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

Abstract

Purpose: To determine quantitatively the influence of altering proliferation 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 was established by colony forming assay. Survival data were fitted to the linear-quadratic model and analyzed on the basis of the mean inactivation dose, D.

Results: Increased S-phases were associated with increased resistance to X-rays. Radiosensitivity as expressed by D differed by a factor of 1.6 between the most sensitive and the most resistant populations. Separately analyzing the alpha and beta coefficients of survival curves revealed that the proliferation dependent effect was correlated only with beta. The major determinant of D was alpha, but its substantial interexperimental 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 consequence 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.