In Vivo Cytotoxicity of Misonidazole and Hyperthermia in a Transplanted Mouse Mammary Tumor

The cytotoxicity of misonidazole (miso) in vivo in unclamped tumors at hyperthermic temperatures, and in clamped tumors at hypothermic, euthermic, and hyperthermic temperatures has been examined. No cytotoxicity, measured as increased tumor control, was observed in unclamped tumors heated 30 min after systemic miso administration. This may reflect the short serum half-time of miso in the mouse and a small hypoxic fraction in this tumor system. There was, however, significant miso cytotoxicity in clamped tumors at euthermic and hyperthermic temperatures when the clamp was applied 30 min after systemic miso. The degree of cytotoxicity observed was dependent upon the temperature of incubation, the length of clamping, and the dose of miso.