ENHANCEMENT OF CYSTEAMINE CYTO-TOXICITY BY HYPERTHERMIA AND ITS MODIFICATION BY CATALASE AND SUPEROXIDE-DISMUTASE IN CHINESE-HAMSTER OVARY CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 3911-3915
Abstract
Chinese hamster ovary cells were exposed to the sulfhydryl compound cysteamine at concentrations ranging from 0-8 mM for 120 min. No toxicity was found in cells maintained at 5.degree. during treatment; however, at 37.degree. and 44.degree. a paradoxical toxicity was observed, i.e., substantial toxicity was observed at cysteamine concentrations of 0.2-1 mM but decreased at higher drug concentrations. When drug-treated cells were exposed to a 30-min a 44.degree.-heat treatment (surviving fraction, 0.15 in the absence of drug) toxicity was markedly enhanced. At 0.4 mM cysteamine, the surviving fraction was .apprx. 0.6 at 5.degree., 0.01 at 37.degree. and 0.00008 when the 44.degree.-heat treatment was also used. Cysteamine toxicity was not modified by the addition of superoxide dismutase (10 .mu.g/ml) but was completely blocked by the addition of catalase (50 .mu.g/ml) over the drug concentration range of 0.2-2.0 mM. Cysteamine autoxidation as measured by O2 uptake at 0.4 mM proceeds through H2O2 production as evidenced by the regeneration of O2 on the addition of catalase. At 4.0 mM cysteamine, O2 regeneration was not pronounced. The production of H2O2 apparently is the 1st reaction step in the mechanism of cysteamine toxicity. The subsequent production of highly reactive O2 species like hydroxyl radicals (.cntdot.OH) from H2O2 in the presence of reduced metal (Fenton chemistry) probably leads to the observed cellular toxicity.