Interaction of the cytotoxic and sensitizing effects of electron-affinic drugs and hyperthermia

Both published and new data on the interaction of electron-affinic drugs with hyperthermia with and without irradiation are reviewed for systems both in vitro and in vivo. Modest (sublethal) hyperthermia (41 degrees C) augments the differential hypoxic cytoxicity of some electron-affinic agents. Although hypoxic cytotoxicity increases with electron affinity, the thermal enhancement factors decrease. This finding is further evidence that hypoxic cytotoxicity and radiosensitization occur by different mechanisms. Furthermore, sublethal exposure of hypoxic cells to these agents makes them sensitive to killing by heat, which implies that because, under some circumstances, chronically hypoxic, unlike acutely hypoxic, cells can be thermally tolerant and could be important in the hyperthermic treatment of tumors