Cytotoxicity of Hyperthermia Combined with Bleomycin or cis-Platinum in Cultured RIF Cells: Modification by Thermotolerance and by Polyhydroxy Compounds

The effect of thermotolerance and of polyhydroxy compounds on the cytotoxicity of bleomycin and cis -platinum was studied in cultured RIF tumor cells. Cell survival in response to drug-heat treatments was compared in cells not previously exposed to hyperthermia and in preheated cells that had developed thermotolerance. Since cellular accumulation of polyhydroxy compounds is a potential mechanistic basis of thermotolerance, we also compared cell survival of thermotolerant cells and chemically heat-protected cells. The cytotoxicity of bleomycin and cis -platinum in control cells treated with drug plus heat (43°C, 1 h) was increased synergistically over the cytotoxicity of drug and heat alone. In thermotolerant cells, the synergistic interaction was largely reversed with the bleomycin-heat combination but retained with cis -platinum at 43°C. In the absence of heat, bleomycin and cis -platinum showed similar cytotoxicity in control and thermotolerant cells. The addition of heat protectors (erythritol or galactose) modified the drug-heat cytotoxicity similar to thermotolerance. The synergistic interaction of bleomycin-43°C, but not cis -platinum-43°C, was reversed by the polyhydroxy compounds.