Radioprotection by WR-2721 in vitro at low oxygen tensions: implications for its mechanisms of action.

Radioprotection of spheroids of Chinese hamster V79 cells by WR-2721 was found to be a function of spheroid size, with the greatest dose-modifying effect by the protector observed for spheroids almost large enough to contain radioresistant "anoxic" cells. The nature of the response suggested that most of the protective effect was due to the presence of an increased hypoxic fraction in the drug-treated spheroids. Similarly, when single-cell suspensions were irradiated at various oxygen tensions, one component of radioprotection by WR-2721 was found to be highly dependent upon the available oxygen. Two mechanisms of radioprotection of V79 cells by WR-2721 were thus demonstrated: a modest, oxygen-independent effect, presumably due to hydrogen donation, and an oxygen-depleting effect, which is of maximal significance for cells or tissues which would otherwise be partially sensitized by low levels of oxygen.