Additive and antagonistic effects of the radiosensitizers Ro-03-6061, diamide and nifurpipone hydrochloride when used in pairs in vitro

Three shoulder-modifying hypoxic cell radiosensitizers, the biradical nitroxyl, Ro-03-6061, diamide and nifurpipone hydrochloride, have been examined in pairs to determine their effects on hypoxic cell radiosensitivity. The effect of both the biradical and nifurpipone hydrochloride in combination with diamide was at least additive. In contrast, when the biradical and nifurpipone hydrochloride were used in combination there was no modification to the shoulder region of the hypoxic cell survival curve compared to control by hypoxic cells but there was enhanced radiosensitization at higher doses of radiation. Studies with synchronized cells suggest that ''S'' phase cells are particularly sensitive to a combination of diamide and nifurpipone. The implications of these results are discussed. (author)