Evidence for separate modes of action in thermal radiosensitization and direct thermal cell death

It is not known whether heat potentiation of radiation damage and direct heat death are mediated by the same or by different heat lesions within the cell. In this study, three types of experiments were performed on BP‐8 murine sarcoma cells to provide evidence against a common mode of action: (1)Evaluation of the kinetics of cell death from heat, radiation, and combined heat‐radiation treatments: direct heat death is rapid and essentially complete within 24‐48 hours after heat exposure, whereas radiation death develops only after a delay period of several days. Radiosensitization by heat affects only the delayed component of cell death, that is, the radiation component of death. (2)Thermal radiosensitization and direct heat death as a function of heating time: thermal radiosensitization requires only short exposures to heat; prolonged heating does not further enhance this effect. In contrast, direct heat death increases with increasing duration of heat exposure. (3)Independent modification of radiosensitization and thermal death: addition of 5% glycerol to the incubation medium protects cells against direct heat death, but not against thermal radiosensitization. In combination, these findings suggest that heat potentiation of radiation lethality and direct heat death are two distinct phenomena mediated by different cellular mechanisms.