Similarities in Cellular Inactivation by Hyperthermia or by Ethanol

The question of how cells are inactivated by mild hyperthermia (41 to 45/sup 0/C) is difficult to resolve because heat stresses most (if not all) cellular organelles. As a result, studies showing correlations between cell death resulting from heat exposure and damage to specific subcellular units tend to be inconclusive. We have looked for a heat analog, i.e., another agent whose mode of cell inactivation closely resembles that of heat. Our hypothesis is that information about the mechanism of cell inactivation closely resembles that of heat. Our hypothesis is that information about the mechanism of cell inactivation by this agent should aid in identifying the targets for heat inactivation. Here we report results that we interpret as showing that ethanol may be such an analog. Exposure of cells to heat or ethanol induces tolerance to heat, ethanol, or adriamycin. The cytotoxicity of both ethanol and heat is enhanced by low pH and cysteamine; it is reduced by deuterium oxide. Finally, treating cells either before or after x irradiation with either agent enhances cell killing.