Accumulation and persistence of mutations induced in somatic stem cells of mice during irradiation with low dose-rate gamma rays for 483 days.

To determine whether mutations continually induced by low-level radiation persist and accumulate in somatic stem cells, mice heterozygous at the Dlb-1 locus (Dlb-1 ^b^/Dlb-1^a^) were irradiated at a dose rate of 0.01 mGy/min or lower for 483 days from 8 to 78 weeks of age to attain a total dose of 0.02, 0.42 or 8.0 Gy. Small intestines were sampled from control and irradiated mice 2 weeks after the completion of irradiation and subjected to the Dlb-1 mutation assay in which evidence of mutations at the Dlb-1 locus in small intestinal stem cells was defected as mutant clones on the surface of villi, and the frequency (F) and the size (S) of mutant clones were measured. More than 10000 villi were observed for each of mice. F was defined as the number of clones detected per 10000 villi observed. S was determined as area occupied by mutant clone relative to whole villus surface.F values with SD in the low, the middle and the high dose groups were 20.0+/-5.4(N-18), 22.4+/-5.0(16), 29.4+/-10.9(17), respectively, the last of which was significantly higher than control frequency of 21.2+/-4.2(19). Thus, frequency of induced mutant clones (f) in the 8Gy irradiated group was 8.3+/-2.2. As compared at the same dose level, this value is equal within experimental errors to a f of 7.3+/-2.5 that had been obtained for young mice at 8 to 9 weeks of age after chronic gamma-irradiation at a dose rate of 1mGy/min; but, it is considerably lower than a f of 50.4+/-10.1 recorded for young mice after acute gamma-irradiation at 1 Gy/min. The mean S values of induced mutant clones (i.e. values corrected for the size of spontaneously arisen clones) did not show significant variation that could be ascribed to the age of mice irradiated and the dose-rate of gamma rays used. We thus may conclude that (1) mutations continually induced by low-level radiation accumulate in somatic stem cells and persist for prolonged time: (2) susceptibility of stem cells to radiation mutagenesis does not change with age.13th International Congress of radiation Researc