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 degrees 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 degrees 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 degrees C, but not cis-platinum-43 degrees C, was reversed by the polyhydroxy compounds.
B A
BA
Neilan
K J
KJ
Henle
W A
WA
Nagle
A J
AJ
Moss
D001761:Bleomycin / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D004896:Erythritol / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D006358:Hot Temperature
D001761:Bleomycin; D002945:Cisplatin; D004896:Erythritol; D005690:Galactose