Enhanced cytotoxicity of antineoplastic agents following prolonged exposure to misonidazole

Chinese hamster V79 cells cultured in vitro were used to investigated the cytotoxicity of various anti-cancer drugs subsequent to a prolonged treatment of the cells with Misonidazole (MISO). The sensitivity of the cells to Bleomycin (BLM), Melphalan or cis-Platinum (cis-DDP) was significantly increased by prior incubation with MISO under hypoxic conditions. When cysteamine, a radical scavenger, was present during the pretreatment with MISO, this enhancement of cytotoxicity was greatly reduced. These experiments, suggest that MISO by virtue of its selective toxicity towards hypoxic cells and its enhancement of cell killing by anti-neoplastic drugs, can play an important role in cancer chemotherapy.