Abstract
Recently, we irradiated mice heterozygous at the Dlb-1 locus (Dlb-1b/Dlb-1a) with low dose-rate gamma-rays for 483 days and obtained experimental evidence for the accumulation of induced mutations in small intestinal stem cells. To determine whether the same is true after high dose-rate irradiation, heterozygous mice were irradiated repeatedly at an interval of two or three weeks with an X-ray dose of 40 cGy at a dose rate of 50 cGy/min, starting at an age of 10 weeks and ending at an age of 58 weeks. Small intestines were sampled from control and irradiated mice 2 weeks after doses of 0.4, 2, 4, 6 and 8 Gy and subjected to the Dlb-1 mutation assay in which evidence of mutations of Dlb-1b gene in the stem cells was detected as mutant clones on the surface of villi. Frequency of mutant clones (F), i.e., the number of clones detected per 10000 villi, in the irradiated series increased approximately linearly as the number of treatments increased without significant dose- and age-dependent change in the size of mutant clones. F value in the control series also increased in a linear fashion. From dose-response data corrected for control F values, we estimated induced rate of mutant clones (10-4 villi·Gy-1) to be 4.35±0.33, which is greater by a factor of 4.8 than rate after long-term chronic gamma-irradiation. We thus may conclude that mutations induced by high dose-rate irradiation accumulate in somatic stem cells, as it was the case after chronic irradiation and that mutagenic effectiveness of long-term irradiation depends on the dose and dose-rate of radiation.
