Cytotoxic effects of hyperthermia and adriamycin on Chinese hamster cells

Chinese hamster cells, exposed to simultaneous hyperthermia (43 degrees C) and adriamycin (ADM), were intially sensitized to the cytotoxic activity of ADM. If the duration of the combined treatment exceeded about 30 minutes, however, the cells became refractory to additional killing by ADM. If heat was applied before ADM exposure, the cells also could be rendered insensitive; this state persisted so that 24 hours after a 50-minute exposure to 43 degrees C, the cells still showed considerable resistance to ADM. The most reasonable explanation for the findings was that cell membrane permeability to ADM was initially increased by hyperthermia, but prolonged (greater than 30 min) heat exposure reversed this situation and inhibited additional ADM from penetrating to sensitive sites. However, the data yield no hints as to the precise mechanisms involved nor are they sufficiently precise to exclude other explanations. The results do point to precautions that must be observed if the combination of ADM and hyperthermia is to be used clinically.