Induction of marrow hypoxia by radioprotective agents.

The ability of thiol and non-thiol radioprotectors to induce hypoxia was determined using the binding of [3H]misonidazole by bone marrow cells as a measure of hypoxia. When administered at maximally radioprotective doses, four drugs (WR-2721, cysteamine, 5-hydroxytryptamine, and 16,16-dimethyl prostaglandin E2) significantly increased the amount of [3H]misonidazole bound by marrow cells, while no significant increase in binding was observed with three other agents (endotoxin, AET, superoxide dimutase). Doses of WR-2721 previously shown to provide suboptimal radioprotection did not significantly increase 3H-misonidazole binding. These results suggest that the physiological effects of some radioprotectors, that is, their ability to induce marrow hypoxia, may contribute to their efficacy in vivo.