THE LIMITS TO RADIOPROTECTION OF CHINESE-HAMSTER V79 CELLS BY WR-1065UNDER AEROBIC CONDITIONS

Clonogenic survival and drug content for Chinese hamster V79-171 cells incubated in suspension with WR-1065 prior to gamma irradiation have been determined. Factors that might influence the radioprotection by W R-1065 were investigated in control studies. Intracellular drug levels studied ranged between 0-36 nmol per 10(6) cells. In control studies, it was established that extracellular drug toxicity was not significa nt for cells in suspension at 10(6) per milliliter over short periods but was important when residual drug was present above 2 mu M in the f inal plating of cells. Accumulation of intracellular drug above 30 nmo l per 10(6) cells produced significant cytotoxicity in unirradiated ce lls. Irradiation with doses as high as 150 Gy produced no significant change in the total drug level or the thiol/disulfide ratio, either fo r 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 d id appear to increase the cytotoxicity of the intracellular drug at le vels above 25 nmol per 10(6) cells. There was no qualitative differenc e in the ability of WR-1065 to protect viable cells preirradiated with 8 Gy compared with protection of unirradiated cells. For a given gamm a-ray dose from 2 to 40 Gy, there is a limiting value for surviving fr action which cannot be increased by further elevation of the intracell ular drug level in V79-171 cells. Such limiting radioprotection was de monstrated for HT-29/SP-1d, HeLa, Me-180-VCII acid OV-2008-VI human tu mor cells. (C) 1998 by Radiation Research Society.