Enhancement of hyperthermia-induced cytotoxicity upon ATP deprivation

The combined effects of hyperthermia and uncouplers of oxidative phosphorylation (dinitrophenol (DNP) or m-chlorocarbonylcyanide phenyl-hydrazone (CCCP) or 5-thio-d-glucose (5-TG) on mammalian cell survival were studied in vitro. Uncouplers were toxic towards cells treated under aerobic conditions at 41 degrees C, whereas 5-TG potentiated the effect of hyperthermia in the case of hypoxic cells. In aerobic conditions the intracellular ATP concentration was decreased upon action of uncouplers, and similar changes occurred in hypoxic cells treated with 5-TG. The results suggest that the ATP deprivation enhances the cell killing by hyperthermia.