Radiation Dose Reconstruction for Epidemiologic Uses (1995) / Chapter Skim
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6 Biologic Dosimetry and Biologic Markers
6 Biologic Dosimetry and Biologic Markers
Pages 51-61
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From page 51... ...
In order to produce a biologic marker, a harmful agent must interact with cellular macromolecules, including DNA, to induce some chromosome- or DNA-damaging event, such as an aberration, the formation of a micronucleus, a DNA adduct, or a somatic mutation. Biologic markers such as aberrations, micronuclei, DNA adducts, or mutations can be measured in a surrogate tissue or in the specific tissue of interest, that is, the target tissue for the effect.
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From page 52... ...
Because relevant calibration curves for aberrations can be obtained using human lymphocytes in vitro, it is possible to use the frequency of aberrations measured in lymphocytes of the exposed individual to estimate radiation dose when actual physical measures of dose to an individual are unavailable. Results of studies of people accidentally exposed to high radiation doses indicate that doses estimated from yields of aberrations coincide well with the measured doses (Gooch and others 1964, Bender and Gooch 1967~.
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From page 53... ...
can be used to further define stable chromosome aberrations (Pinker and others 1988~. It is a promising cytogenetic method for determining the dose of radiation to an individual, and consequently, to a population, particularly for those receiving protracted exposures or for those exposed a long time ago (Straume and Lucas 1995~.
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From page 54... ...
The rapid nature of the test, the possibility of automation, and the response to multiple environmental insults do make this useful for identifying markers of exposure for some experimental questions and exposure conditions. Genetic or Molecular Markers One method of detecting exposure uses fluorescent-labeled monoclonal antibodies to detect mutations or losses of the alleles on chromosome 4 that code for glycophorin A, a glycoprotein responsible for the M and N blood types found on nonnucleated erythrocytes (Langlois and others 1993; Grant and Bigbee 1993~.
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From page 55... ...
The observation that the grouped data from the survivors of the atomic bombing of Hiroshima and Nagasaki showed a dose-related increase in M0 and N0 variants many years after the exposure indicates that the phenomenon has an extremely long half-life. A positive correlation has been found between increases in M0 variant cells and chromosome aberrations in the survivors many Years after the exposure (Kyoizum~ anct others Amp.
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From page 56... ...
The method used automated techniques to pick up rare red blood cells that contain mutant hemoglobin. Mitigating against the use of betaglobin as a marker of dose for radiation is the fact that the method of assay is extremely cumbersome and expensive, that the mutations observed are very rare, and that the mutations consist of only a single base change they are true point mutations, which are rarely induced by ionizing radiation.
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From page 57... ...
As the cells divide, form hyperplastic nodules, progress to benign neoplasms, and finally form radiation-induced malignancies, the cells lose unstable aberrations but might retain stable chromosome aberrations or other genetic lesions that survive cell division and can be classified as markers of disease or effect. It is essential to conduct studies that will relate markers of dose to markers of effect and explain how both relate to the induction of a specific disease or to the incidence of cancer.
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From page 58... ...
MARKERS OF SUSCEPTIBILITY Heterogeneity with respect to responses to insults like radiation raises concern over potentially susceptible subsets of human populations. Susceptible subpopulations would contain individuals that have different levels of protection from or sensitivity to the genotoxic effects of ionizing radiation.
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From page 59... ...
Later comparison of biologic marker status in individuals who do or do not develop disease could be compared in a nested case-control study that could shed light on the relationship of the marker to the subsequent development of disease and whether the worker might be used in broader studies as a true surrogate for the disease. Therefore, the committee suggests careful consideration be given to creating a cryopreserved repository of tissue, blood, or both, from persons at high risk for cancer after a known exposure to radiation (or other agent)
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From page 60... ...
SUMMARY AND RECOMMENDATIONS The use of biologic markers for dose reconstruction or epidemiologic studies associated with dose reconstruction involves extensive effort and expense, and many of the techniques for finding markers carry much uncertainty (Albertini and others 1990; Grant and Bigbee 1993; Grant and Jensen 1993~. Background variability is a major problem with markers other than dicentrics measured by cytogenetic methods.
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From page 61... ...
26. New assays should be developed to address the problems with individual variability in background, with identification of differences in individual susceptibility to radiation genotoxicity, and with the lack of sensitivity for quantifying low radiation exposures so that acute doses greater than 0.1 Gy (10 red)
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