Modification of Radiation Response in Synchronized HeLa Cells by Metabolic Inhibitors: Effects of Inhibitors of DNA and Protein Synthesis

Abstract

Synchronized cultures of HeLa cells x-irradiated at different stages of the division cycle were incubated with inhibitors of DNA and protein synthesis. Thymidine at concentrations that inhibit DNA synthesis increases survival of cells irradiated in the G1-S transition of S phase when present in the medium during a 3.5-hour postirradiation period. There was no such effect of thymidine on cells irradiated in the early G1 phase. Inhibitors of DNA synthesis such as hydroxyurea, which at high concentrations are toxic even to unirradiated cells, at nontoxic concentrations will enhance survival of cells irradiated in the S phase, but will decrease survival of cells irradiated in the G1 phase. At slightly toxic concentrations, hydroxyurea enhances the effect of irradiation even in cells irradiated in the S phase. Acetoxycycloheximide, an inhibitor of both DNA and protein synthesis, increases survival in irradiated cells in a manner similar to that of thymidine, while puromycin, an inhibitor of protein synthesis d...