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Under hyperthermal conditions, some genotoxic drugs such as bleomycin, paraquat, and N-alkyl-N-nitrosoureas exhibit increased cytotoxicity toward cultured Chinese hamster V79 cells. Sequential combinations of heat and drug treatments, regardless of whether drug-exposure precedes or follows hyperthermia, also induce synergistic cytotoxicity to some extent. This may be attributed not only to the relationship of temperature and chemical injury as defined by the Arrhenius law, but also to a lethal interaction between the biological consequences of chemical injury and thermal damage. Ethanol, dimethylsulfoxide (DMSO), ethylenediaminetetraacetic acid (EDTA), and urea, which are known to affect cell membrane and protein, also exert synergistic cytotoxicity at 43 degrees C at a dose range that is nontoxic at 37 degrees C. When used sequentially with thermal treatment, they also proved to be synergistic. Glycerol, however, protected cells against thermal damage when used in a simultaneous chemical-thermal combination. But when treatments were carried out sequentially, glycerol proved destructive.

Enhanced cytotoxicity in simultaneous and sequential drug-heat treatments of cultured Chinese hamster V79 cells.