Accumulation of cells at G2/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by 252Cf fission neutrons

A previous study on mutagenesis by 252Cf radiation in mouse L5178Y cells showed that the frequency was higher when the dose was delivered chronically, which was in sharp contrast to the results by gamma-rays (Nakamura and Sawada, 1988). A subsequent study using synchronized cells revealed that the cells at G2/M stage were uniquely sensitive to mutation induction by 252Cf radiation but not so by gamma-rays (Tauchi et al, 1993). We carried out the present study to test the possibility that radiation-induced G2 block may be a major determinant of the inverse dose-rate effect following chronic 252Cf radiation. Growing cell population was first subjected to conditioning gamma or 252Cf radiation with different dose-rates, followed by cell cycle distribution analysis and 252Cf mutagenesis. We found that G2/M fraction increased by 3- to 4- fold when the conditioning doses (2 Gy of gamma or 1 Gy of 252Cf radiation) were delivered chronically over 10 hours but only slightly so when the same doses were delivered for 1 hour or less. Subsequent 252Cf irradiation gave higher mutation frequencies in the cells pre-irradiated with gamma-rays over a protracted period of time than in those with higher dose-rate gamma-rays. These results suggest that radiation-induced G2 block would be at least partly (but can not be totally) responsible for the inverse dose-rate effect. (author)