Repair of Potentially Lethal Damage in X-Irradiated HeLa Cells

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Abstract
Treatment of synchronous populations of HeLa S3 cells with the DNA inhibitors fluorodeoxyurtdine or hydroxyurea immediately after irradiation with 220-kv X-rays in the dose range 300 to 600 rads causes a decrease in the fraction of surviving cells. Postirradiation incubation at 29[degree] C produces a similar result. Cells show quantitatively similar responses to these treatments throughout G1, their capacity to respond persisting for about 5 hr. after irradiation. The effect of temperature and hydroxyurea increases with the duration of treatment up to at least 12 hr. None of the treatments affects the viability of unirradiated cells. It is postulated that these treatments inhibit a process, ordinarily operating in irradiated cells, whereby potentially lethal damage is repaired. This repair process may involve some type of DNA synthesis. The relation of the presumptive potentially lethal damage to sublethal damage is unknown. In contrast, cyclo-heximide, an inhibitor of protein synthesis, increases survival when administered to cultures after irradiation; it apparently enhances the repair process, perhaps by inhibiting a competing process by which the potentially lethal damage is ordinarily expressed in the cell. In addition, the increase in survival brought about by treatment with cycloheximide is greater in cells irradiated in late Gl than in cells exposed in early G1. This suggests that the increase in radiation sensitivity accompanying progression of cells of this strain through G1 is the result of an increasingly favorable outcome of the expression process as compared to the repair process.