The Limits to Radioprotection of Chinese Hamster V79 Cells by WR-1065 under Aerobic Conditions

Clonogenic survival and drug content for Chinese hamster V79-171 cells incubated in suspension with WR-1065 prior to γ irradiation have been determined. Factors that might influence the radioprotection by WR-1065 were investigated in control studies. Intracellular drug levels studied ranged between 0-36 nmol per 10⁶ cells. In control studies, it was established that extracellular drug toxicity was not significant for cells in suspension at 10⁶ per milliliter over short periods but was important when residual drug was present above 2 μM in the final plating of cells. Accumulation of intracellular drug above 30 nmol per 10⁶ cells produced significant cytotoxicity in unirradiated cells. Irradiation with doses as high as 150 Gy produced no significant change in the total drug level or the thiol/disulfide ratio, either for the drug in the cells or for the drug in the medium. Preirradiation with 8 Gy did not change the ability of cells to import the drug but did appear to increase the cytotoxicity of the intracellular drug at levels above 25 nmol per 10⁶ cells. There was no qualitative difference in the ability of WR-1065 to protect viable cells preirradiated with 8 Gy compared with protection of unirradiated cells. For a given γ-ray dose from 2 to 40 Gy, there is a limiting value for surviving fraction which cannot be increased by further elevation of the intracellular drug level in V79-171 cells. Such limiting radioprotection was demonstrated for HT-29/SP-1d, HeLa, Me-180-VCII and OV-2008-VI human tumor cells.