The effect of GSH depletion on thermal radiosensitization

Chinese hamster ovary (CHO) cells were heated at 420 and/or irradiated in order to assess the role of intracellular glutathione (GSH) on aerobic thermal radiosensitization. GSH was titrated to various steady state levels by exposure to various concentrations of diethylmaleate (DEM). Analysis of dose-response curves indicated that GSH depletion affected thermal sensitization and thermal radiosensitization only when greater than 95% of the GSH had been depleted. Thermal enhancement ratios (TER), calculated for cells heated 10 minutes after irradiation, indicated that depletion of 80% of the intracellular GSH increased the TER by only 5%. Extensive GSH depletion (<95%) increased the TER by 18%. GSH depletion also increased the fixation of radiation damage. For example, survival after 10 Gy decreased from 0.012 to 0.055 if CHO cells were incubated in 100 μm DEM at 370 for 2 hours after irradiation. The results show that GSH is an important agent for the protection of cells against thermal enhancement of radiation damage