The interaction of misonidazole with radiation, chemotherapeutic agents, or heat: a preliminary report.
Survival of hypoxic cells exposed to misonidazole at 37 degrees C show an initial lag period after which survival decreases exponentially with time. Hypoxic cells incubated with misonidazole for a time equivalent to that of the lag period on the survival curve show increased sensitivity when subsequently given x-irradiation. This is consistent with previously published observations. In addition, preincubation of hypoxic cells with misonidazole ata 37 degrees C also renders cells more sensitive to subsequent treatments by heat or melphalan, mustine and cis-Pt(II). Preincubation must be in hypoxia for cells to become sensitive to a second insult; preincubation in air does not change cellular sensitivity even when this preexposure is 5 mM misonidazole for 3 days. The potential of exploiting a physiological property of most solid tumors, viz., hypoxia, in order to increase sensitivity of tumor cells to cytotoxic agents is discussed.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D006358:Hot Temperature; D000860:Hypoxia / Q000378:metabolism; D008466:Mechlorethamine / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D008920:Misonidazole / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents
D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008466:Mechlorethamine; D008920:Misonidazole; D002945:Cisplatin; D008558:Melphalan