Differential proliferation dependence of alpha and beta damage in X-irradiated Chinese hamster cells

Purpose: To determine quantitatively the influence of altering proliferatio n rates on clonal survival of asynchronously growing Chinese hamster (CHO) cells after X-irradiation and to evaluate the related contribution of alpha and beta damage. Material and Methods: Cell cycle distributions at the time of X-irradiation of CHO cells were assessed by flow cytometry. Clonal radiation survival wa s established by colony forming assay. Survival data were fitted to the lin ear-quadratic model and analyzed on the basis of the mean inactivation dose , (D) over bar. Results: Increased S-phases were associated with increased resistance to X- rays. Radiosensitivity as expressed by (D) over bar differed by a factor of 1.6 between the most sensitive and the most resistant populations. Separat ely analyzing the alpha and beta coefficients of survival curves revealed t hat the proliferation dependent effect was correlated only with beta. The m ajor determinant of (D) over bar was alpha, but its substantial interexperi mental variations were independent of the cell cycle. Conclusions: Due to altering cell cycle distributions, considerable changes of radiosensitivity can occur. They can in part be understood as a consequ ence of S-phase dependent alterations of DNA damage repair. Reasons for the changes of a damage dependent lethality remain to be discovered by further research.