 153, 185 cataracts, 153 children of, 6, 8-9, 114, 118, 129, 130-131, 149, 151 chromosome nondisjunctions, 131 cohort description, 13, 141, 142-143 colon cancer, 147, 148, 149, 151, 269, 303-306 compatibility of data with other cohorts, 267-268 Committee’s analysis of data, 267-268, 296-308 confounding and bias in studies, 141, 146, 152-153, 268, 297 cytogenetic studies, 68 data used in this study, 13, 142, 144 DDREF, 246-250, 254-258 deaths from cancer, 142, 143, 144, 145, 147, 151 digestive system cancers, 149 dose-response relationships, 6, 13, 24, 45, 68, 72, 137, 140, 142, 143, 144, 145-146, 147, 149, 150, 151, 152, 153, 245 dosimetry, 6, 9, 10, 20, 24, 27, 72, 129, 134, 139, 141, 142-143, 144, 266 doubling dose, 7, 8, 118, 124, 130-131, 252 DREF, 146 esophageal cancer, 147, 148, 149, 215, 269 extrapolation to low dose rates, 146 follow-up, 8, 134, 239-240, 245 gall bladder cancer, 147, 148, 149, 269 genetic risk assessment, 8-9, 91, 92, 114, 115, 118, 131, 252 health end point data, 13, 76-77, 130, 131, 142 healthy survivor effect, 152 in utero exposures, 151, 172 incidence of cancer, 13, 130, 142, 144-145, 148-149, 151, 298-307 infant and childhood mortality, 8 kidney cancer, 149, 269 leukemia, 68, 72, 142, 143, 144, 153, 172, 240, 244, 245, 269, 307-308 life shortening, 153-154 Life Span Study, 9, 12-13, 26, 141-154, 239-240, 242, 245, 246-250, 267-268, 296-308 limitations of studies, 141, 240 liver cancer, 147, 150, 148, 149, 242, 269, 303-306 lung cancer, 68, 147, 148, 150, 215, 242, 269, 276, 303-306 lymphoma, 151, 153 medical exposure data combined with, 146-147 mental retardation, 1 mortality data, 130, 131, 141, 142, 143, 144, 145, 147, 151, 152-153, 298-307 multiple myeloma, 151 mutation rates, 6, 114, 129, 130-131 nervous system cancers, 148, 149, 151, 152 neutron RBE, 20, 27, 142, 143, 146 nonneoplastic disease, 13, 143, 152-153 nuclear industry workers compared, 201, 203 oropharyngeal cancers, 148, 149 ovarian cancer, 147, 148, 149, 269, 303-306 pancreatic cancer, 147, 148, 149 prostate cancer, 147, 148, 149, 303-306 rectal cancer, 147, 148, 149 respiratory system cancers, 149 salivary gland cancer, 149-150, 269 sex differences, 144, 145, 150, 151, 153 site-specific cancers, 147-151, 303-307 skin cancers, 148, 149, 150-151, 269, 295 smoking effects, 150, 276 solid cancers, 13, 45, 130, 142, 143, 144-147, 149, 245, 297-305 statistical analyses, 143-144 stomach cancer, 147, 148, 149, 150, 173-174, 215, 240, 242, 269, 303-306 suicides, 153 thyroid cancer, 148, 149, 181, 269, 295 transport of risks to other populations, 14, 240, 241-245, 267-268, 275-276 two-stage clonal expansion model applied to, 262 uncertainties in data, 130, 131, 141, 147, 172, 285-286 urinary tract cancer, 148, 149 uterine cancer, 147, 148, 149, 303-306 Atomic Energy Authority (UK), 190, 191, 192, 195, 196, 197, 198, 199, 232, 233 Atomic Energy of Canada Ltd., 191, 192, 195, 196, 197, 199 Atomic Weapons Establishment (UK), 190, 191, 192, 194, 195, 196, 197-198, 232, 233 ATR, 36, 37, 39 Attributable risk, defined, 373 Autoimmune diseases, 225 Autoimmune hypothyroidism, 151 Autopsy data atomic bomb survivors, 151, 152, 153 noncancer diseases, 151, 152, 153 B Background radiation. See Natural background radiation Bacteria adaptive response, 50 DNA repair, 36, 37 tumor promotion, 241-242 Basal cell carcinoma, 66, 68, 69, 80, 84, 150-151, 167. See also Skin cancer BAX, 56 Bcl2, 49 BEAR report doubling dose method for humans, 96, 123 Becquerel, Henri, 2 BEIR I report doubling dose method for humans, 96, 97, 118, 122, 123 genetic effects estimation, 94 principles of risk estimation, 138 BEIR III report cancer risk models, 138 doubling dose method for humans, 118, 122-124 genetic risk estimates, 94, 94-95 BEIR V report, 92, 373 advances in risk estimates since, 115-116, 187 baseline frequencies of genetic diseases, 94-95, 96, 115, 117-118 cancer risk assessment, 138, 174, 187, 246, 265, 275, 282, 283, 291-292, 299 dose-rate reduction factor, 100 n.1, 246 doubling dose calculation, 94-96, 100 n.1, 115, 118, 123, 124, 252 environmental exposure studies, 208, 209-214 extrapolation of animal data to humans, 115 genetic disease risk estimates, 12, 94-95, 96, 115-116, 117-118, 252 leukemia model, 246, 282, 283 multifactorial disease estimates, 95, 96, 115, 117 mutation component, 94, 106, 115 occupational exposure studies, 190 Benign diseases. See also Ankylosing spondylitis cohorts; Thyroid diseases; Tinea capitis cohorts; other specific diseases in adults, 162-166, 183 age at exposure and, 151 in atomic bomb survivors, 150, 151-152 breast disease, 26, 151, 163, 174, 177, 180, 185, 287 in children, 26, 68, 155, 156, 166-170, 174, 176, 177, 180, 181, 182, 183 dose-response relationship, 151 genetic susceptibility, 80 hormonal infertility, 164 neoplasms, 80, 150, 151-152 peptic ulcer, 163, 174, 175, 185

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 radiotherapy effects, 155, 162-167, 181, 289 salivary tumors, 150 skin hemangiomas, 26, 168-169, 174, 175, 176, 177, 180, 181, 183, 185 thymus gland enlargement, 26, 167-168, 176, 177, 180, 181, 182 tonsil enlargement, 169 uterine bleeding, 163-164, 183 Beryllium, 200 Best’s macular dystrophy, 125 Beta particles defined, 373 skin cancer in mice, 75 Bias. See also Confounding factors; Uncertainties assessment of, 139 DDREF estimate, 250 defined, 373 in epidemiological studies, 132, 133, 135-136, 139, 140, 152, 173, 187, 208 information, 135-136, 139, 208, 276 misclassification of disease, 139, 152-153, 285 misclassification of exposure, 139, 207, 266, 285 random errors, 296 reduction strategies, 140 selection, 135, 139, 152, 203, 208 systematic errors, 266, 296 underascertainment or misclassification of cancer incidence, 285 Biological damage. See Chromosome aberrations; DNA damage; Genetic effects of radiation; Relative biological effectiveness critical sites, 27, 29, 47, 48, 54, 74 models, 147, 262-263 process during energy transfer, 20, 245 responses to, 11; see also DNA repair mechanisms and defects; Tumorigenesis, radiation induced Bladder cancer. See also Urinary tract cancer in atomic bomb survivors, 147, 148, 298, 303-306 radiotherapy-related, 157, 158, 162, 163, 164 risk models and estimates, 272, 278, 279, 280, 282, 284, 285, 294, 303-306 Bleomycin, 130 Blindness, 98 Bloom’s syndrome, 93 Bone cancer age factors and, 264 animal studies, 74 ankylosing spondylitis cohort, 164 in cervical cancer survivors, 157 childhood exposure and, 161, 167 dose-response relationship, 74, 75, 201, 264 genetic susceptibility, 80, 84 high-LET radiation and, 87, 269 human data, 84 in nuclear industry workers, 201 protracted exposure and, 75 radiotherapy-related risks, 157, 161, 162, 164, 167 risk models and estimates, 269, 282, 294 Bone marrow cells, 71, 72, 74, 80, 173 Bowen’s disease, 151 Brachytherapy, 162 Brain tumors, 80, 162, 164, 166, 167, 168, 169, 218 BRCA1 gene, 67, 80, 82, 83 BRCA2 gene, 80, 82, 83 Brca1 protein, 35, 36, 37, 38, 39 Brca2 protein, 35, 38 Breakage-fusion-bridge (B/F/B) cycles, 48, 71 Breast cancer, female additive risk, 148 age at exposure and, 26, 147, 149, 160, 167, 170, 176, 180 age-specific rates, 149 animal studies, 74, 82, 83, 88; see also Mammary cancer; specific animals in ankylosing spondylitis cohort, 164-165, 176, 177 in atomic bomb survivors, 12, 26, 85, 135, 147, 148-149, 170, 177, 180, 243, 269, 287 baseline lifetime risk estimates, 278 BEIR V model, 291-292 in benign breast disease cohorts, 26, 163, 177, 180, 243, 287 BRCA-type heritable, 67, 79, 80, 82, 83, 84, 85-86, 243 cardiovascular disease mortality, 186-187 in cervical cancer survivors, 26, 157-158, 176, 177 chemotherapy and, 159 Chernobyl accident and, 227 childhood exposures to radiation and, 26, 167, 168, 169, 172, 175, 176, 177, 180, 243, 287 chromosomal radiosensitivity and, 86 cobalt-60 irradiation, 186-187 coherence of BEIR VII model with other studies, 287 contralateral, in radiotherapy recipients, 160 diagnostic irradiation and, 170, 172, 176, 177, 287 dose fractionation and, 26, 170, 176-177 dose-response relationships, 74, 76, 86, 149, 157-158, 159, 160, 163, 168, 170, 172, 176, 178-180 dosimetry, 159, 178-180 epidemiological studies, 24-26, 157, 287 etiology, 243 excess absolute risk, 12, 25, 26, 149, 168, 243, 287, 305, 306 excess relative risk, 12, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244, 303, 304 in fluoroscopy cohorts, 26, 170, 176, 177, 180, 243, 287, 293 genetic susceptibility, 67, 79, 80, 82, 83, 84, 85-86, 87-88, 103, 243 in Hodgkin’s disease survivors, 158, 159, 176, 177 hormonal/reproductive factors, 76, 157-158, 159, 168, 169, 241, 243 hypersensitivity to radiation and, 56, 82 incidence, 148-149, 176, 177, 243, 278, 279, 280, 298, 303, 305 LET of radiation and, 24-26 leukemia in radiotherapy recipients, 159-160 lung cancer in radiotherapy recipients, 160, 174, 175 in mastitis treatment group, 26, 163, 177, 180, 287 MCF-7:W58 cell lines, 56 medical-exposure-related risks, 12, 26, 84, 86, 157, 160, 163, 176-180, 286, 287 modeling, 148, 273 mortality, 170, 172, 176, 177, 243, 278, 279, 280, 287, 298 multiplicative model, 148, 163, 243 pooled analyses of data, 12, 169, 180, 243, 268-269, 287 protracted exposure and, 176, 180, 243 in radiologic technologists, 205 radiotherapy-related risks, 26, 84, 86, 157, 159-160, 164-165, 167, 168, 169, 174, 175, 176, 177, 186-187, 205, 243, 287 risk assessment, 25-26, 85-86, 148-149, 176-180, 241, 243, 244, 272, 273, 275, 286, 287, 293, 303-306 risk estimates, 173, 176-180, 278, 279, 280, 282, 294 spontaneous rates, 26, 86 uncertainties in risk models, 25-26, 285 British Nuclear Fuels, 232, 233 Bromodeoxyuridine (BrdU), 48, 60-61 bub1, 39 Building materials, 3 Bystander effects, 9, 11, 29, 37, 39, 45, 53-55, 62, 70, 251 C c-fos transcription factor, 51, 53 c-jun N-terminal kinase (JNK), 55 c-jun transcription factor, 51, 53 Californium-252, 113 Canadian fluoroscopy study, 176 Canadian National Dose Registry, 190-191, 192, 194, 195, 196, 198, 199, 230, 262 Canadian National Mortality Data Base, 198 Canadian nuclear workers, 192-193, 195, 196, 197 Cancer. See also Carcinogenesis; Genetic susceptibility to cancer; Tumorigenesis, radiation induced; specific sites age (attained) and incidence of, 72, 143, 144, 145, 148, 149, 167-168, 180-181 age at exposure and, 7, 26, 74, 76, 86, 143, 147, 149, 150, 160, 167, 170, 176, 180, 181-182, 311 apoptosis and, 49 baseline rates, 268, 275, 373 in childhood following in utero exposure, 1, 6, 10, 112, 151, 172-173, 211, 226 data availability, 6 defined, 373 genes, 12, 67, 79, 80, 82, 83, 84, 85-86, 243; see also Oncogenes incidence, 73, 130, 142, 144-145, 148-149, 151, 194-198, 200, 201, 202, 203, 298-307 inherited predisposition, see Genetic susceptibility to cancer

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 metastatic, 150 misclassification of disease status, 139 mortality/life shortening, 2, 4-5, 28-29, 68, 76-77, 142, 144, 145, 151, 165, 170, 172, 174, 175, 176, 177, 181, 189, 191, 194-198, 200, 201, 202, 203, 204, 205, 209-212, 242, 243, 298-307 multifactorial nature of, 81, 88 multistep process, 75, 240, 241 registries, 13, 141, 142, 147-148, 150, 151, 152, 160, 166, 202, 203, 205, 226, 268 sex differences, 7, 73, 74, 144, 145, 150, 151, 161, 167, 176, 181, 244 Cancer cells. See also Cell cultures; In vitro assays Cancer patients. See Radiotherapy studies Cancer risk assessment. See also Atomic bomb survivors; Excess absolute risk; Excess relative risk; Linear no-threshold model; Linear-quadratic model; Model fitting; Models/modeling; Risk assessment; specific cancer sites absolute risk model, 242, 244, 245, 253-254, 268, 279-281, 283 adaptive response and, 250-251 additive model, 148, 150, 240, 241, 244-245, 254, 276 age dependencies, 143, 144-145, 147, 148, 149, 240, 262, 268, 269, 270, 271, 273, 274, 275, 278, 284, 285, 286, 296, 297-298, 311 alternative models, 271, 285-286, 298-302 analytical approach, 269, 296-302 atomic bomb survivors, 7-8, 12-13, 138, 143-154, 239-240, 241-245, 267-276, 285-286, 296-308 baseline incidence and mortality data, 268, 275, 278, 373 BEIR III estimates, 138 BEIR V estimates, 138, 174, 187, 265, 268, 275, 277, 282-283, 291-292, 299 biologically based models, 241, 245, 262-263 for bone cancer, 269 breast cancer (female), 25-26, 85-86, 148-149, 163, 176-180, 241, 243, 244, 268, 272, 273, 275, 282, 286, 287 bystander effects and, 251 calculation of lifetime risk, 264-265, 266, 277-278, 284-286, 310-312 for children, 10, 26, 161-162, 166-170, 181, 209 cohort effects in, 297, 302 comparability of study designs and, 241 comparison of BEIR VII estimates with other sources, 282-284, 291-296 confidence intervals, 14, 278, 279, 284, 286, 296, 299, 309 data used for BEIR VIII model, 267-268, 277, 283-284, 296-308 DDREF adjustment, 246-250, 254-258, 274, 275-276, 279, 280, 282, 283, 284, 285, 286 dose-response functions, 245-246, 262, 269, 274, 280, 298 dosimetry and, 241, 266, 268, 269, 285, 286, 296 DREF, 146 endpoints, 268-269 EPA estimates, 274, 275, 282-283, 293 estimates of lifetime risk, 145, 278-286 etiology at different histologic sites and, 241-245 examples of estimates, 310-312 extrapolation from high to low doses, 50, 146 genetic susceptibility and, 85-87, 88, 241, 251 genomic instability and, 251 human data for; see Epidemiological studies; Human cell lines/systems; Human studies ICRP estimates, 274, 282-283, 292-293 incidence data, 146, 268, 270, 271, 272, 273, 278, 279, 280, 281, 283, 284, 298-302, 311, 312 internal exposure and, 276 latent period, 302 for leukemia, 143, 144, 173, 183-185, 244, 245, 246, 268, 273-274, 275, 277, 278, 280-282, 289-290, 307-308, 309 lifetime attributable risk, 277-286, 309-312 liver cancer, 242, 272, 278, 279, 280, 282 lung cancer, 147, 148, 173, 174-176, 242, 244-245, 272, 275, 278, 279, 280, 282, 286 measures of risk, 268-269, 277 medical uses of radiation, 12, 26, 173-187, 240, 241, 276, 286-290 method of calculating lifetime risk, 277-278 model selection for this study, 6-8, 138, 269-274 modifying factors and, 240, 268-269 mortality data, 144-145, 268, 273, 275, 278, 280, 281, 282, 283, 298-302, 311, 312 multiplicative model, 148, 163, 240, 241, 242, 243, 254, 292 NCRP review of models, 274, 293 neutron RBE and, 28-29 NIH model, 268, 269, 273, 277-278, 293, 294-296, 299 nuclear industry workers, 138, 262, 268, 275, 290 parameter estimates, 268, 278, 279, 280, 284, 285, 308-309 parametric model, 143, 299 pooled analyses of data, 169, 180, 181, 243, 268-269, 273, 286 population modeling, 85, 88, 286 postirradiation cancer mechanisms and, 241 preferred (BEIR VII) model, 244, 269-278, 296-312 probability of causation in, 265, 294 RBE and, 28-29, 146, 276, 286 REID measure, 277 relative risk model, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244, 253, 279-281, 283, 307 RERF model, 269, 270, 271, 285, 286, 296, 298, 297, 301, 302, 307 results of calculations, 278-284 Rochester thymus cohort, 26, 180, 181, 273, 292 sex-specific, 267, 271, 274, 275, 278-281, 282-283, 284, 298, 301, 311, 312 site-specific, 88, 241-242, 268-269, 272-273, 275, 278, 282, 283, 284, 285, 292, 303-307, 311, 312 skin cancer, 245, 270-271, 282, 294, 295 solid cancers (all), 144-145, 268-273, 278, 279-280, 281, 282, 284, 287-289, 296, 297-302, 312 stratified-background relative risk model, 299 temporal projections, 239-240, 275 threshold models, 12, 74-75, 105-108, 120-121, 124 thyroid cancer, 181, 244, 268, 270-271, 272, 273, 275, 282, 286, 287 time since exposure, 271, 274, 275, 289, 296 tonsil irradiation cohort, 273 total cancer, 268, 282 transport between different populations, 85, 88, 240-245, 253-254, 265, 275-276, 277, 278-281, 284, 285, 286, 292 uncertainties in, 25-26, 147, 174, 241, 244, 251, 268, 272-273, 275, 276, 278, 279, 280, 284-286, 297, 308-310 UNSCEAR approach, 138, 240, 268, 272, 274, 275, 277-278, 282-283, 293-294, 297-298, 307 for U.S. population, 274-284, 286 Capenhurst nuclear workers, 191, 192, 195, 196 Carbon-14, 3 Carcinogenesis. See also Tumorigenesis, radiation induced age and, 262 Armitage-Doll model, 262 bystander effects and, 9, 29, 54 cell cycle effects, 49, 50, 86 frequency, 52 general mutagen model, 262 genetics of, see Genetic susceptibility to cancer latent damage, 65, 68, 72, 76, 78, 159, 167, 215 LET of radiation and, 24-26, 49 malignant transformation, 51-52, 62, 78-79, 262 mathematical theory of, 262 modifiers of, 200-201 protooncogenes, 66, 68, 80, 81-82 repair of injury, 76 smoking and, 242 two-stage clonal expansion model, 241, 253-254, 262 Carcinogens chemical, 244 defined, 373 and genetic polymorphism, 87 Cardiovascular disease, 8 in atomic bomb survivors, 1, 8, 152, 153, 185 in breast cancer survivors, 186-187 dose-response relationships, 152, 153 genetic factors, 95, 96 medical-exposure-related risks, 12, 159, 160, 163, 185-187 occupational exposures and, 199 Case control studies, 84, 133, 134-135, 136, 148, 172, 173, 190, 207, 208. See also Epidemiological studies; individual cohorts

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Chernobyl accident, 224, 225, 226 defined, 373 environmental radiation exposures, 211-212, 224-225, 229, 230, 233, 235 Casein kinase I and II, 39 Caspase cleavage, 49 Cataracts (early onset), 28, 98, 112, 115, 116, 153 Cell cultures. See also Human cell lines; In vitro assays; Lymphocytes systems; individual animal cell lines defined, 373 Cell cycle phase adaptive response in, 51, 53 and carcinogenesis, 49, 50, 86 and cell killing, 49, 50 and cellular response, 45, 49-50 checkpoint kinase gene, 86 and chromosome aberrations, 45, 46, 48, 49, 82 and DNA repair, 34, 37, 39, 48-49, 50, 245-246 dose-rate effects, 49-50, 55 dose-response relationship, 45, 50 and genomic instability, 49, 113 and mutagenesis, 49, 50, 81, 113 and neutron RBE, 50 and radiosensitivity, 45, 49-50, 55, 82, 83, 86, 113 regulator protein, 39 and translocations, 45 Cell cyclin proteins, 52 Cell killing/lethality. See also Apoptosis adaptive response, 51, 52, 55, 78 by alpha particles, 54 bystander effects, 9, 29, 54-55 cell cycle phase and, 49, 50 chemical modification of radiation effects, 31 delayed, 55 DNA damage response disorders and, 82 dose-response relationships, 55-57, 75, 78 gene mutation and, 47 hypersensitivity to radiation and, 55-57 by low-LET radiation, 55-57 and lymphoma, 74, 78 by neutrons, 28 oocyte sensitivity, 75, 98-99, 119 in radiotherapy patients, 155 signal, 56 target for, 27, 29, 74 and tumorigenesis, 12, 74, 75, 76, 82 Cell senescence, 72 Cellular response. See also Adaptive response; Cell killing/lethality; Chromosome aberrations; Genomic instability, radiation induced; Germ cells; Somatic cells bystander effects, 9, 29, 37, 39, 47, 53-55 cell cycle effects, 45, 49-50 hypersensitivity to radiation, 11, 32, 45, 47, 51, 55-57, 82 membrane damage, 29 multilocus mutations, 46 Central nervous system cancers, 151, 161, 166-167, 168-169 Cerebrovascular injury, 185 Cervical cancer survivors bone cancer, 157 breast cancer risk, 26, 157-158, 176, 177 dosimetry for radiotherapy, 26, 157 leukemia in, 157, 158, 183, 289 lung cancer, 157 lymphoma, 157 rectal carcinoma, 157 risk estimates, 287 secondary cancers in radiotherapy cohort, 26, 135, 157-158, 174, 176, 177, 185 stomach cancer, 158, 185, 288 thyroid cancer, 181 urinary tract cancer, 157, 158 uterine cancer, 157 Cervical polyps, 153 Cervical tubercular adenitis, 169 Cesium-137, 114, 128, 202, 212, 213, 214, 215-226, 276 Chalk River plant, 191 Chapelcross nuclear workers, 191 Chemical aspects of radiation background radiation, 30-31 DNA damage mechanisms, 29-30 electron ionization of water, 20, 21, 29-30 in locally multiply damaged sites, 31-32 oxidation reactions, 30, 31-32, 40-42, 48, 50, 54 spontaneous DNA damage, 29-30 Chemotherapy, additive effects of, 159, 244 Chernobyl accident adaptive response in children, 51 brain cancer, 218 breast cancer, 227 case control studies, 224, 225, 226 childhood cancers, 51, 68, 72, 114, 128, 215-226, 227, 235, 246 chromosome aberrations, 57 cleanup (liquidation) workers, 57, 58, 60, 114, 129, 202-204, 226, 227 congenital abnormalities, 218 DNA damage repair indicators, 222, 228 dose-response relationships, 224, 225, 226-227 dosimetry, 114, 128, 129, 202, 203, 216-223, 224 Down’s syndrome, 216 ecologic studies, 215, 216-223, 226 environmental exposures, 215-228, 234-235, 236 follow-up, 202-203 gastrointestinal cancers, 218 goiter, 218 human minisatellite loci mutations, 128-129 internal exposures, 276 kidney cancer, 227, 228 leukemia, 203-204, 216-222, 225-227 lymphoma, 217, 227 mutation rates, 114, 128, 129-130 population exposures, 114, 202, 215-228 registries, 202, 203 renal cell carcinoma, 222 respiratory tract cancers, 218 risk estimates, 203-204 solid tumors (nonthyroid), 227-228 thyroid cancer, 68, 72, 203-204, 215-226, 234-235, 246, 276 uncertainty in data, 128, 129, 202-203 urinary bladder cancer, 223, 227-228 Chernobyl Registry, 202 Children/childhood. See also Postradiation generation progeny of atomic bomb survivors, 6, 8-9, 114, 118, 129, 130-131, 149, 151 benign diseases, 26, 68, 155, 156, 166-170, 174, 176, 177, 180, 181, 182, 183 bone cancer, 161, 167 brain and central nervous system tumors, 161, 166-167, 168-169 breast cancer in women exposed during, 26, 167, 168, 169, 172, 175, 176, 177, 180, 243 cancer risk estimates, 10, 26, 161-162, 166-170, 181, 209 Chernobyl, 51, 68, 72, 114, 128, 215-226, 227, 235, 246 CT scans, 172-173 cytogenetic study, 68 descriptive studies, 208 diagnostic exposures, 155, 156, 172-173, 211 dose-response relationships, 10, 161, 162, 168, 169 doubling doses in, 130-131 endocrine gland tumors, 168 environmental exposures, 208, 209-210, 211, 212, 213, 215-226, 229, 233, 234, 235-238 genetic effects of radiation, 8-9, 68, 114, 118, 161 in utero radiation exposure, 1, 6, 10, 112, 151, 172-173, 211, 226 infants, 167-168, 175, 211, 218, 226, 287 iodine-131 exposure, 68, 169, 173, 215 leukemia, 84, 161, 168, 172, 209, 210, 211, 212, 214, 216-222, 226-227, 233, 244 lung cancer, 168, 175 lymphoma, 209, 210 melanoma, 161 mental retardation, 1 mutation frequencies, 114, 128, 130-131 pancreatic cancer, 168 parental preconception exposures, 8-9, 114, 130-131, 175, 214, 228-233 radiotherapy-related risks, 9, 84, 161-162, 166-170 retinoblastoma, 161 risk assessment, 6, 8-9 salivary gland tumors, 167 scoliosis, 172, 176, 177, 187 skin cancer, 161, 167 skin hemangioma cohort, 26, 168-169, 172, 174, 175, 176, 177, 178, 180, 181, 183, 185, 287 soft tissue sarcoma, 161 stomach cancer, 168, 185 thymus radiography cohort, 26, 167-168, 176, 177, 180, 181, 182, 243, 287, 292 thyroid cancer, 68, 72, 149, 161, 162, 166, 167, 168, 169, 181, 182, 214, 215-226, 234, 244, 246, 287 thyroid diseases, 169 tinea capitis cohort, 68, 155, 156, 166-167, 181, 182, 183

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 tonsil enlargement, 169 X-ray exposures, 211 Cholangiocarcinomas, 150 Chromatid instability breaks and gaps, 47, 58 in hematopoietic cells, 70-71, 86 in mouse mammary epithelial cells, 71-73 Chromatin remodeling, 69 Chromium-51, 200 Chromosomal diseases, 93, 96, 117, 119 Chromosome aberrations adaptive response, 51, 53, 55 alpha particles and, 53 aneuploidy, 48, 49, 69, 70, 83, 130, 131 breaks, 51 and breast cancer, 86 bridge formations, 45, 47, 48, 71 bystander effect, 53, 54, 55 cell cycle stage and, 45, 46, 48, 49, 82 centric rings, 45, 57, 58 centrosome defects, 48, 49 Chernobyl accident and, 57 and colon cancer risk, 86 complex exchanges, 46, 48, 67, 68 delayed, 54 deletions, 29, 30, 35, 46, 68, 69, 93 detection methods, 45-46, 57 dicentric exchanges, 24, 25, 28, 45, 46, 57, 58, 71 diseases arising from, 82, 93, 96 DNA repair defects and, 45-46, 57, 65 dose fraction and, 57 dose-response relationship, 24, 25, 45-46, 57-59, 60-61, 73, 74, 256, 257 frequencies, 46, 47-48 and genomic instability, 46, 47-48, 49, 54, 58, 59, 60-61, 70, 251 gross loss events, 66 heritable fragile sites, 69 in human lymphocytes, 24, 25, 28, 45, 46, 51, 53, 57, 58, 59, 61, 86 inversions, 48 late effects, 24 LET dependence, 45 in mammalian cells, 45 in mammary epithelial cells, 61, 71 mechanisms of induction, 45-46, 74 microsatellite sequence instability, 68, 72 monocentric exchanges, 45; see also Translocations neutron RBE and, 28 nondisjunctions, 131 in plant cells, 45 proximity effects, 45 rate of formation, 46 RBE and, 24, 27-28, 276 saturation effects at high doses, 45 spontaneous, 53 telomere-associated instability, 71-73 trisomy, 93 and tumorigenesis, 24, 46, 48, 66, 68-69, 70, 72-73, 74, 82, 86 Chromosomes basic concepts, 327 human, 5, 11, 21, 58, 59, 61, 93 Cigarette smoking. See Smokers/smoking Cisplatin, 34-35, 40 Cleft lip/palate, 93, 98 Coal-fired power plant emissions, 3 Cobalt-60 breast cancer and, 186-187 chromosome aberrations, 57 and heart disease mortality in breast cancer survivors, 186-187 LET value for electrons, 19 n.1, 21, 22, 24, 276 occupational exposure, 200 RBE, 24, 276 Cockaynes syndrome, 80 Cohort studies, 133, 134. See also Atomic bomb survivors; Radiotherapy studies Colon cancer in atomic bomb survivors, 147, 148, 149, 151, 269, 303-306 baseline lifetime risk estimates, 278 chromosome aberrations and, 86 genetic susceptibility, 66, 67, 79, 80, 86-87 hereditary nonpolyposis, 79 incidence, 278, 279, 284, 298, 303, 305 mortality, 278, 280, 282, 298, 304, 306 in radiologists and radiologic technologists, 205 in radiotherapy recipients, 163, 164, 288 risk models and estimates, 272, 275, 278-280, 282, 284, 287, 288, 294, 303-306 Colorectal cancer, 80, 82, 161 Combined UK Industrial Workforce study, 200 Committee of the British Medical Research Council, 91 Compton scattering, 20, 22 Computed tomography (CT) scans, 4-5, 156 Computer monitors, 3 Confounding factors in atomic bomb survivor studies, 141, 146, 152-153, 268, 297 birth cohort effects, 297, 302 chemical exposures, 233 control of, 138 country differences in baseline cancer rates, 268 defined, 133 in ecologic studies, 207 healthy worker/survivor effect, 136, 152, 189, 194, 205 lifestyle-related, 57, 138, 198, 199, 240 occupational exposures, 136, 189, 194, 198, 199-200, 205 socioeconomic status, 198 species variation in susceptibility, 73 stress, 71 Congenital disorders Chernobyl accident and, 218 doubling dose, 131 environmental radiation exposures and, 211, 229, 230, 232, 233, 235 frequencies, 112 in mice, 115, 116, 131 multifactorial nature of, 93, 95, 96, 112, 117 mutation component, 105-106, 111, 116 PRCF, 111 risk estimates, 115, 116, 117, 120 Connexin, 43, 54 Consumer product radiation, U.S. population exposure to, 3, 5 Contiguous gene deletion syndromes, 112 Cooperative Thyrotoxicosis Therapy Follow-up Study, 165, 166 Coronary heart disease, 81, 93, 106, 111 Cosmic radiation, 3, 4, 30, 43, 204 Cri du chat syndrome, 93 Crouzon’s syndrome, 103 CS-A, CS-B genes, 80 Cumene hydroperoxide, 40 Curie, Marie and Pierre, 2 Cyclin B1, 53 Cyclin-dependent protein kinase catalytic subunit, 127 Cyclodeoxynucleosides, nucleotide-excision repair, 32, 34-35 Cyclophosphamide, 130 Cystic fibrosis, 8, 93 Cytochrome c, 49 Cytogenetic studies, 68 Cytokines, 54 D Dally, Clarence, 2 Danish Cancer Registry, 160, 205 Deaf mutism, 98 Death certificates, reliability of data from, 142, 150, 152-153, 208, 303 Defense Radiological Protection Service (British), 190 Delayed lethality, 47 Dementia, 153 Dental radiography, 156 Dentinogenesis imperfecta, 98 Denys Drash syndrome, 80 Development. See Growth and Development effects Diabetes mellitus, 8, 93, 111, 113 Diagnostic radiography. See also Medical uses of radiation adults, 170-172 angiography, 156 and breast cancer, 170, 172, 176, 177 cancer mortality risk, 4-5, 68, 170, 176 children, 155, 156, 172-173, 211 CT scans, 4-5, 155, 172 cumulative doses, 156 dosimetry, 155, 156, 170, 176 fluoroscopy for pulmonary tuberculosis follow-up, 155, 170-171, 174, 175, 176, 177, 187 in utero exposures, 172-173 interventional procedures, 156 iodine-131 exposures, 171, 173, 234 and leukemia, 170, 171, 172 limitations of studies, 187 and liver tumors, 68 and lung cancer, 170, 174, 176 and lymphoma, 171 mammography, 4, 20, 21, 22, 24 photon energies, 20 radioisotope studies, 156 scoliosis, 155, 172, 176, 177, 187

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 techniques, 156 Thorotrast exposure, 68, 150 and thyroid cancer, 171, 234 uncertainties in risk estimates, 286 X-rays, 3, 4, 5, 6, 21, 22, 156, 171, 286 Diamide, 40, 42 Digestive system cancer. See also Colon cancer; Esophageal cancer; Rectal cancer; Stomach cancer in atomic bomb survivors, 149 risk estimates compared, 282, 292, 294 secondary, in radiotherapy patients, 159 DIR1 gene, 52, 56 DNA amplification, 48 DNA-binding proteins, 34 DNA concepts, 327, 374 DNA damage adaptive response to, 39, 50, 51, 52, 53 base removal, destruction, or mutation, 29, 30, 31, 32, 46, 54 and cancer risk, 239 chain breakage, 30, 46 chemically induced, 34-35 Chernobyl accident and, 222, 228 and chromosome aberrations, 45 dose-response relationship, 31, 73, 246-247 double strand breaks, 29, 30, 31, 45-46, 48, 52, 65, 70, 73, 245 free radicals and, 19, 29-30, 239 internucleosomal digestion of DNA, 49 LET of radiation and, 26-27, 31, 62 lethal, 31, 35, 42 locally multiply damaged sites (clustered damage), 26-27, 31-32, 34, 46, 48 low vs high dose and, 9-10, 31, 45, 46 measurement, 31 mechanisms, 29-30, 26-27, 29-32, 62 mutagenic, 35, 40, 65, 112 natural background radiation and, 30-31 oxidative, 19, 30-32, 34, 40-42, 50 prevention, 29-30, 34 probability from energetic electrons, 26-27 protracted, low-dose exposure and, 31 proximity-promoted interaction of lesions, 45 and radiosensitivity, 32, 34, 37, 56 resonance phenomenon, 29-30 sensors, 31, 50, 56, 69, 86 signaling presence of, 36, 50, 65 single-strand breaks, 29, 30, 31 spontaneous vs. induced, 30, 31, 34 strand invasion, 38 time dependence, 46 track characteristics and, 10, 45 from X-rays, 30, 32, 33, 36 DNA-DNA covalent cross-links, 30 DNA ligases, 32, 33, 34, 35 DNA-membrane complex, 29 DNA-PK, 35, 36, 39, 42, 71 DNA-protein covalent cross-links, 30 DNA radical, 29 DNA repair mechanisms and defects animal studies, 34, 36, 42, 52, 69, 71 in bacteria, 36, 37 base-excision, 32-34, 51, 53, 80, 87 bystander effect, 54 cell cycle phases and, 34, 37, 39, 48-49, 50, 245-246 and cell lethality, 82 in chick cells, 36 and chromosomal aberrations, 45-46, 57, 65 cross-overs, 32, 80 of cyclodeoxynucleosides, 34-35 dose-rate effects, 49, 56 of double-strand breaks, 32, 34-35, 36-39, 42, 45-46, 47, 49, 51, 65, 73, 81, 87 fast reaction, 35-36 and gene amplification, 47 genes, 36, 37, 39, 40, 42, 71, 86, 87-88 and genetic susceptibility to cancer, 71, 79-81, 87 and genome instability, 48, 49, 72 and growth and development, 34 Holliday junction, 36, 38 homeologous recombination, 36, 245-246 homologous recombination, 32, 35, 36, 38, 49 hypersensitivity to radiation and, 56, 71, 239 inducible, 36-39 of locally multiply damaged sites, 27, 31, 34, 35, 36 loss-of-function mutations, 67 in mammalian cells, 35, 36-37 microhomology-mediated, 38 of mismatches, 34, 80 molecular mechanisms, 32-39 nonhomologous end joining, 29, 32, 35-36, 40, 42, 46, 47, 48, 68, 70, 71, 80, 87, 245 normal processes, 32 nucleotide-excision, 32, 34-35, 87 oxidative processes and, 31-32, 40-42, 48 radiation resistance and, 49 and radiosensitivity, 32, 34, 37, 40, 56, 69, 71, 80, 82, 83, 87, 239 of refractory, complex breaks, 35, 36 signal transduction pathways, 32, 34, 36-39, 48, 49, 54, 80 of single-strand breaks, 32, 34, 56, 80 slow reaction, 35, 36 in somatic cells, 36 spontaneous vs. induced damaged, 31, 34 track of radiation and, 10, 43-44 and tumorigenesis, 6, 11, 65, 68, 69, 70, 73, 82, 83, 227-228, 239, 246 xeroderma pigmentosum patients, 79, 80, 81 in yeast, 30, 36, 40-42 Dogs, life-span shortening, 76 Dose. See also Absorbed dose; Effective dose; Equivalent dose, defined; Low doses combining low- and high-LET radiations, 2, 3, 199 conversion factors, xi defined, 374 estimating, 137, 166, 203, 207, 266; see also Dosimetry of ionizing radiation extrapolation of high to low, 9, 29, 44, 50, 54, 62, 146, 296 of internally deposited radionuclides, 3, 4 linear-quadratic function, 143 organ, 4, 143 population, 207 priming, 51-53, 55, 78 skin erythema, 2 units, xi, 2 variability within populations, 207 weighting factor, xi, 142, 143, 204, 275-276, 378 Dose and dose-rate effectiveness factor (DDREF) for acute doses, 60 adaptive response and, 78-79 from animal studies, 77-79, 246, 254-258 applications, 44, 282 for atomic bomb survivors, 246-250, 254-258 bias and variance of sample estimate of, 250 calculation, 44-45, 254-258 cancer risk assessment, 246-250, 254-258, 274-278, 282, 309 from cellular and molecular studies, 246, 256 defined, 246, 248, 374 derivation by Bayesian analysis, 246-250, 254-258 and dose-response relationship, 44-45, 60, 246-250, 254-258 extrapolation of high to low dose rates, 44, 247 gamma rays, 61 genetic risk assessment, 92, 246 ICRP value, 246, 282, 293, 297 for mutagenesis, 246 rationale for, 247 for tumorigenesis, 77-79, 246-250 uncertainties in, 279, 284, 285, 286, 295, 296, 310 UNSCEAR value, 131, 246, 249 Dose effectiveness factor (DEF), 44, 246 Dose fractionation. See also Diagnostic radiography adaptive response, 78 and breast cancer risk, 26, 170, 176-177 and chromosome aberrations, 57 defined, 374 and dose-response relationship, 44, 55, 73, 74, 75-76 and hypersensitivity to radiation, 55 kinetics, 75-76 and leukemia risk, 73 and lung cancer risk, 176 and mutagenesis, 57 and mutation rates, 99 and tumorigenesis, 68, 73, 75-76, 78-79, 182 Dose rate and chromosome aberrations, 24 defined, 374 and dose-response relationship, 73, 74 extrapolation from high to low dose, 50 and mutation rate, 100 n.1 in radiotherapy patients, 156-157 and RBE, 24 reduction factor, 100 n.1, 116, 130-131 and tumorigenesis, 73, 74 Dose-rate effect cell cycle phase and, 49-50, 55 defined, 374 DNA repair defects, 49, 56 inverse, 49-50, 55, 57, 60 life shortening, 77 protracted dose distinguished from, 77

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Dose-rate effectiveness factor (DREF) for solid tumors, 146 Dose-response relationships. See also Radiosensitivity adaptive response and, 45, 50-53, 62, 89 animal models, 73-75, 89, 245, 246, 249, 255, 256 assessment of, 139, 140 atomic bomb survivors, 6, 24, 45, 68, 72, 137, 140, 142, 143, 144, 145-146, 147, 149, 150, 151, 152, 153, 245, 256 Bayesian statistical analysis of, 246-250, 254-258 benign neoplasms, 151 biophysical modeling, 45, 139, 246 bone cancer, 74, 75, 201 breast cancer, 74, 76, 86, 149, 157-158, 159, 160, 163, 168, 170, 172, 176, 178-180 bystander effect and, 45, 53, 54-55 cancer mortality, 145 for cancer-risk assessment model, 245-246, 262, 269, 274 cell cycle phase and, 45, 50 cell killing/lethality, 55-57, 75, 78 Chernobyl accident and, 224, 225, 226-227 in children, 10, 161, 162, 168, 169 chromosome aberrations, 24, 25, 45-46, 57-59, 60-61, 73, 74, 256, 257 chronic exposure, 43 control population, 43 DDREF and, 44-45, 60, 246-250, 254-258 DNA damage and response, 31, 73, 246-247 dose fractionation and, 44, 55, 73, 74, 75-76 dose rate and, 73, 74 environmental radiation exposures, 224-225, 233, 234, 235 in epidemiological studies, 132, 137, 139, 140, 189, 208, 245, 246 extrapolating from high dose to low dose, 44-45 general aspects, 43-45, 73 genomic instability and, 45, 46, 48, 49, 60-61 hypersensitivity to radiation and, 55-57 for internally deposited radionuclides, 43, 276 iodine-131 exposure, 235, 276 LET of radiation and, 9, 24, 43, 45, 126, 158, 245 leukemia, 71, 72, 73-74, 76, 77, 142, 144, 157, 158, 160, 161, 163-164, 165, 183, 184, 245, 264, 295 life shortening, 76-77, 89, 249, 255, 257, 258 linear, 13, 47, 60, 62, 73, 74, 77, 137, 201, 246, 247, 250, 264, 269, 299 linear no-threshold, 246 linear-quadratic, 7, 24, 43-44, 47, 74, 201, 247-248, 250, 255, 257, 274, 280 liver cancer, 150, 201 at low doses, 10, 43-45, 57-62, 73 lung cancer, 74, 76, 158, 160, 163, 201, 255, 262 in lymphocyte assays, 57, 58, 60 lymphoma, 73, 74, 77, 78, 151 maxiumum likelihood estimates, 250 modifying variables, 264-266 mouse studies at low doses, 58, 60, 73-75, 76, 78, 126 mutations, 47, 50, 57, 59-60, 61, 73, 108, 113, 114, 245, 246 noncancer mortality, 152, 153 occupational exposures, 189 ovarian cancer, 12, 50 quadratic, 74 radiotherapy-related cancers, 157-170 sex differences, 73, 74 signal transduction pathways and, 62 single-tracks with repair factor, 44-45 skin cancer, 74, 76, 151, 245 solid tumors, 74-75, 142, 144, 145-146, 201, 245, 298 temporal relationships, 45, 50, 60, 61-62, 68, 70, 73-77, 245-246 threshold model, 12, 74-75 thyroid cancer, 149, 160, 162, 167, 168, 169, 182, 215, 224, 225, 276 thyroid diseases, 153 translocations, 57, 58, 60, 61 in tumorigenesis, 12, 45, 50, 55, 59, 60, 61-62, 68, 73-77, 84, 89, 140, 245-246 in tumor-suppressor gene disorders, 84 uncertainties in, 246 X-rays, 49, 56, 61, 62 Dosimeters, personal, 189, 193-194, 201 Dosimetry of ionizing radiation. See also Microdosimetry ankylosing spondylitis cohort, 164, 165 atomic bomb survivors, 6, 9, 10, 20, 24, 27, 72, 129, 134, 139, 141, 142-143, 144 and breast cancer, 159, 178-180 and cancer risk assessment, 241, 266, 268, 269 cervical cancer treatment cohort, 26, 157 Chernobyl accident, 114, 128, 129, 202, 203, 216-223, 224 defined, 374 diagnostic radiation, 155, 156, 170, 176 DS02 system, 27, 142, 269, 285, 296 DS86 system, 27, 142, 285 fallout from nuclear weapons testing, 212, 213, 214 fluoroscopy studies, 170, 176 natural background radiation, 228 neutron component, 27, 143-144 nuclear-facility-related population exposures, 209-211, 212, 213, 214, 229-232 nuclear industry workers, 60, 138-139, 190, 191, 192, 193, 198-199, 201, 202, 203, 231, 233, 290 postpartum mastitis study, 163 radiotherapy recipients, 164, 165 uncertainties in, 3, 14, 128, 129, 139, 142, 169, 198-199, 233, 241, 266, 285 Doubling dose acute, 60, 122 advances in methodology, 94-101, 119, 122-124 atomic bomb survivor data, 7, 8, 118, 124, 130-131, 252 baseline frequencies of genetic diseases, 94-96, 115 basis for, 8, 96, 122-124 BEAR Committee estimates, 96, 123 BEIR I estimates, 96, 97, 118, 122, 123 BEIR III estimates, 118, 122-124 BEIR V estimates, 12, 94-96, 100 n.1, 115, 118, 123, 124 children of atomic bomb survivors, 130-131 chromosomal diseases, 96 chronic multifactorial diseases, 12, 115, 119 defined, 8, 93, 111 dose rate and, 130-131 end points, 122, 123, 124, 130-131 equation, 8, 101-102, 115 estimation, 8, 93-94, 97-101, 113, 115 ESTR mutations, 126 extrapolation from mice to humans, 96-97, 109-111, 252 first-generation mortality and, 130 gametic, 130 Mendelian diseases, 12, 94-95, 115 minimum, 130 mouse vs human mutation rates, 12, 96-101, 113, 119, 122-124 multifactorial diseases, 95-96 mutation component, 8, 101-105, 113, 117 in nuclear test site populations, 128 radiation-induced mutation rates, 99, 101, 119 reciprocal, 93 spontaneous mutation rates, 8, 96-101, 119, 122, 123 uncertainties, 98-99, 130, 131 UNSCEAR estimates, 96, 122, 123, 124 zygotic, 96, 102, 113 Down’s syndrome, 93, 216, 244 Dpc4 gene, 69 Drosophila melanogaster, 53, 91 Duchenne’s muscular dystrophy, 93 Duodenal ulcer, 153 E Edison, Thomas, 2 Effective dose background radiation worldwide, 43 defined, 374 by source of radiation, 22-24 Electricité de France, 191, 192, 197 Electromagnetic radiations. See Gamma rays; X- rays Electrons binding energy, 20 hydrated, 29-30, 54 ionization of water, 20, 21, 29-30 LET, 19, 20 penetration depth, 21 secondary, 27, 29, 31 Endocrine glands, cancer of, 168 Endometrial carcinoma, 67, 80, 86 Energy transfer process biological damage process, 20 direct effects, 26 indirect effects, 29-30 of low-LET radiation, 20-21 Environmental radiation exposures from atmospheric releases, 212-215 cancer incidence and/or mortality, 209-212 case control studies, 211-212, 224-225, 229, 230, 233, 235

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 cesium-137, 215 Chernobyl accident, 215-228, 234-235, 236 children, 208, 209-210, 211, 212, 213, 215-226, 229, 233, 234, 235-238 cohort studies, 212, 213-214, 229, 231-232, 235 congenital defects, 211, 229, 230, 232, 233, 235 dose-response relationships, 224-225, 233, 234, 235 ecologic studies, 208-211, 212, 215, 216-223, 228-229, 235, 236-237 fallout from weapons tests, 212-215, 234, 235 iodine-131, 215, 233-236 and leukemia, 209, 210, 211, 212, 214, 216-222, 226-227, 228-229, 230, 231, 232, 233, 235 limitations and weaknesses of studies, 207-208, 233, 235 and lymphoma, 209, 217, 228-229, 230, 231 natural background, 3, 4, 8, 31, 43, 209, 228, 236-237 nuclear facility proximity and, 208-212, 229, 230, 233, 234, 235-236 parental preconception, 211, 212, 215, 228-233, 235, 237 and reproductive outcomes, 211, 229, 231, 232, 233 surrogates for, 207 Three Mile Island accident, 208, 209, 211 and thyroid cancer, 215-226, 234, 236 uranium mines, 211 Epidemiological studies. See also specific cohorts analysis of data, 136-139 assessment of associations, 132-133, 139-140 BEIR V principal environmental studies, 208, 209-214 bias, 132, 133, 135-136, 139, 140, 152, 173, 187, 208 Bradford Hill criteria, 140 breast cancer, 24-26, 157 case control, 133, 134-135, 136, 148, 172, 190, 207, 208 childhood cancer, 173, 208 cohort, 133, 134, 135, 136, 173, 207, 208 comparability in study design, 133, 135-136, 241 confounding, 133, 136, 138, 141, 199-201, 207, 240 control group, 134, 136, 204 data collection, 133-136, 208 defined, 132, 374 descriptive, 207, 208 design issues, 135-136, 187, 198, 207-208, 287 dose-response relationships, 132, 137, 139, 140, 189, 208, 245, 246 ecologic design, 10, 207, 208, 215, 216-223, 226 exposure assessment, 134-135, 137, 139, 193-194, 207 extrapolation of risks from, 240-241 high-dose studies, 139 hybrid (“nested”), 135, 148, 190 interpretation of data, 139-140, 141 of LET-related risks, 24-26 linear relative risk model, 137, 138-139 measurement errors, 139, 266 measures of association, 132, 137 meta-analyses, 139-140, 268 nuclear industry workers, 189, 190-193 pooled analyses of data, 169, 180, 181, 243, 268-269 randomized intervention trials, 133-134 retinoblastoma, 84 statistical power, 136, 189, 204, 208, 241, 245 tools of statistical inference, 137-138 types, 133 uncertainty in, 133, 207, 208, 265 Epidermal growth factor receptor (EGFR), 55 Equivalent dose, defined, 374 Escherichia coli, 36 Esophageal cancer, 147, 148, 149, 164, 170, 215, 269, 282, 294 Ethylnitrosourea (ENU), 69 Etoposide, 130 age at exposure and, 149 European Childhood Leukemia-Lymphoma Incidence Study, 226 Excess absolute risk (EAR), 269, 270, 271, 272, 273, 274, 275, 276, 277 age at exposure, 298, 301 application, 137, 143, 240-241 breast cancer, 12, 25, 26, 149, 168, 243, 287 comparison of alternative models, 300 defined, 132, 137, 143, 374 leukemia, 144, 307 linear dose-response function, 299 parametric model, 306 model fitting, 296, 299, 304-306 modeling, 143, 285-286 site-specific cancer in atomic bomb survivors, 147, 149, 304-306 solid cancer mortality, 145 tumorigenic radiosensitivity, 84 uncertainty in, 285-286 Excess relative risk (ERR), 144, 268, 269, 271, 272, 273, 274, 275, 276, 277 age at exposure and, 148, 285-286, 296, 297-298, 299, 300, 301 application, 137, 143, 240 bias and, 152 breast cancer, 12, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244 coherence of BEIR VII estimates with other estimates, 287-288 comparison of alternative models, 300 defined, 132, 137, 143 n.3, 374 follow-up period and, 297 in heritable retinoblastoma patients, 84 leukemia, 12, 295, 307-308 linear dose-response function, 299 liver cancer, 148, 301, 302 lung cancer, 12, 148, 150, 159 model fitting, 296, 299-301 excess relative risk, 132, 143, 285-286 for radioepidemiological tables, 306 RERF, 301 sex-specific, 287, 301 site-specific cancer in atomic bomb survivors, 147-150 site-specific cancers, 303-304 skin cancer, 148 solid cancer mortality, 145 statistical precision, 137-138 stomach cancer, 12, 287, 288, 289, 301-302 stratified baseline risks, 299 thyroid cancer, 12 uncertainty in, 285-286 Expanded simple tandem repeat (ESTR) loci, 113-114 Experimental studies defined, 133 potential disease phenotypes, 112-113 RBE of neutrons, 28-29 spontaneous vs. induced mutations, 124-125 Exposure to ionizing radiation. See also Dosimetry of ionizing radiation; Environmental radiation exposures; Low doses; Occupational radiation exposure; Protracted exposure annual worldwide, from natural sources, 2, 3, 4 atomic bomb survivors, 6, 9, 129, 139, 141 chronic, 11, 43, 56, 68, 129, 280 CT scans, 4-5 defined, 374 factors affecting, 4 high-dose, 4, 9, 141 hypoxic conditions, 34 limits, 5, 43 misclassification, 139, 207 priming dose, 51-53, 55, 78, 251 scenarios, 4-6 surrogate indicators, 207, 208 uncertainties in data, 3, 139, 174 U.S. population, 3-4 whole body scans, 4-5, 141 Extrapolation of data from animals to humans, 73, 96-98, 109-111, 114, 115, 252 BEIR V report, 115 cross-population, 85, 88, 240-245, 253-254, 265, 266, 275-276, 278-281, 284, 285, 286, 292 from high dose to low dose, 9, 29, 44, 50, 54, 62, 146, 247, 296 from in vitro to in vivo transformation systems, 52, 53 Moolgavkar and Knudson two-stage clonal expansion model, 241, 253-254 postirradiation cancer mechanisms and, 241 F FA-A to FA-C genes, 80 Fabry’s disease, 93 Fallout. See Nuclear weapons testing Familial adenomatus polyposis, 67, 80, 82, 83, 98 Familial hypercholesterolemia, 98, 125 Fanconi’s anemia, 80 Fbxw7 gene, 69 FEN-1 structure-specific nuclease, 32, 33, 38

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Fenton oxidants, 30 Fernald facility, 191, 200 Fetal exposure to radiation atomic bomb survivors, 151 and cancer in childhood, 6 IEER issues, 330 and mental retardation, 1 Fifteen-Country Workers Study, 336 Finite-locus threshold model, 105-108, 124 Fluorescence in situ hybridization (FISH) method of chromosome painting, 45-46, 57 Fluoroscopy and breast cancer, 26, 170, 176, 177, 180, 243 Canadian epidemiological study, 176, 287 dosimetry, 170, 176 and lung cancer, 174, 175, 176, 288, 289 Massachusetts tuberculosis cohort, 170-171, 174, 176, 243, 273, 287, 292 and skin cancer, 2 14-3-3 proteins, 39 Free radicals, DNA damage from, 19, 29-30, 239 French Commissariat a l’Energie Atomique, 28, 190 G GADD45 gene, 39 Gall bladder cancer, 147, 148, 149, 269 Gamma rays bystander effects, 54-55 cancer risk estimates, 276 carcinogenesis, 24-26, 28 cobalt-60, 19 n.1, 21, 22, 24 damage mechanisms, 26-27 DDREF, 61 defined, 374 dose-rate effect, 28 dosimetry for atomic bomb survivors, 6, 142 environmental exposures, 212 extrapolation to X-ray exposures, 24 high-energy, 24 mutations in mice from, 126 occupational exposures, 204 photon energies, 19, 20, 21, 22, 24, 276 RBE, 21, 22, 24, 25, 28, 126, 276 signal transduction study, 56 terrestrial, 30 Gap junctions, 39, 54, 55 Gastric ulcer, 153, 241 Gastrointestinal cancers, 218 Gene amplification, 47, 49, 72 Gene transcription, 55, 113 Gene-environment interactions, 12, 86, 87, 88 Genes. See also specific genes antibody, 34 autosomal recessive disorders, 80 basic concepts, 327 breast cancer, 67, 79, 80, 82, 83, 84, 85-86, 243 caretaker, 67 checkpoint kinase, 86 deletions, 11, 58, 61, 66, 67, 86, 109, 110, 111, 112, 119, 124, 125 DNA repair, 36, 37, 39, 40, 42, 71, 86, 87-88 epigenetic silencing events, 66, 67 functional polymorphisms, 12, 86-88, 113, 114 gatekeeper, 66-67, 69, 81 haploinsufficiency, 125 human counterparts in mice, 98-99 interactions (epistasis), 12, 70, 108 low-penetrance, 85-88 oxidative damage resistance, 40-42 proto-oncogenes, 81-82 radiation resistance, 30, 40-42 radiation-responsive, 39 recoverability of induced mutations in live births, 109-111, 124, 125 tumor-supressor, 39, 65, 66, 69, 80, 80, 81 X-linked HPRT, 47, 54 Genetic diseases. See also Genetic susceptibility to cancer; specific diseases absolute risk, 110 autosomal dominant, 79, 80, 81, 92, 94, 95, 96, 97-98, 101, 102, 103-105, 110, 112, 115, 116, 117, 125 autosomal recessive, 79, 80, 81, 92-93, 94-95, 96, 101, 104, 105, 110-111, 115, 117-118 baseline frequencies, 12, 92, 94-95, 96, 115, 117-118 basic concepts, 328 chromosomal, 93, 96, 115, 119 chronic, 111, 115, 116, 119 congenital, 93, 95, 105-106, 112, 115, 117, 119 defined, 92 experimental data, 112-113 frequency, 105 inborn errors of metabolisms, 113 marker, 125 Mendelian, 92-93, 94-95, 96, 98, 105, 111, 112, 113, 115, 119 MIM maps, 125 minisatellite polymorphisms and, 113, 114 multifactorial, 8, 93, 95, 96, 101, 112, 115, 117, 119 multisystem developmental abnormalities, 12, 112 mutation component, 98, 101-105, 117 potential phenotypes, 111-113 PRCF estimates, 110-111 prevalence, 80, 96, 98, 110 “radiation-inducible,” 92 risk estimation by class of, 94, 115, 116 spontaneous mutation rates, 97-98, 109 sporadic cases, 108 UNSCEAR estimates, 94-95, 96 X-linked, 92, 93, 94, 95, 96, 97, 98, 101, 104-105, 110, 115, 116, 125 Genetic effects of radiation. See also Chromosome aberrations; DNA damage; Mutations animal studies, 12, 68-70, 73, 82-83, 92 background data from humans, 8 basic concepts, 328 BEIR I estimates, 94 cardiovascular disease, 95, 96 in children, 8-9, 68, 114, 118, 161 detection, 8 disease liability concept, 107, 120-121 germ-cell mutations at ESTR loci and, 113-114, 125-130 heritability concept, 121-122 at human minisatellite loci, 126, 128-130 indicators of risk, 8, 118 models of multifactorial diseases, 120-122, 252 multifactorial threshold model, 120-121, 252 Genetic risk assessment. See also Mutation component of genetic diseases advances since BEIR V, 115-116 in atomic bomb survivors, 8-9, 91, 92, 114, 115, 118, 131, 252 autosomal dominant disorders, 94, 111, 115, 116, 117 autosomal recessive diseases, 94, 112, 115 back calculation, 94, 117 baseline disease frequencies, 12, 94-96, 115, 117, 252 bases for, 8, 96, 115-116 BEIR III estimates, 94-95 BEIR V estimates, 12, 94-95, 96, 115-116, 117-118, 252 calculations, 109, 115, 116 chromosomal diseases, 115, 117 chronic multifactorial diseases, 115, 116, 117 by class of disease, 94, 117 congenital abnormalities, 115, 116, 117, 120 current estimates, 116, 118-120 DDREF and, 92, 246 direct method, 8, 112 doubling dose method, 8, 12, 93-101, 102, 111, 115, 117, 118, 119, 252 endpoints, 118, 130, 131 equilibrium effects, 94, 117 extrapolation of animal data to humans, 96-97, 109-111, 114 first postradiation generation, 94, 116, 117, 118 framework, 92 germ cell stages and, 92 goal, 92 indirect method, 8, 93-94 methods, 91, 92 mouse data, 92, 96-97, 98-101, 109-111, 112-113, 114, 115-116, 252 mutation component, 12, 81, 94, 101-113, 115, 116, 117, 119, 252 overlap in estimates, 119-120 potential recoverability correction factor, 12, 109-110, 115, 119, 252 reconciliation of present and past estimates, 117, 118 reproductive outcomes, 252 second-generation progeny, 116 sex differences, 119, 120 spontaneous mutations, 8, 96-101 UNSCEAR estimates, 92, 94, 95, 96, 109, 111, 112, 115, 118 X-linked disorders, 94, 111, 115, 116, 117 Genetic susceptibility to cancer. See also Radiosensitivity; Tumorigenesis, radiation induced age of onset in carriers, 81 alpha particles and, 53, 87 animal studies, 68-70, 71, 73, 82-83, 87-88, 89 autosomal dominant disorders, 66, 79-81, 85

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 autosomal recessive disorders, 79, 80, 85 breast cancer, 67, 79, 80, 82, 83, 84, 85-86, 87-88, 103, 243 and cancer risk assessment, 85-87, 88, 241, 251 cancer-prone human disorders, 79-81, 85 cellular mechanisms, 79, 81-82 children, 161 colonic and other neoplasms, 66, 67, 79, 80, 86-87 DNA repair defects and, 71, 79-81, 87 genes of low penetrance and, 85-88 heritable radiosensitivity and, 82-85 human data on, 83-87 leukemia, 80 low-penetrance genes, 85-89 lymphoma, 80 mutations, 66-67, 73, 81, 113 population modeling, 85, 88 proto-oncogenes and, 79, 80, 81-82 risk modeling, 81-82, 85, 86, 88, 120-122, 251 secondary cancer in radiotherapy patients, 161 skin cancer, 79, 80 species variation in, 73 spontaneously arising human tumors, 66-67 strengths and weaknesses of current estimates, 118-120 thyroid cancer, 80, 81-82, 244, 246 tumor suppressor genes and, 79, 80, 81 twin studies, 88 to virally associated neoplasia, 79 X-linked disorders, 79 Genomic instability, radiation-induced, 11, 43 alpha particles and, 70, 71 apoptosis and, 48-49 in bone marrow cells, 72 bystander effects, 54, 55, 70 and cancer risk assessment, 251 cell cycle effects, 49, 113 in CHO cells, 58 chromatid instability, 70-73 chromosomal aberrations and, 46, 47-48, 54, 58, 59, 60-61, 70, 251 defined, 47 delayed, in somatic cells, 127 DNA repair defects and, 48, 49, 72 dose-response relationship, 45, 46, 48, 49, 60-61 frequencies, 47-48, 61 gene mutations and, 61, 66, 68, 70, 87, 88, 113, 126-127 guardian-of-the-genome hypothesis, 48-49 in hematopoietic cells, 70-71 hypersensitivity to radiation and, 57, 71 manifestations, 47, 54, 55, 57, 58, 70 at minisatellite and ESTR loci, 113, 126-127 modeling, 251 in mouse mammary epithelial cells, 71-73 in mouse melanocytes, 58 persistent, 46 reactive oxygen species and, 48 RBE, 71 target and lesions resulting in, 48 telomere-associated, 48, 71-73, 251 transgenerational, 127 and tumorigenesis, 39, 46, 48-49, 65, 67, 69, 70-73, 78, 251 in zygotes, 127 Genotype, and adaptive response, 53 Germ cells. See also Genetic diseases; Genetic susceptibility to cancer defined, 374 ESTR loci, 113-114, 125-130 minisatellite loci, 113-114, 128-129 mutations, 6, 8, 81, 97, 109, 113-114, 125-130 polymorphisms, 87 stages and radiation conditions of relevance, 92 German Childhood Cancer Registry, 226 Gliomas, 55, 82, 166, 168 Glycosylases, 32, 34, 35, 42 Goiter, 218, 226, 244 Grave’s disease, 165, 166 Growth and development effects animal studies, 115 DNA repair defects, 34 human studies, 8 mental deficiency, 112 multisystem abnormalities, 112, 115 Guardian-of-the-genome hypothesis, 48-49 H H2AX histone protein, 31, 36, 50 Hamsters Chinese hamster ovary (CHO) cells, 48, 55, 58, 59, 61 DNA repair rates in Chinese hamster V79 cells, 52 malignant transformation in embryo cells, 59, 61 mutation studies, 59 Hanford Site, 135, 190, 191, 192, 193, 197, 199, 200, 213, 215, 230, 234, 235, 276 HAP1, 32 Hardy-Weinberg equilibrium, 102 Health end point data, 76-77, 142 Heart disease. See Cardiovascular disease Heat shock-related proteins, 52-53 Heavy metal exposures, 128, 242 Helicobacter pylori infection, 241-242, 302 Hemangiosarcomas, 150 Hematopoietic cells, chromatid instability in, 70-71 Hemochromatosis, 93 Hepatitis, 150, 153, 242, 302 Hepatoblastoma, 150 Hepatocellular carcinomas, 150, 242 Heritable genetic effects in humans. See Genetic diseases; Genetic effects of radiation; Genetic risk assessment; Genetic susceptibility to cancer High-LET radiation. See also Alpha particles; Neutrons bystander effects, 53-54 carcinogenesis, 49 chromosome aberrations, 45 damage mechanisms, 2, 19, 36, 45 defined, 375 dose units, xi, 2 dose-rate effects, xi epidemiological studies, 198-199 mutation rates, 9, 126 physics and dosimetry, 19, 198-199 RBE, 31, 126 sources, 4 Hiroshima Tumor Registry, 268 Histones, 30, 31 hMre11/hRad50/Nbs1 DNA-binding and exonuclease complex, 35, 36, 39 Hodgkin’s disease, 12, 130, 151, 158-159, 174, 175, 176, 177, 242-243 Hormesis, 11 adaptive response, 333 animal studies, 334 cell studies, 333 and epidemiology, 334-335 life span data, 334 theoretical considerations, 332 tumor incidence data, 334 Hormones and breast cancer, 76, 157-158, 159, 168, 169, 241, 243 and thyroid cancer, 244 and tumorigenesis, 75 HPRT gene, 44-45, 47, 51, 53, 54, 58, 61 hRad51 protein, 35, 36 hRad52 protein, 35, 36 hRad54 protein, 35 HRAS1 gene, 113 HSP70 proteins, 52-53 HSP90 proteins, 52 HTLV-1, 244 Human cell lines/systems chromosomal instability in diploid fibroblasts, 72 fibroblasts, 51, 54, 55, 57, 58, 72 Hela hybrid system, 52, 59, 62 human-hamster hybrid, 51, 72 hypersensitivity to killing, 56 immortalized, 52, 58 keratinocytes, 54-55 malignant transformation, 59, 62 MCF-7:W58 breast cancer, 56 mutagenesis in lymphoblastoid cells, 51, 59-60 myeloid tumor, 56 oocyte radiosensitivity, 99 TK6 lymphoblasts, 58, 59-60, 61 Human studies. See also Epidemiological studies bone cancer, 84 genomic instability, 71 mutations at minisatellite loci, 113, 114, 128-130 Hungarian congenital disease population, 95 Huntington’s disease, 98, 125 Hydrogen peroxide, 29, 30, 31, 40, 41, 42, 50, 53 8-Hydroxyguanine, 31 Hydroxyl radical bystander effect and, 54 damage mechanisms, 29-30 production during energy transfer processes, 31 Hyperparathyroidism, 151, 153

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Hypersensitivity to radiation at low doses, 11, 32, 45, 47, 51, 55-57, 71, 82, 239 Hypertension, 93, 95, 111, 153 Hyperthyroidism, 165-166, 169, 182, 185, 226, 234 Hypothyroidism, 226 Hypoxanthine-guanine phosphoribosyl transferase (HGPT) mutation, 44-45 I IDDM2 gene, 113 Immune disorders, virally associated neoplasia, 79 Immune response, 66-67 Immunodeficiency, 34, 80 Immunoglobulin, 34, 66 Immunologic rearrangement, 35 Immunophilins, 52 In vitro assays. See also; Human cell lines/systems; Lymphocytes; individual animal species adaptive response in mammalian cells, 51, 52, 62 bystander effect in, 53, 54-55 CHO cells, 48, 58, 61 chromatid instability in bone marrow cells, 71 chromosome aberrations in human cells, 24, 53, 58, 61, 72 defined, 375 extrapolation to in vivo transformation systems, 52, 57 genomic instability, 58 of LET-related risks, 24 M5S mouse embryonic skin cells, 52 malignant transformation, 51-52, 61-62 priming dose, 52 RBE, 24 somatic mutagenesis, 69 trypsinization and replating, 52, 62 Inelastic scattering, 20 Infertility, hormonal, 164 Institut Gustave Roussy, 160, 161, 169 Institute for Energy and Environmental Research, issues raised by, 330-331 Institute of Haematology and Blood Transfusology (Belarus), 203 Internally deposited radionuclides. See also Iodine-131; other specific radionuclides alpha particles, 199-200 cancer risk estimates, 200, 276 Chernobyl accident and, 276 dose estimates, 3, 4 dose-response relationships, 43, 276 and lung cancer, 200 measurement problems, 199-200 naturally occurring, 30, 43 nuclear industry worker exposure, 190, 199-200 and prostate cancer, 200 International Agency for Research on Cancer, 336 International Cervical Cancer Survivor Study, 181 International Childhood Cancer Survivor Study, 181 International Classification of Diseases, 95 International Commission on Radiation Units and Measurements, 22, 375 International Commission on Radiological Protection, 22, 81, 85, 103, 105, 109, 124, 165, 197, 246, 274, 282, 283, 292-293, 294, 297, 375 Intestinal carcinoma, 69, 70, 87, 88, 166 Iodine deficiency, 244 Iodine-131 adaptive response to, 51 childhood exposure, 68, 169, 173, 215 diagnostic exposures, 171, 173, 234 dose-response relationship, 235, 276 environmental exposures, 68, 209, 214, 215, 233-235 radiotherapy-related risks, 161, 165-166, 171, 182, 234 and salivary gland tumors, 165 thyroid cancer, 68, 161, 165, 171, 182, 214, 215-226, 233-235, 276 Iododeoxyuridine (125Idu), 48 Ionizing radiation. See also Alpha particles; Beta particles; Exposure to ionizing radiation; Gamma rays; High-LET radiation; Low-LET radiation; Natural background radiation; Neutrons; X-rays background, 30-31 chemical aspects, 29-32 damage mechanisms, 6, 26-27, 29-30, 40-42, 239 defined, 1, 375 detection, 2 direct effects, 19, 29-30, 31 discovery, 1-2 indirect effects, 19, 29-30 late effects, 11 low doses defined, 2 photon spectral distributions, 20-22 physical aspects, 19-29 sources, 3-6, 11 track structure, 21, 26-27, 29, 55, 62 types, xi, 2, 19-20; see also Gamma rays; X rays U.S. population exposure, 3-4 Iron-59, 200 I-SceI endonuclease, 48 Ischemic heart disease, 95, 153 Israel Tinea Capitis Study, 68, 155, 156, 166-167, 181, 182, 183, 273, 292 J Japanese nuclear workers, 198 Jaslovske power plant, 197 Juvenile osteocondrosis, 95 K Kerma doses, 144, 375 Kidney carcinoma, 66, 149, 161, 164, 166, 227, 228, 269, 282, 293, 294 Ku-70, 35, 42, 56 Ku-80, 35, 42, 56 L Laboratory animals. See Animal studies; specific animals Late Effects Study Group, 161, 162 Latent health effects RBE of neutron doses and, 27 Lead, 200 LET. See Linear energy transfer Leukemia acute lymphatic, 144, 210, 218, 226 acute myelogenous, 68-69, 144, 153, 164, 227 acute nonlymphocytic, 67, 162 adult T-cell, 144, 244 age factors and, 144, 264, 288 alpha particles and, 71 analysis of human data, 296, 307-308 animal studies, 68-70, 71, 72, 73-74, 87 in ankylosing spondylitis cohort, 164, 165, 183, 289 in atomic bomb survivors, 68, 72, 142, 143, 144, 153, 172, 244, 245, 269, 307-308 BEIR V model, 246, 282, 283, 292 breast cancer survivors, 159-160 caretaker gene, 67 in cervical cancer survivors, 157, 158, 183, 289 chemotherapy-related, 86, 160, 244 Chernobyl accident and, 203-204, 216-222, 225-227 children, 84, 161, 168, 172, 209, 210, 211, 212, 214, 216-222, 226-227, 233, 244 chromosome aberrations and, 65, 68-69, 72, 74 chronic lymphocytic, 157, 159-160, 162, 212, 244, 283, 307 chronic myelogenous, 144, 171 coherence of BEIR VII estimates with other studies, 288, 289, 294 deaths, 144 diagnostic irradiation and, 170, 171, 172 dose fractionation and, 73 dose-response relationship, 71, 72, 73-74, 76, 77, 142, 144, 157, 158, 160, 161, 163-164, 165, 183, 184, 245, 264, 295 environmental exposures and, 209, 210, 211, 212, 214, 216-222, 226-227, 228-229, 233, 244 EPA model, 282 etiology, 243 excess relative risk, 12, 295, 307-309 frequencies, 77 genetic susceptibility, 80, 86, 87 human data, 72 ICRP model, 282 in infants, 218-221, 226 in utero exposures and, 172 incidence, 244, 284 initiation mechanisms, 66-67, 68, 74 internally deposited radionuclides and, 200 latent, 68, 72 lymphocytic (nonacute), 67, 164 medical-exposure-related risks, 12, 289-290 misclassification of cause of death, 153 models, 144, 246, 264, 273-274, 307-308 monocytic, 171

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 mortality, 189, 196, 197 myeloid, 71, 72, 73-74, 76 neutron RBE and, 29, 143 NIH model, 295, 308 in nuclear industry workers, 14, 190, 191, 196, 197, 198, 199, 200, 201, 202-204, 275, 288 nuclear weapons testing and, 214 quantitative studies, 73-74 in radiologists and radiologic technologists, 189, 204, 205 radiosensitivity of bone marrow, 173 in radiotherapy recipients, 84, 157, 158, 160-161, 162, 163-164, 165, 166, 168, 183-185 registry data, 142 risk assessment, 143, 144, 245, 246, 273-274, 285, 295, 296, 307-308 risk estimates, 173, 183-185, 277, 278, 280-282, 284, 289-290, 294, 307-308 risk factors, 244 sex differences, 73, 144, 284 in tinea capitis cohort, 166, 183 temporal distribution, 144 uncertainties in risk, 284, 285 UNSCEAR model, 282, 294 X-rays and, 71 lex gene, 36, 37 Life expectancy, 153-154, 161 Life shortening studies in atomic bomb survivors, 153-154 and DDREF, 246 dose-response relationship, 76-77, 89, 153, 249, 255, 257, 258 as proxy for mortality, 28-29 wasted radiation concept, 77 Life span, and paternal effect for mutations, 97 Life Span Study, 9, 12-13, 26, 141-154, 246-250, 267-268, 285-308, 375. See also Atomic bomb survivors Li-Fraumeni syndrome, 79, 80, 81, 82, 83, 84 Linde facility, 190 Linear energy transfer (LET). See also High-LET radiation; Low-LET radiation; Restricted LET and carcinogenesis, 24-26, 49 and chromosome aberrations, 45 consistency with other studies, 57 defined, 19, 375 and DNA damage, 20, 26-27, 31, 245 dose average, 19 n.1, 22, 23 and dose-response relationship, 9, 24, 43 in vitro studies, 24 microdosimetric analogue, 22, 23 protons and electrons in water, 20 as quality-of-radiation measure, 22-24 radioepidemiologic studies, 24-26 RBE variation with, 21 track average, 19 n.1 Linear no-threshold (LNT) model, 9-10 basic assumption, 7 DDREF adjustment, 7 defined, 375 description, 6-8 dose-response relationship, 246 lifetime-risk example, 7-8 Linear relative risk model, 137 applications, 138 equation, 138 statistical inferences, 138-139 Linear-quadratic model, 6 DDREF estimates, 246 defined, 375 dose-response relationship, 7, 24, 43-44, 47, 74, 201, 247-248, 250, 255, 257, 274, 280 for leukemia, 14, 246, 292, 295 RBE derivation, 24, 28 Lineoleic acid 13-hydroperoxide, 40 Lipid peroxidation, 30, 34 Liver cancer age at exposure and, 150 alpha particles and, 68 atomic bomb survivors, 147, 148, 149, 150, 269, 298 baseline lifetime risk estimates, 278 death certificate data, 150 diagnostic irradiation and, 68 dose-response relationship, 150, 201 etiology, 242 excess relative risk, 148, 301, 302 hepatitis antigen status and, 150, 242 human studies, 68 incidence, 298, 303, 305 metastatic, 150 mortality, 298, 304, 306 multiplicative model, 242 risk factors, 241, 242 risk models and estimates, 242, 272, 278, 279, 280, 282, 284, 285, 294, 301, 303-306 Thorotrast exposure and, 150 Liver disease and cirrhosis, 153, 242 Los Alamos National Laboratory, 192, 197 Low doses breast cancer risk, 86 cumulative effects, 53, 155 defined, 2, 11 DNA damage, 31 dose-response relationships, 10, 43-45, 57-62, 73 hyper-radiation sensitivity at, 55-57 neutron RBE at, 28-29 potential for beneficial effects, 10 probability of cell damage, 9-10 protracted exposure, 31 solid tumors, 74 Low-LET radiation. See also Gamma rays; X-rays annual worldwide exposure from natural sources, 2, 3, 4 bystander effects for, 54-55 carcinogenic effects, 245 cell lethality, 55-57 damage mechanisms, 26-27 defined, 375 dose units, xi dose-response relationships, 45, 126, 158, 245 epidemiological studies, 199 in vitro studies, 22, 24 mutation rates, 9 physics and dosimetry, 19, 21, 199 RBE variation with dose rate, 21, 24 sources, 1, 4 track structure, 21, 43-44, 55 Lung cancer. See also Respiratory system cancer additive risk model, 150, 159, 242, 276 adenocarcinomas, 50, 76 age and, 147 age at exposure and, 150, 160 alpha particle exposure and, 242 animal studies, 28, 50, 74, 76, 87 in ankylosing spondylitis cohort, 164, 174 in atomic bomb survivors, 68, 147, 148, 150, 242, 262, 269, 276 baseline lifetime risk estimates, 278 in benign breast disease cohort, 174 in breast cancer survivors, 160, 174, 175 in cervical cancer survivors, 157 chemotherapy and, 159 childhood exposures and, 168, 175 diagnostic irradiation and, 170, 174, 176 dose fractionation and, 176 dose-response relationship, 74, 76, 158, 160, 163, 201, 255, 262 dosimetry, 159, 160 etiology, 242-243 excess relative risk, 12, 148, 150, 159 fluoroscopy and, 174, 175, 176, 288, 289 genetic susceptibility, 86-87 in Hodgkin’s disease cohort, 158, 159, 174, 176, 242-243 incidence, 174, 175, 242, 262, 278, 279, 284, 298, 303, 305 internally deposited radionuclides and, 200 latent, 159 medical-exposure-related risks, 174-176, 288 mortality, 174, 175, 242, 278, 280, 282, 298, 304, 306 multiplicative effects, 158, 159, 176, 242 in nuclear industry workers, 135, 190, 198 in peptic ulcer cohort, 163, 174, 175, 288 in radiologists and radiologic technologists, 204, 205 in radiotherapy-related risks, 157, 158-159, 160, 162, 163, 164, 166, 168, 174, 242, 288 repair kinetics, 76 risk models and assessment, 147, 148, 173, 174-176, 242, 244-245, 272, 275, 278, 279, 280, 282, 284, 288, 294, 303-306 sex differences, 150, 176, 284 in skin hemangioma cohorts, 174, 175, 176 smoking and, 87, 135, 138, 150, 158, 159, 174, 176, 198, 242, 276 uncertainties in risk assessments, 138 in uranium/underground miners, 138, 242 Lymphocytes, 24, 34 adaptive response in, 51, 53 bystander effect, 53 chromosome aberrations, 45, 46, 51, 53, 57, 58, 59, 61, 86 dose-response relationship at low doses, 57, 58, 60 genomic instability, 49, 59 HPRT mutations, 60 immortalized, 57, 58 PHA-stimulated, 59, 61

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Lymphohematopoietic tumors, 67, 71 Lymphoma animal studies, 68, 73, 74, 76, 78 in atomic bomb survivors, 151, 153 cell killing and, 74, 78 in cervical cancer survivors, 157 Chernobyl accident and, 217, 227 children, 209, 210 chromosome aberrations and, 65 diagnostic irradiation and, 171 dose-response relationship, 73, 74, 77, 78, 151 environmental exposures and, 209, 217, 228-229 etiology, 78 frequencies, 77 genetic susceptibility, 80, 87 iodine-131 exposures, 171 misclassification of cause of death, 153 murine, 68-70, 73, 74, 78, 87 initiation mechanisms, 66-67, 68, 69, 70, 73, 74 and intestinal neoplasia, 88 mortality, 151 pathogenesis, 74 in radiologists and radiologic technologists, 204, 205 radiotherapy and, 164 sex differences, 74, 151 target cells, 74 thymic, 12, 68, 73, 74, 76, 78 M Macrophage oxidative bursts, 29 Mallinckrodt facility, 200 Malondialdehyde, 34 Mammary cancer. See also Breast cancer, female adenocarcinomas, 50, 74 bystander effects, 55 chromatid instability and, 71-73 hormones and, 28 in mice, 69, 71-73 neutrons and, 28, 50 in rats, 28 Mammography, 4, 20, 21, 22, 24 Man-made radiation sources, 3-4 U.S. population exposure, 3-4 MAPK, 39 Marfan syndrome, 92, 98 Massachusetts General Hospital, 165 Mastitis patients, radiotherapy-related cancer, 26, 163, 177, 180, 243, 287, 292, 293 Mathematical models. See Models/modeling Mayak plutonium production complex, 57, 190, 201-202, 212, 213, 214, 215, 235, 275, 276 Mayo Clinic, 165 Maximum likelihood principle, 138, 139 MCF-7:W58 cell lines, 56 Medical uses of radiation. See also Diagnostic radiation; Radiotherapy studies adaptive response to, 51 age at exposure, 297 atomic bomb survivor data combined with, 146-147 and breast cancer, 12, 26, 84, 86, 157, 160, 163, 176-180, 287 cancer risk estimates, 12, 26, 173-187, 240, 241, 276, 286-290 and circulatory diseases, 12, 185-187 coherence of BEIR VII model with other studies, 286-290 doses from, 30, 156 epidemiological studies of exposure, 155-156 exposure limits, 43 and leukemia, 12, 183-185, 289-290 and lung cancer, 12, 174-176, 242 noncancer disease risk, 8, 12, 159, 160, 163, 185-187 occupational exposures, 204-205 physician population as surrogate for dose, 329 and RBE, 276 risk modeling, 138, 146-147, 276 sources of, 4-5, 30 and stomach cancer, 185 and thyroid cancer, 180-182, 287 Medulloblastoma, 69, 70, 80 Melanoma, 67, 80, 151, 161, 162, 190 Menadione, 40 Mendelian diseases, 92-93, 94-95 Meningiomas, 80, 166-167, 168 Mental retardation, 1 Mercury, 200 Metropathia hemorrhagica, 164 Michael Reese Hospital, 169, 181, 182 Microarray expression studies, 39, 53 Microdeletion syndromes, 112 Microdosimetry, 22, 23 Microencephaly, 80 Micronuclei, 47, 51, 54, 55 Minisatellite loci, 113-114, 128-130 Mitochondrial electron transport, 49 Mitogen-activated protein kinase (MAPK), 55 MLH1 gene, 67, 80 MLH2 gene, 80 Model fitting AMFIT program, 143, 269, 296 EPICURE software, 138, 143, 269, 296 to epidemiological data, 138, 269 leukemia data, 144 maximum likelihood estimates, 138, 139, 296 preferred risk models, 296-308 for site-specific cancers, 303-307 for solid cancers, 298-302 summing solid cancers, 279-280, 296 Wald method, 138 Models/modeling. See also Cancer risk assessment; Genetic risk assessment; Uncertainties absolute risk, 242, 244, 245, 253-254 adaptive response, 250-251 additive risk, 148, 150, 159, 240, 241, 242, 244-245, 254 age-at-exposure effects, 143, 264, 297-298 applications of, 264-265 Armitage-Doll, 262 atomic bomb survivor data, 143-144, 262, 263, 296-308 BEIR III, 138 BEIR V, 246 biologically based, 147, 262-263 biophysical, 45, 139, 246 breast cancer, 148, 273 bystander effects, 251 data quality and completeness, 265 defined, 375 dose measurement and, 139, 266 dose-response relationship, 45, 73-75, 89, 139, 245, 246, 249, 255, 256, 264-266 empirically based, 263-264 evolutionary population genetic, 105, 106 excess absolute risk, 143, 285-286 excess relative risk, 132, 143, 285-286 extrapolation from high dose to low dose, 9, 29 extrapolation from one population to another, 88, 240-245, 253-254, 266 finite-locus threshold, 105-108, 124 general mutagen model, 262 genetic susceptibility to cancer, 81-82, 85, 86, 88, 120-122, 251 genomic instability, 251 heritable effects of radiation, 92, 120-122, 251 Interactive RadioEpidemiological Program, 295 leukemia risk, 144, 246, 273-274 linear no-threshold, 6-10, 375 linear relative risk, 137, 138-139 linear-quadratic, 6, 43, 246 mathematical, 92, 261-262 medical-use-related risks, 138, 146-147 Moolgavkar-Knudson two-stage clonal expansion model, 241, 253-254, 262 multifactorial threshold model of disease liability, 93, 105, 107, 120-121, 252 multiplicative, 148, 163, 240, 241, 242, 243, 254, 297 multivariate, 138, 265 NCRP review of, 293 parameter estimation, 264, 285-286 parametric, 143, 296, 299 polygenic computational, 86 population, 85, 88, 286 postirradiation cancer mechanisms and choice of, 241 preferred (BEIR VII) model, 6-8, 138, 244, 264, 269-278, 310-312 probability, 260, 265 projections of cancer risk over time, 239-240 relative risk, 25, 26, 137, 138-139, 148, 149, 159, 164, 175, 240, 242, 243, 244, 253 solid cancers (all), 143, 269-271 threshold, 12, 74-75, 105-108, 120-121, 124 thyroid cancer, 273 Moolgavkar-Knudson two-stage clonal expansion model, 241, 253-254, 262 Mortality ankylosing spondylitis cohort, 164, 165 atomic bomb survivors, 130, 131, 141, 142, 143, 144, 145, 147, 151, 152-153, 298-307 cancer, 2, 4-5, 28-29, 68, 76-77, 142, 144, 145, 151, 165, 170, 172, 174, 175, 176, 177, 181, 189, 191, 194-198, 200, 201, 202, 203, 204, 205, 209-212, 242, 243, 298-307

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 dose-response relationships, 145 healthy worker effect, 136 life shortening as proxy for, 28-29 lymphoma, 151 nonneoplastic disease in atomic bomb survivors scans, 141, 152-153 premature, 8 solid cancers, 144, 145 Mound Facility, 191, 192, 197 Mouse/murine studies adaptive response, 51, 52, 53, 55, 78 AKR strain, 78 Apc-deficient genotype, 69, 70, 87 Atm-deficient, 82-83 BALB/c, 71, 74, 76, 127 BRCA-deficient, 82-83 cataracts, 115 C3H 10T1/2 cells, 50, 52, 55, 59, 61-62 C3H/HeN strain, 126 C57BL/6 strain, 71, 127 CBA strains, 71, 73-74, 78, 127 chemotherapy studies, 130 chromatid instability, 71-73 chromosome aberrations, 48, 57, 58, 119 congenital abnormalities, 115, 116, 131 DNA repair, 34, 42 dose-rate reduction factor, 100 n.1 dose-response relationships at low doses, 58, 60, 73-75, 76, 78, 126 doubling dose, 96-97, 98-101, 113 ESTR mutations, 113, 114, 125-127 extrapolation of data to humans, 73, 96-98, 114, 115 gene deletions in melanocytes, 58, 61 genetic effects of radiation, 92, 98-101, 109-111, 112-113, 115-116, 119 genetic models of tumorigenesis, 58, 61, 68-70, 82-83, 87 genome sequencing, 119, 125 genomic instability as gene deletions, 58, 61 Harderian gland tumors, 74 HPRT mutations, 44-45, 58, 60 human counterparts of genes, 98, 99 induced mutation rates, 92, 98-101 intestinal tract cancers, 87 leukemia, 68-70, 72, 73-74 lung cancer, 28, 50, 74, 76, 87 lymphoid neoplasms, 68-70, 73-74, 78 malignant transformation, 59, 61-62 mammary tumors, 50, 71-73, 74, 88 minisatellites, 125-126 ms5S embryonic skin cells, 51, 52 multisystem developmental abnormalities, 112-113 mutation studies, 8, 44-45, 47, 50, 56-57, 58, 60, 92, 98-101, 109-111, 112-113, 126-127, 130 oocyte killing, 24, 75, 98-99, 130 ovarian tumors, 50, 74, 75, 76 quantitative studies, 73-75 radiosensitivity, 42, 56-57 RFM strain, 28, 29, 73-74, 75 skeletal abnormalities, 115 skin cancer, 75, 87 solid tumors, 74-75 spermatogonia mutations, 50, 98 telomere-deficient strains, 48 Trp53-deficient, 78 tumorigenesis, 68-70, 71-75, 82-83 MRE11, 37 Mre11/Rad50/Nbs1, 38 MSH2 gene, 67 Mucoepidermoid carcinoma, 150 Multifactorial diseases, 8 baseline frequencies, 95-96 BEIR V estimates, 95, 96, 115, 117 BEIR VII estimates, 96 cancer as, 81 chronic, 95, 96, 105-113, 115, 117, 119, 124 congenital, 93, 95, 96, 112, 117 defined, 93 doubling dose, 94, 95-96, 101, 115 estimates of risk, 115, 117 examples, 93 familial aggregation studies, 122 genetic basis, 93, 95-96, 124 models, 93, 95, 105-106, 120-122, 124 multisystem developmental abnormalities, 112-113 mutation component, 81, 94, 101, 105-113, 117, 119, 124 potential recoverability correction factor, 119 prevalence, 95 risk estimates, 117, 119 threshold model, 93, 94, 120-121, 124 Multifactorial threshold model of disease liability, 93, 105, 107, 120-121 Multiple dystrophy, 98 Multiple endocrine neoplasia, 80 Multiple exotoses, 98, 125 Multiple myeloma, 151, 164, 171, 204, 205, 214 Multiplicative effects, 148, 150, 163, 240, 241, 242, 243, 254, 297, 376 Mutagenesis adaptive response, 51 alpha particles, 53, 54, 68 apoptosis and, 49 bystander effects, 54 cell cycle phase and 49, 50, 81, 113 in cells hemizygous for autosomal APRT, 46 chromosome aberrations and, 47 DDREF, 246 DNA damage and repair processes and, 47, 65, 246 dose fractionation and, 57 dose-rate effects, 50 dose-response relationship, 47, 50, 57, 59-60, 61, 113 at ESTR loci in mice, 113-114 genetic context, 46 germline, 47, 65, 114 at HPRT gene, 47, 51, 53, 58, 59-60, 61 hypersensitivity to radiation and, 56-57 mechanisms, 27, 46-47, 126 at minisatellite loci in humans, 113-114 radiation quality and, 47 RBE variation with LET, 24, 47 in somatic cells, 46-47, 113, 246 in spermatogonia, 60 target genes, 47 in TK6 human lymphoblastoid cells, 59-60, 61 Mutation component of genetic diseases application, 102 autosomal dominant diseases, 102, 103-105, 111, 115, 116, 119 autosomal recessive diseases, 104, 105, 110-111, 115 BEIR V estimates, 94, 106, 115 chronic multifactorial disease, 105-113, 119 concept, 94 congenital abnormalities, 105-106, 111, 116 defined, 94, 101-102, 111 dose-response relationship, 108, 245 for early postradiation generations, 106, 116 at equilibrium, 94, 106 estimation, 103-113 finite-locus threshold model, 105-107, 108, 111, 124 first-generation increase in mutation rate and, 103, 104, 105, 106-108, 109, 119 gene-gene interactions (epistasis) and, 108 Hardy-Weinberg equilibrium, 102 heritability of liability concept, 105, 106, 107, 111, 121-122, 124 ICRP hybrid model, 105, 109 multisystem developmental abnormalities, 112 murine studies of induced mutations, 109-111, 112-113, 116, 124-125 mutation-selection balance, 94, 102, 103, 105, 106, 107, 109, 117 nonsporadic cases, 103 numerical estimates, 104-105 permanent increase in mutation rate and, 104, 105, 106-109 “phenotypes” of human diseases, 111-113 population genetic concepts, 102 potential recoverability correction factor, 109-110, 111, 125 rationale for, 101-102 spontaneous mutations in humans, 109-111, 124-125 sporadic, 103-104, 108 strengths and weaknesses of, 119 UNSCEAR, 109 X-linked diseases, 104, 105, 111, 115, 116, 119 Mutation rates age and, 97 animal studies extrapolated to humans, 96-98 in atomic bomb survivors, 6, 114, 129, 130-131 calculating rates in mice, 99-100, 119 in children of atomic bomb survivors, 114 in children of Chernobyl inhabitants/cleanup workers, 114, 128, 129-130 dominant disorders, 98, 100 dose fractionation and, 99 in early postradiation generations, 106 effects at equilibrium following permanent increase, 106-109 at ESTRs, 126-127 family size and, 97 in first generation, 105, 106, 108, 129 and fitness of a population, 102 and genetic disease risk in humans, 109-111 in human genes, 97-98

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 mice, 92, 96-101, 109-111, 114, 126 at minisatellite loci, 114, 128-130 parental birth year and, 129 in progeny, 70, 97 sex differences, 96-97, 119, 128 spermatogonial stage, 100, 113 spontaneous, 97-101 X-linked diseases, 98 Mutations. See also Chromosome aberrations; DNA damage; Genetic effects of radiation; Spontaneous mutations animal tumors, 68-70, 96-98 in atomic bomb survivors, 6 autosomal dominant, 98 basic concepts, 327-328 biochemical (null enzyme), 98, 99, 131 broad-sense and narrow-sense heritability and, 121-122 and cell death, 47 Chernobyl accident and, 128-129 complex, 51 congenital abnormalities, 131 defined, 327 deletions, 36, 40, 47, 54, 65, 109 detection, 127, 129-130 dominant negative, 125 dose-response relationship, 47, 57, 59-60, 73, 113, 114, 246 in Drosophila melanogaster, 8 electrophoretic, 131 first generation, 130-131 frequencies, 46-47, 94, 105 gain-of-function, 66, 81, 125 germline, 6, 8, 81, 103, 109; see also Genetic susceptibility to cancer high-penetrance, 81, 85 HPRT, 44-45, 47, 53, 58, 60 human minisatellite loci, 128-129 human tumors, 66-67 indirect, 127 intragenic, 109 lethal, 47 loss-of-function, 66, 67, 81, 125 low-penetrance, 85-88 at minisatellite loci in humans, 113, 114, 128-129 missense or nonsense, 125 mouse studies, 8, 44-45, 47, 50, 56-57, 58, 60, 92, 98-101, 109-111, 112-113, 125-126 multilocus, 46 multisite DNA fingerprinting, 129 point, 46, 66, 125, 131 potentially recoverable, 109-111, 112 radiation-induced tumors, 67-68, 239 recoverability of genes in live births, 109-111, 124, 125 relative risk, 6 reversion, 47 single-gene, 46 somatic, 103, 113 specific-locus, 60, 100 spontaneously arising tumors, 66-67, 239 trinucleotide repeat expansions, 125 Tradescantia, 24 and tumor susceptibility, 66-67, 242 Myelodysplastic syndrome, 153 MYH gene, 67 Myocardial infarction, 153 Myotonic dystrophy, 92 N Nagasaki Tumor Registry, 268 National Council on Radiation Protection and Measurements, 43, 293, 376 National Institutes of Health cancer risk model, 138, 268, 269, 273, 277-278, 293 radioepidemiological tables, 294-296, 299 National Radiological Protection Board, 82, 85, 293 National Registry of Radiation Workers (UK), 14, 190, 193, 195, 196, 197, 198, 200, 230, 290 National Research Council Committee on Atomic Casualties, 91 Committee on the Biological Effects of Atomic Radiation, 91 Committee on the Biological Effects of Radiation, 91; see also BEIR entries Natural background radiation annual effective dose per person worldwide, 2, 3, 4, 30, 43 cancer risk, 7-8, 228 chemical aspects, 30-31 defined, 373 DNA damage, 30-31 dosimetry, 228 ecologic studies, 228 in Great Britain, 228 high-dose exposures, 4 in Kerala, India, 228 low-dose exposures, 4, 8, 31, 43 occupational exposures, 204 sources, 2, 3, 30, 43 uncertainty in estimates, 3, 7 U.S. population exposure, 3 in Yangjiang County, Guangdong Province, China, 228 NBS gene, 80 Nbs1, 36 NBS1, 37 Nephroblastoma, 66, 80 Nervous system benign tumors, 152 cancer of, 148, 149, 151, 152, 171 Neural tube defects, 93 Neurofibromas, 66, 80 Neurofibromatosis, 80, 84, 92, 98 Neutrons animal studies, 28-29, 68, 126 atomic bomb survivors, 20, 27, 142, 143, 146 carcinogenesis, 50 cell cycle effects, 50 cell killing, 28 chromosome aberrations from, 27-28 damage mechanisms in tissues, 19, 27 dose-effect relationship, 28 DS02 dosimetry, 27 DS86 dosimetry, 27, 142 fission-spectrum, 20, 28, 50 high-energy, 19 leukemia, 71 linear dose coefficient, 28 and lymphoma, 68 mutations in mice, 68, 126, 127 occupational exposures, 199, 204 physics, 19 RBE, 20, 27-29, 126, 142, 143, 146, 297 weighting factor for absorbed dose, 296-297 Nevoid basal cell carcinoma syndrome, 80, 82, 83, 84 New York State Postpartum Mastitis Study, 26 NF1 gene, 66, 80, 81 NF2 gene, 80 NF-kappaB transcription factor, 51, 53 Nijmegen breakage syndrome (NBS), 79, 80, 81, 83 4-Nitroquinoline-N-oxide (4NQO), 75, 76 Non-Hodgkin’s lymphoma, 151, 157, 158, 162, 164, 171, 209, 227, 229, 231 Nuclear Electric, 190 Nuclear facilities. See also Nuclear industry workers; individual facilities accidents, 208, 209, 211, see Chernobyl accidents commercial power plants, 3, 190 dosimetry in population exposures, 209-211, 212, 213, 214, 229-232 fuel processing plants, 190, 199-200, 209, 212, 213, 215, 229, 234 and leukemia, 190, 213 occupational exposures, 190 population exposures in proximity to, 208-215 U.S. population exposure to radiation from, 3, 5 Nuclear Industry Family Study, 233 Nuclear industry workers. See also Occupational radiation exposure; individual facilities and sites age associations, 200 assessment of exposure, 193-194 atomic bomb survivors compared, 201, 203 bone cancer, 201 cancer incidence and mortality estimates, 191, 194-198, 200, 201, 202, 203 cesium-127 exposure, 202 Chernobyl liquidators, 57, 58, 60, 114, 129, 202-204, 226, 227 childhood cancers following parental preconception exposures, 229, 230-232, 233 chromosome aberrations, 57, 58 cohort characteristics, 191-193 commercial nuclear power facilities, 190 confounding factors, 136, 198, 199-200 defined, 190, 191 design of studies, 138-139, 198 dosimetry, 60, 138-139, 190, 191, 192, 193, 198-199, 201, 202, 203, 231, 233, 290 epidemiological studies, 138-139, 189, 190-193, 233 follow-up studies, 190, 192, 193, 202-203 Hanford workers, 135, 190, 191, 192, 195, 196, 198-199

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 healthy worker effect, 194 heavy metal exposures, 200 internally deposited radionuclides, 190, 193, 194, 199-200, 201 leukemia, 14, 190, 191, 196, 197, 198, 199, 200, 201, 202-204 liver cancer, 201 lung cancer, 135, 190, 198, 200, 201 at Mayak plutonium production complex, 13-14, 57, 190, 201-202 modifiers of radiation risk, 200-201 monitoring exposure, 189, 201 multiple myeloma, 197 mutations, 60 plutonium exposure, 190, 194, 199, 200, 201-202 pooled analyses of studies, 14, 191-193, 194-195, 198, 200 prostate cancer, 197-198, 200 protracted exposures, 200-202 reproductive health, 233 risk estimates, 194-198, 203-204, 290 risk modeling, 138, 262, 268, 275, 290 Sellafield Nuclear Facility, 57, 58, 190, 192, 194, 195, 196, 197, 229, 230, 231 sensitivity of studies, 5-6 skin cancer, 190 smokers/smoking, 194, 198, 199 socioeconomic status, 199 solid cancers, 201 thyroid cancer, 203-204 uncertainties in data, 14, 194, 198 Nuclear medicine, U.S. population exposure from, 3, 5 Nuclear membrane damage, 29, 49 Nuclear Regulatory Commission (U.S.), 2 93 Nuclear weapons testing Bikini test site, 234 British tests, 212, 213, 214, 235 Castle BRAVO, 214 dosimetry, 212, 213, 214 and leukemia, 212, 213 multiple myeloma, 214 mutation rates, 114, 128-129 Nevada Test Site, 234 Operation HARDTACK, 213 Operation UPSHOT-KNOTHOLE, 6 participant exposures, 6, 212, 213, 214 population exposures, 3, 5, 6, 114, 212-215, 234, 276 Semipalatinsk test site, 114, 128-129 and thyroid cancer, 212, 215, 234, 276 U.S. tests, 6, 213, 234 Nucleotide pools, alterations in, 48 O Oak Ridge National Laboratory, 190, 191, 192, 193, 194, 195, 196, 198, 200 Oak Ridge X-10 Plant, 191, 192, 195 Oak Ridge Y-12 plant, 190, 191, 192, 195, 200 Observational studies, defined, 133 Occupational radiation exposure. See also Nuclear industry workers; Radiation workers; specific occupations and cohorts adaptive response, 51, 53 airline and aerospace employers, 204 BEIR V report, 190 and cardiovascular disease, 199 confounding in, 136, 189, 194, 198, 199-200, 205 dose limits, 5, 43 dose-response relationship, 189 epidemiological studies, 189-190 healthy worker effect, 189, 194, 205 medical and dental personnel, 189, 204-205, 266; see also Radiologists and radiologicl technicians monitoring, 189 Portsmouth Shipyard Study, 135, 136 and reproductive health, 5, 233 risk estimates, 280 sensitivity of studies, 5-6, 189 skin cancer, 2 types of, 189 uncertainty in, 14 of U.S. population, 3, 5 Ocular albinism, 93 Oncogenes. See also Proto-oncogenes; Tumorigenesis, radiation induced activation, 65 defined, 376 Oncovin, 130 Oocytes chemotherapy effects, 130 primordial, 92 sensitivity to cell killing, 75, 98-99, 119 Oropharyngeal cancers, 148, 149 Osteogenesis imperfecta, 98, 103, 125 Osteopetrosis, 98 Osteosarcoma, 69, 78, 87. See also Bone cancer Otosclerosis, 98 Ovarian carcinoma in atomic bomb survivors, 147, 148, 149, 269 dose-response relationship, 12, 50 genetic susceptibility, 67, 69, 74, 75, 76 incidence, 298 mortality, 298 radiotherapy-related, 80, 84, 160, 164 risk models and estimates, 272, 278, 279, 280, 282, 285, 294, 303-306 Oxford Survey of Childhood Cancer, 10, 172-173 Oxidative stress adaptive response to, 50 DNA damage, 19, 30-32, 34, 40-42, 50 DNA repair, 31-32, 40-42, 48 Oxygen, and radiation resistance, 50 oxyR transcription factor, 50 P p21 protein, 37, 39, 53, 54 p53, 35, 36, 37, 39, 48, 49, 53, 54 Pair-production process, 20-21 Pancreatic cancer, 147, 148, 149, 163, 164, 168, 204 Pantex, 190 Paracrine growth factors, 86 Paracrine proapoptotic or antiapoptotic factors, 54 Parathyroid cancer, 80 Parkinson’s disease, 153 Parotid gland, tumors of, 171 PCNA (proliferating cell nuclear antigen) protein, 32, 33, 39, 53 Peptic ulcer, 163, 174, 175, 185, 242, 287, 288 Peroxyl radicals, 31 Phenylketonuria, 93 Phosphatidyl-3-inosityl enzymes, 36 Phosphorylation of histone protein, 36 of kinases, 37 Photo effect, 22 Photoelectric process, 20 Photons absorption and scattering, 20-21 annihilation events, 21 defined, 376 energy transfer, 19, 20-21 linear dose coefficient, 28 penetration depth, 21 spectral distributions, 20-22 Photosensitivity, 80 Physical aspects of ionizing radiation epidemiological studies, 24-26 experimental observations, 28-29 genetic damage mechanisms, 26-27 in vivo studies, 24 LET, 22-24 neutron interaction with tissue elements, 27-29 photon spectral distributions, 20-22 RBE, 22-29 track structure, 10, 21 types of radiation, 19-20 PI-3 kinase, 67 Pituitary tumors, 74, 152 Plutonium-239, 20, 190, 194, 199, 200, 201 PMS1 and PMS2 genes, 60 Poly-ADP-ribose synthetase, 32, 33, 34 Polycystic kidney disease, 98 Polymerase β (POL β), 32, 33, 34, 35 Polymerase δ (POL δ), 32 Polymerase chain reaction, 127, 130 Polynucleotide kinase (PNK), 32, 33 Polyposis of intestine, 98 Porphyria, 98 Portsmouth Naval Shipyard Study, 135, 136, 191, 192, 197, 200 Postradiation generation progeny first, 116 genetic disease risk, 116 mutations in, 70 second, 116 Potential recoverability correction factor (PRCF), 119 for autosomal dominant diseases, 110, 115, 119 for autosomal recessive diseases, 110-111, 115 BEIR V methods compared, 115 for chronic multifactorial diseases, 111, 115, 119 for congenital abnormalities, 111

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 estimates, 110 multisystem developmental abnormalities, 115 and revision of risk estimates, 109-110 strengths and weaknesses, 111, 119 weighted, 115 for X-linked diseases, 110, 115, 119 pRb, 39 Prednizone, 130 Pregnancy outcomes, adverse, 8, 131 Primary basilar impression, 98 Premature chromosome condensation techniques, 46 Prkdc gene, 71 Procarbazine, 130 Prolactin, 76 Prostate cancer, 147, 148, 149, 164, 200, 204, 269, 272, 278, 279, 280, 282, 298, 303-306 Prostate hyperplasia, 153 Protein kinases, 35-39, 51, 55 Protein-8 (XIP8), 56 Protracted exposure and bone cancer, 75 and breast cancer, 176, 180, 243 and cancer risk assessment, 241, 243 and DNA damage, 31 dose-rate effects distinguished from, 77 genetic risk assessment, 92 and life span, 76, 77 occupational, 189, 200-202 radiation protection implications, 189 reduction in risk for, 246 thyroid cancer, 182 and tumorigenesis, 75 Protons dose-effect relationships, 28 energy transfer, 19, 20 recoil, 27, 28 Proto-oncogenes, 66, 68, 80, 81-82 PTC gene, 80 Ptch gene, 66, 68, 69, 82, 83 5′,8-Purine cyclodeoxynucleosides, 34 Pyloric stenosis, 120 Pyrimidopurinone, 34 Q Quality factor (Q) basis for, 22 defined, 376 Quantitative studies in experimental tumorigenesis, 73-79 R RAD50, 37 Rad51, 38, 53, 82, 83 RAD52, 38 RAD54, 38 Radiation Effects Research Foundation, 91, 140, 141, 142, 152, 267, 269, 270, 271, 285, 286, 296, 297, 298, 301, 302, 307. See also Atomic bomb survivors; Life Span Study Radiation protection control measures, 193, 276 dose units, xi genetic susceptibility implications for, 85 photon energy considerations, 24 protracted exposures and, 189 quality factor, 22 RBE and, 276 Radiation quality. See also Quality factor LET as a measure of, 22-24 and mutation frequency, 47 weighting factor, xi, 24 Radiation resistance, 30, 32, 40-42 as adaptive response, 37, 51 DNA repair, 49 priming dose and, 51 Radiation weighting factor, xi, 24 Radiation workers. See Nuclear industry workers; Occupational radiation exposure Radical scavengers, 29, 30 Radioisotopes. See also specific radioisotopes diagnostic exposures, 156 natural in human body, 30, 43 Radiologists and radiologic technicians breast cancer, 205 colon cancer, 205 leukemia, 189, 204, 205 lung cancer, 204, 205 lymphoma, 204, 205 mortality rate, 2, 189, 204, 205 multiple myeloma, 204, 205 pancreatic cancer, 204 prostate cancer, 204 skin cancer, 2, 204, 205 Radionuclides. See also Internally deposited radionuclides; specific radionuclides in utero exposures, 330 organically bound, 330 in work environment, 199-200 Radiosensitivity age and, 68 animal studies, 34, 69, 71, 82-83 of bone marrow, 173 of breast tissue, 56, 86, 173 cardiovascular system, 185-186 cell cycle phase and, 45, 49-50, 55, 82, 83, 86, 113 and cell killing/lethality, 55-57 chromosomal, 82, 86 DNA repair defects and, 32, 34, 37, 40, 56, 69, 71, 80, 82, 83, 87, 239 dose fractionation, 55 gene polymorphisms, 87 heritable, 82-85, 87 human data, 82, 83-85 hypersensitivity to low doses, 11, 32, 45, 47, 51, 55-57, 71, 82, 239 mutational, 47, 98-99 of oocytes, 75, 98-99, 119 sex differences, 119 thyroid gland, 173, 234 and tumorigenesis, 82-85, 87 Radiotherapy studies ankylosing spondylitis cohort, 164-165, 174, 176, 177, 185 benign breast disease cohorts, 163, 174, 177, 180, 185 for benign diseases in adults, 155, 162-166 benign diseases in children, 155, 166-167, 181 benign gynecological diseases, 163-164 bladder cancer in recipients, 157, 158, 162, 163, 164 bone cancer in recipients, 157, 161, 162, 164, 167 brachytherapy recipients, 162 breast cancer patients, 26, 84, 86, 135, 157, 159-160, 164-165, 167, 168, 169, 174, 175, 176-180, 186-187, 205, 243 cardiovascular disease mortality, 159, 160, 185-187 cell killing, 155 cervical cancer survivors, 26, 135, 157-158, 174, 176, 177, 185 children, 9, 84, 156, 161-162, 166-170 chromosomal aberrations, 53 dose-response relationship for secondary cancer, 157-170 dosimetry, 155, 156-157, 159, 161, 176-177, 183, 184, 186, 187 extrapolation to other populations, 155 genetic effects, 9 Hodgkin’s disease patients, 130, 158-159, 174, 176, 177, 242-243 for hormonal infertility, 164 hyperthyroidism studies, 165-166, 169, 181, 185, 234 for malignant diseases, 9, 130, 155, 156, 157-162 and minisatellite mutations, 114, 130 mouse studies, 130 non-Hodgkin’s lymphoma patients, 162 occupational exposures, 205 ovarian cancer patients, 160 in peptic ulcer patients, 163, 174, 175, 185 postpartum mastitis cohorts, 26, 163, 177, 180 and radiosensitivity, 82, 83-87, 155 registries, 155 secondary tumors, 84-85, 86, 88, 135, 155, 157-162, 173-187 site-specific cancer risk estimates, 173-187 and skin cancer, 68 skin hemangioma cohorts, 168-169, 174, 175, 176, 177, 180, 181, 183, 185 testicular cancer patients, 160-161 thymus gland enlargement, 156, 167-168, 176, 177, 180, 181, 182 thyroid cancer patients, 161 thyroid diseases (benign), 165-166, 169 tinea capitis cohort, 68, 155, 156, 166-167, 181, 182, 183 tonsil enlargement cohort, 155, 169, 181 uterine cancer patients, 162 Radium-224, 2, 269 Radium-226, 163, 164, 168, 169, 183, 185, 209 Radon, 30, 262. See also Uranium miners and lung cancer, 242 sources, 3, 43, 68 Randomized intervention trials, 133-134 Rare diseases (early onset), 98

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 RAS gene, 68 Rats Eker strain, 82, 83 mammary cancer, 28, 74, 76 renal carcinoma in Tsc-2-deficient genotype, 69 skin cancer, 75, 76 Sprague-Dawley strain, 28, 74 tumor-suppressor-gene-deficient, 82, 83 RB1 and RB2 genes, 80, 125 Reactive oxygen species, 31-32, 40-42, 48 adaptive response to, 50 bystander effect, 54 Rectal cancer in atomic bomb survivors, 147, 148, 149, 151 radiotherapy-related risks, 157, 158 Relative biological effectiveness (RBE) alpha particles, 71 animal studies, 28-29 and cancer risk assessment, 276 cell cycle phase and, 50 and chromosome aberrations, 24, 27-28, 276 defined, 376 dose-rate effects on, 21, 24, 28 experimental observations, 28-29 gamma rays, 21, 22-24, 126, 276 and gene mutations, 47 and genomic instability, 71 LET of radiations and, 21, 24, 31, 47 neutrons, 20, 27-29, 126, 143, 146, 297 protracted exposure and, 75, 176, 180, 243 uncertainty in, 29, 286 X-rays, 22-24, 276, 286 Relative risk, defined, 132, 376 Renal carcinoma, 69, 70, 80, 222 Research recommendations adaptive response, 53, 314 atomic bomb survivor studies, 18, 317-319 baseline frequencies of Mendelian diseases, 316-317 biological phenomena at low doses, 9, 16-17, 314-315 bystander effects, 314 Chernobyl cleanup workers, 204 doubling dose calculations, 316 environmental radiation studies, 17-18, 321 epidemiological studies, 18, 317-321 genetic effects of radiation, 17, 316-317 genetic susceptibility to cancer, 17, 315 genomic instability, 49, 53, 315 hormesis, 17, 315 hyperradiosensitivity for low doses, 314 integration of biology and epidemiology, 321-322 lifetime risk models, 322-323 medical radiation studies, 5, 17, 319-320 molecular and cellular responses to ionizing radiation, 15-16, 313-314 multisystem developmental abnormalities, 317 occupational radiation studies, 17, 320-321 potential recoverability correction factor, 317 radiation-sensitive subpopulations, 314 tumorigenic mechanisms, 17, 315-316 whole-body CT scan cohorts, 5 Respiratory system cancer. See also Lung cancer atomic bomb survivors, 149, 292 Chernobyl accident and, 218 model, 292 Restricted LET defined, 19 n.1 dose averages, 22, 23, 24 Retinal tumors, 80 Retinoblastoma, 80, 84, 98, 103, 125, 161 ret/PTC genes, 68, 81-82, 246 Rhesus monkeys, oocyte radiosensitivity, 99 Risk assessment. See also Cancer risk assessment; Genetic risk assessment; Models/modeling absolute risk, 260-261 BEIR I approach, 138 Committee approach, 6-9 confidence intervals, 133, 136, 137-139, 176 defined, 377 definition of risk, 260 direct estimates, 261, 290 excess risks, 132, 137-138, 260-261 incidence rates and, 259, 260-261 incomplete covariate information and, 265 lifetime risk projections, 137, 240, 264-265 mathematical models, 261-262 measures of risk, 132 methodology, 137-138, 259-261 pooling data from multiple studies, 169, 172 probability models, 260, 265 RBE in, 28 relative risk, 261 risk models, 138-139, 261-266 sample sizes, 297 validity of estimates, 266 Rochester Thymus Study, 26, 180, 181, 292 Rocketdyne/Atomics International, 191, 192, 194, 197, 200 Rocky Flats, 190, 191, 192, 193, 195, 196, 197, 199 Roentgen, Wilhelm Conrad, 1-2, 156 RPA, 38 Russell, William, 100 n.1 Ruthenium-106, 212, 213, 214 S Saccharomyces cerevisiae, DNA repair in, 30, 36, 40-42 Sahlgrenska University Hospital, 168 Salivary gland tumors, 149-150, 161, 165, 167, 269 Sarcomas, 67, 69. See also Osteosarcoma; Soft tissue sarcoma Sasakawa Foundation, 225 Savannah River Site, 190, 192 Scaffold proteins, 32, 33, 34 Schwannomas, 152 Scoliosis, 155, 172, 176, 177, 187 Searle, Tony, 100 n.1 SEER (Surveillance, Epidemiology, and End Results) registry, 242 Segmental aneusomy syndromes, 112 Sellafield Nuclear Facility workers, 57, 58, 190, 191, 192, 195, 196, 197, 198, 199, 200, 229, 230, 231, 233 Seminoma, 130 Semipalatinsk nuclear test site, human minisatellite loci mutations, 114, 128-129 Signal transduction pathways adaptive response, 51, 53 bystander effects, 53-54, 251 DNA repair, 32, 34, 36-39, 48, 49, 54, 80 and dose-response relationships, 62 and genomic instability, 78 hypersensitivity to radiation and, 56 Sister-chromatid exchanges, 36, 53, 54 fusion, 48, 71 replication, 49, 245 Skeletal disorders, 80, 112, 115, 116. See also Bone cancer Skin cancer age dependency, 298 animal studies, 74, 75, 76, 87 in atomic bomb survivors, 148, 149, 150-151, 269, 295 beta particles and, 75 caretaker gene, 67 children, 161, 167 dose-response relationship, 74, 76, 151, 245 excess relative risk, 148 fluoroscopy and, 2 gatekeeper gene, 66 genetic susceptibility to, 80, 84, 87 latent damage, 76, 167 in mice, 69, 76 in radiologists, 2 radiotherapy-related risks, 84, 162, 167 risk estimates, 245, 270-271, 282, 294, 295 in tinea capitis radiotherapy patients, 68, 167 UV-induced, 75, 151 xeroderma pigmentosum and, 79 Skin hemangioma cohort, 26, 168-169, 172, 174, 175, 176, 177, 178, 180, 181, 183, 185, 287 Smoke detectors, 3 Smokers/smoking and carcinogenesis, 242 confounding in radiation studies, 57, 138, 150, 198, 199, 242, 245 and liver cancer, 242 and lung cancer, 87, 135, 138, 150, 174, 176, 198, 242, 245 radiation exposure in tobacco, 3, 4 synergistic effects, 242 Socioeconomic status, confounding in radiation studies, 199 Soft tissue sarcoma, 80, 84, 161 Solid cancers, 6 age dependencies, 297-298 in atomic bomb survivors, 142, 143, 144-147, 245, 297-307 baseline risks, 241 Chernobyl accident and, 227-228 defined, 377 dose-response relationship, 74-75, 142, 144, 145-146, 201, 245, 298 incidence, 144, 279, 298-307

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 medical-use-related risks, 161, 172, 287-289 mortality data, 144, 280, 298-307 murine studies, 74-75 risk assessment models, 143, 144-145, 241, 269-271, 279, 284, 287-289, 297-307 sex differences, 145, 298 spontaneously occurring, 65, 66-67 sum-of-sites estimates, 279-280, 296 vasculature, 66 Somatic cells defined, 377 DNA repair in, 36 mutagenesis in, 46-47, 66, 113, 127 tumorigenesis, 66 soxR gene, 36, 37 soxRS transcription factor, 50 Specific locus tests dominant mutations in mice, 100-101 Spherocytosis, 98 Spondylosis, 165 Spontaneous mutations, 91 clusters, 97 dominant disorders, 97-98 doubling dose calculations, 8, 96-101, 119 estimation of rates, 97-98 extrapolation from mice to humans, 96-97 frequencies, 47, 94, 102 in genetic risk assessment, 96, 102, 109-111, 124-125 germinal mosaics, 97 in human genes, 96-98, 109-111, 124-125 mechanisms, 124-125 in mice, 96-97, 126 and natural selection, 94, 102 paternal age effects, 97 point, 47 radiation-induced damage compared, 30, 124-125 recoverability in live births, 109-111, 124, 125 sex differences, 96-97 Springfields nuclear workers, 191, 192, 195, 196 Squamous cell carcinoma, 67, 80, 151 Stanford University Medical Center, 159 State Chernobyl Registries, 203 Statistical methods atomic bomb survivors, 143-144 inference tools, 137-138 Statistical power of studies, 136 Stem cell spermatogonia, 92, 98, 113, 119, 126, 127 Steroid hormone receptor genes, 86 Steroid sulfatase deficiency, 93 Stomach cancer. See also Digestive system cancer in atomic bomb survivors, 147, 148, 149, 150, 151, 215, 240, 242, 269, 288 baseline lifetime risk estimates, 278 in cervical cancer survivors, 158, 185, 288 childhood exposures and, 168, 185 etiology, 241-242 excess relative risk, 12, 287, 288, 289, 301-302 incidence, 173-174, 185, 278, 284, 298, 303, 305, 304, 306 mortality, 278, 282, 298 radiotherapy-related, 12, 157, 159, 160, 163, 164, 166, 168, 185, 186, 287, 288, 289 risk factors, 241-242, 302 risk models and estimates, 12, 173, 185, 186, 215, 269, 272, 275, 278, 279, 280, 282, 284, 285, 294, 301, 303-306 risk transport model, 241-242 Strontium-90, 212, 213, 214, 269, 276 Superoxide radical, 30, 50 Swedish benign breast disease study, 26 Swedish Cancer Registry, 166 Swedish Family Cancer Database, 88 Swedish infant skin hemangioma patients, 26 Synchrotron radiation, 24 T Tcr gene, 68 TEC facility, 200 Televisions, 3 Telomere-like repeat sequence arrays, 69 Telomeres, 34, 48, 71-73 Terrestrial radiation, 43 Testicular cancer, 160-161 12-O-Tetradecanolyphorbol-13-acetate (TPA), 75 Tetrapeptide repeats (TPRs), 52 Therapeutic irradiation. See Medical uses of radiation; Radiotherapystudies Thorium, 3 Thorotrast, 68, 150 Three Mile Island, 208, 209, 211 Three-Country Study, 14 Thymine glycols, 52 Thymus gland enlargement, radiotherapy risks, 26, 167-168, 176, 177, 180, 181, 182, 243, 273, 287, 292 Thyroid cancer age and, 167-168, 180-181 age at exposure and, 74, 76, 86, 149, 167, 181-182 in atomic bomb survivors, 148, 149, 181, 244, 269, 295 BEIR V model, 291-292, 294 benign thyroid nodules, 168, 244 in cervical cancer survivors, 181 Chernobyl accident and, 68, 72, 203-204, 215-226, 234-235, 246, 276 childhood exposure and, 68, 72, 149, 161, 162, 166, 167, 168, 169, 181, 182, 214, 215-226, 234, 244, 246, 287 chromosomal aberrations and, 67, 246 coherence of BEIR VII model with other studies, 287 diagnostic irradiation and, 171, 234 dose-response relationships, 149, 160, 162, 167, 168, 169, 182, 215, 224, 225, 276 ethnic origin and, 167 etiology, 244 excess relative risk, 12 familial medullary, 80 genetic susceptibility, 80, 81-82, 86, 244, 246 hormones and, 244 in utero exposure and, 224, 225 incidence, 180-181, 244 iodine deficiency and, 225, 244 iodine-131 exposure and, 12, 68, 161, 165, 171, 182, 213, 215-226, 233-235, 276 latent phase, 215 medical-exposure-related risks, 12, 161, 180-182, 234, 287 medullary, 86, 244 model, 273 mortality, 165, 181 multiplicative model, 244 nuclear facility proximity and, 213, 215, 234, 276 nuclear weapons tests and, 212, 234, 276 papillary, 68 pooled analyses or risks, 181, 268, 287, 295 radiosensitivity of thyroid gland, 173 radiotherapy-related risks, 157, 159, 161, 162, 166, 167, 168, 169, 181-182, 234 relative risk, 244 risk assessment, 181, 244, 268, 270-271, 272, 273, 275, 282, 286, 287 risk estimates, 173, 180-182, 282, 294 risk factors, 244 sex differences, 161, 167, 181, 244 Thyroid diseases benign tumors, 225, 244 dose-response relationship, 153 radiotherapy-related risks, 165-166, 169 Thyroid stimulating hormone, 244 Thyrotoxicosis, 166 Tinea capitis cohorts pooled data for risk assessment, 273 radiotherapy-related risks, 68, 155, 156, 166-167, 181, 182, 183 skin cancer, 68 thyroid cancer, 181, 182 Tobacco, 3. See also Smokers/smoking Tonsil enlargement, 169 Topoisomerase, 34 TP53 gene, 67-68, 79, 80, 81, 82, 83 Tradescantia, 24 Traits, heritability of, 106 Transcription factors, 51, 53, 66, 67 Transforming growth factor-α (TGF-α), 55 Translocations cell cycle phase and, 45 dose-response relationships, 57, 58, 60, 61 in mice, 57, 58 nonreciprocal, 48 segmental jumping, 72 telomeric sequences at, 72 Trichothiodystrophy, 80 Triliated thymidine (3HTdR), 53, 55 Tritium, 200 Trp53 gene, 69, 70 TSC1 gene, 80 Tsc-2 gene, 69, 80 Tuberculosis patients. See Fluoroscopy Tuberous sclerosis, 80, 82, 83, 98 Tumor progression, 49 Tumor promotion, 240, 241 action of, 241 and dose-response relationships, 75, 76 environmental/lifestyle factors, 242, 244, 254 genes, 66, 68, 80, 81-82 hormonal factors, 243, 244 stomach cancer, 241-242

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 Tumor registries, 141, 142, 147-148, 150, 151, 152 Tumor suppressor disorders, 80, 84 genes, 39, 65, 66, 67-68, 69, 80, 80, 81, 82-83 Tumorigenesis, radiation induced adaptive responses, 12, 51, 52, 62, 78-79, 250-251 aggressive, 72 alpha particles and, 70 animals studies, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240 cell killing and, 12, 74, 75, 76, 82 chromatid instability and, 70-73 chromosome aberrations and, 24, 46, 66, 68-69, 70, 72-73, 74, 82, 86 confounding stress factors, 71 DDREF, 77-79, 246-250 diet and, 242 DNA damage response and, 6, 11, 65, 68, 69, 70, 73, 82, 83, 239, 227-228, 239, 246 dose-response relationships, 12, 45, 50, 55, 59, 60, 61-62, 68, 70, 73-77, 84, 89, 140, 245-246 epidemiologic studies, 68 etiology at different histologic sites, 241-245 fractionation kinetics, 73, 75-76, 78-79, 182 genetic susceptibility, 12, 65-66, 79-90 genomic instability and, 11-12, 39, 49, 65, 66, 67, 69, 70-73 in hematopoietic cells, 70-71 human data, 68, 71, 83-85 latency, 65, 68, 78 life-span shortening, 76-77 lymphoma and leukemia, 68-70, 71, 73-74 malignant transformation, 51-52, 62, 78-79 mammary epithelial cells, 71-73 mechanisms, 11-12, 27, 65, 66-70, 74, 75, 76, 81-82, 89, 245 monoclonal origins, 11, 245, 253-254 mouse models, 68-69, 70, 71 mutations and, 11, 65, 66-70 persistence of initiated cells postirradiation, 76 phases and process, 11, 66, 240 in progeny, 70 quantitative studies, 73-79, 89 RBE for, 24, 28, 29 solid tumors, 74-75 spontaneous mechanisms compared, 11, 12, 66-67, 70, 239 target for, 54 telomere sequence instability and, 12, 71-73 temporal projections of risk, 239-240 UV radiation and, 67-68 Twin studies of genetic susceptibility to cancer, 88 of multifactorial diseases, 93 U Ulcer patients dose-response relationship, 153 radiotherapy-related cancer risk, 163 Ultraviolet light DNA damage, 40 skin cancer, 75, 151 tumorigenesis, 67-68, 75 Uncertainties. See also Bias; Confounding factors from age-related effects, 297 in atomic bomb survivor data, 130, 131, 141, 147, 172, 285-286 cancer risk estimates, 25-26, 147, 174, 251, 268, 272-273, 275, 276, 278, 279, 280, 284-286, 297, 308-310 in Chernobyl data, 128, 129, 202-203 chromosomal radiosensitivity, 82 combining sources of, 309-310 in cross-population transport, 279, 284, 285, 286, 296 in DDREF, 279, 284, 285, 286, 295, 296, 310 defined, 377 in diagnostic radiation risk estimates, 286 in dose-response relationships, 246 in dosimetry, 3, 14, 128, 129, 139, 142, 169, 198-200, 233, 241, 266, 285 in doubling dose estimates, 98-99, 130, 131 EPA assessment of, 284 in epidemiological studies, 133, 284 in error correction, 296 in exposure estimates, 114, 174 in genetic risk estimates, 98-99, 114 joint analysis, 295 LAR analysis, 278, 279, 284, 308-310 in lifetime cancer risk, 278, 279, 284-286 Monte Carlo analysis, 293, 295 NCRP assessment of, 284 NIH assessment of, 284, 295 occupational exposures, 14, 194, 198 in population effects, 286 procedures for addressing, 308-310 quantitative evaluation, 278, 284-285 in radiation exposure data, 3, 169 in RBE, 29, 286 in risk estimates, 29, 284, 286 from sampling variability, 278, 279, 280, 284, 285, 296, 308-309 sources, 133, 285, 295-296 statistical, 29 time since exposure, 275 Underground miners. See Uranium miners United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), 91, 93 cancer risk model, 138, 240, 268, 272, 274, 275, 277-278, 282-283, 293-294, 297-298, 307 congenital abnormality frequencies, 112 DDREF, 131, 246, 249 defined, 377 genetic risk calculations, 92, 94, 95, 96, 109, 111, 112, 118, 131 lifetime cancer risk estimates, 294 mutation rate estimation, 109, 111 occupational exposure studies, 190 United Nuclear Corporation, 190 Units of dose, xi, 2 Uracil, 30 Uranium, 2, 3, 20, 269 Uranium miners, 190 lung cancer, 68, 138, 242 risk modeling, 262 Urinary tract cancer. See also Bladder cancer ankylosing spondylitis cohort, 164 atomic bomb survivors, 148, 149 cervical cancer survivors, 157, 158 Chernobyl accident and, 223, 227-228 U.S. Department of Energy, nuclear facilities, 190, 198 U.S. Environmental Protection Agency (EPA), 274, 275, 282, 283, 293, 294 U.S. Food and Drug Administration, 5 U.S. Scoliosis Cohort Study, 172 Uterine bleeding disorders (benign), 163-164, 183, 287, 288 Uterine cancer in atomic bomb survivors, 147, 148, 149, 269, 298, 303-306 radiotherapy-related, 157, 158, 159, 162, 163, 287 risk models and estimates, 272, 278, 279, 280, 282, 303-306 Uterine fibroma, 86 Uterine myoma, 151-152, 153 V Vaginal cancer, 157 Varicose veins, 95 VHL gene, 66, 80, 81 Vinblastine, 130 Vincristine, 130 Von Hippel-Lindau syndrome, 80, 125 W Warthin’s tumor, 150 Water, electron ionization, 21, 29-32 World Health Organization, 128 WT-1 gene, 66, 80 X Xenon, 209 Xeroderma pigmentosum, 79, 80, 81 X-linked disorders, 79 XP-A to XP-G gene, 67, 68, 80 XPV gene, 80 X-rays. See also Radiotherapy studies animal studies, 68, 69, 100-101 atomic bomb explosion, 22 bystander effects, 54 cancer risk estimates, 171, 276 childhood exposures, 211 chromosome aberrations, 48, 86 correction to gamma rays, 24 defined, 378 diagnostic, 3, 4, 5, 6, 21, 22, 156, 171; see also Mammography discovery and early studies, 2 DNA damage, 30, 32, 33, 36 dose-response relationships, 49, 56, 61, 62

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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2 electron tracks, 62 luggage inspection scanners, 3 mutations, 68, 91, 99, 100-101 from photoelectric process, 20, 22 photon energies, 20-22, 23 physical aspects, 19-29 priming dose, 55, 78 RBE, 22-26, 276, 286 resistance to, 30, 32, 40, 42 soft, 20, 22, 55, 286 spikes, 20 tumorigenesis, 24-26, 49, 68, 69, 75 ultrasoft, 22 U.S. population exposure, 3, 5 XRCC1 protein, 32, 33, 34 XRCC2 protein, 35, 36 XRCC3 protein, 35, 36 XRCC4 protein, 35 Z Zinc-65, 200 Zirconium-95, 212, 213, 214

Representative terms from entire chapter:

chernobyl accident