Experimental radiotherapy with WR-2721 and misonidazole.

The data from a large series of experiments on mouse skin and tumors are summarized. Radioprotection with WR-2721 has been observed in both tumors and normal tissues. The protection factors are generally, but not always, higher for skin than for tumors. The protection observed in skin is greater for mice irradiated breathing air than for those irradiated in oxygen. It is postulated that the different protection factors observed in different normal tissues and tumors may reflect differences in tissue oxygenation levels. The combination of misonidazole and WR-2721 has been studied in terms of the modification of radiosensitivity and also as the modification of lethal toxicity. An interaction has been observed in all aspects. The toxicity of WR-2721 increases in the presence of misonidazole. The WR-2721 radioprotection of both skin and tumors decreases if the sensitizer is added. Likewise the radiosensitization with misonidazole is diminished when WR-2721 is present. These results indicate an interaction at the site of radiation injury and they also demonstrate that WR-2721 can adequately penetrate into hypoxic tumor cells.