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.

Abstract

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.