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.