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 develop...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1986-05, Vol.46 (5), p.2245-2247
Main Authors: NEILAN, B. A, HENLE, K. J, NAGLE, W. A, MOSS, A. J
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Bleomycin - toxicity
Cell Survival - drug effects
Cells, Cultured
Cisplatin - toxicity
Erythritol - pharmacology
Galactose - pharmacology
General aspects
Hot Temperature
Medical sciences
Pharmacology. Drug treatments
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Summary: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.
ISSN:0008-5472
1538-7445