Possible stimulatory effects have been reported for radiation exposure, such as mobilization of intracellular calcium (Liu 1994), gene activation (Boothman and others 1993), activation of signal transduction pathways (Liu 1994; Ishii and others 1997), increase in antioxidants such as reduced glutathione (GSH; Kojima and others 1997), increase in lipoperoxide levels (Petcu and others 1997), and increase in circulating lymphocytes (Luckey 1991). The general thesis presented is that stress responses activated by low doses of radiation, particularly those that would increase immunological responses, are more beneficial than any deleterious effects that might result from the low doses of ionizing radiation. Although evidence for stimulatory effects from low doses has been presented, little if any evidence is offered concerning the ultimate deleterious effects that may occur. In the section of this report on observed dose-response relationships at low doses, bystander effects and hyper radiation sensitivity for low-dose deleterious effects in mammalian cells have been observed for doses in the 10–100 mGy range. End points for these deleterious effects include mutations, chromosomal aberrations, oncogenic transformation, genomic instability, and cell lethality. These deleterious effects have been observed for cells irradiated in vivo as well as in vitro.
The radiation-adaptive response in mammalian cells was demonstrated initially in human lymphocyte experiments (Olivieri and others 1984) and has been associated in recent years with the older concept of radiation hormesis. A more extensive treatment of adaptive effects is discussed in another section of this report. Radiation adaptation, as it was initially observed in human lymphocytes, is a transient phenomenon that occurs in some (but not all) individuals when a conditioning radiation dose lowers the biological effect of a subsequent (usually higher) radiation exposure. In lymphocyte experiments, this reduction occurs under defined temporal conditions and at specific radiation dose levels and dose rates (Shadley and others 1987; Shadley and Wiencke 1989). However, priming doses less than 5 mGy or greater than ~200 mGy generally result in very little if any adaptation, and adaptation has not been reported for challenge doses of less than about 1000 mGy. Furthermore, the induction and magnitude of the adaptive response in human lymphocytes is highly variable (Bose and Olivieri 1989; Hain and others 1992; Vijayalaxmi and others 1995), with a great deal of heterogeneity demonstrated between different individuals (Upton 2000). Also, the adaptive response could not be induced when the lymphocytes were given the priming dose during G0. Although inhibitor and electrophoretic studies suggest that alterations in transcribing messenger RNA and synthesis of proteins are involved in the adaptive response in lymphocytes, no specific signal transduction or repair pathways have been identified. A recent study (Barquinero and others 1995), which reported that chronic average occupational exposure of about 2.5 mSv per year over 7 to 21 years induced an adaptive response for radiation-induced chromosomal aberrations in human lymphocytes, also reported that the spontaneous level of aberrations was elevated significantly, presumably by the occupational exposure. (See Barquinero and others  for references to six other reports that basal levels of chromosome abnormalities are in general higher in exposed human populations.) These results suggest that occupational exposure may have induced chromosomal damage in the worker population while protecting lymphocytes from a subsequent experimental radiation exposure administered years after initiation of the chronic exposure. It is unclear whether such competing events would result in a net gain, net loss, or no change in health status.
In general, to observe hormetic effects the spontaneous levels of these effects have to be rather high. The committee notes in the Biology section that a very low radiation dose was reported to cause a reduction in transformation in vitro below a relatively high spontaneous transformation frequency. However, problems and possible artifacts of the assay system employed are also discussed. When radioresistance is observed after doses that cause some cell lethality—for example, after chronic doses that continually eliminate cells from the population—the radioresistance that emerges may be caused either (1) by some inductive phenomenon or (2) by selecting for cells that are intrinsically radioresistant. Either process 1 or process 2 could occur as the radiosensitive cells are selectively killed and thus eliminated from the population as the chronic irradiation is delivered. In the end, an adaptive or hormetic response in the population may appear to have occurred, but this would be at the expense of eliminating the sensitive or weak components in the population.
In chronic low-dose experiments with dogs (75 mGy/d for the duration of life), vital hematopoietic progenitors showed increased radioresistance along with renewed proliferative capacity (Seed and Kaspar 1992). Under the same conditions, a subset of animals showed an increased repair capacity as judged by the unscheduled DNA synthesis assay (Seed and Meyers 1993). Although one might interpret these observations as an adaptive effect at the cellular level, the exposed animal population experienced a high incidence of myeloid leukemia and related myeloproliferative disorders. The authors concluded that “the acquisition of radioresistance and associated repair functions under the strong selective and mutagenic pressure of chronic radiation is tied temporally and causally to leukemogenic transformation by the radiation exposure” (Seed and Kaspar 1992).