Free Radical Mechanisms of Xenobiotic Mammalian Cytotoxicities
GEORGE WASHINGTON UNIV MEDICAL CENTER WASHINGTON DC DEPT OF MEDICINE
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Our initial goal was to identify if free radical mechanisms are involved in the cytotoxicity of a number of IRP volume I and II chemicals. We found that a number of these agents act to enhance membrane lipid peroxidation in response to a standard dose of exogenous free radicals. Using chlorinated hydrocarbons carbon tetrachloride, trichloroethylene, dichloroethylene, trichloroethane, dichloroethane as a model for other IRP chemicals, we established conditions to measure lipid peroxidation in cultured smooth muscle and endothelial cells. These agents induced lipid peroxidation in the presence of physiological levels of iron in these vascular cells by a mechanism that doesnt require cytochrome P-450. Antiradical treatment with deferoxamine and probucol but not SOD, catalase, or mannitol appear to reduce the toxicity of these agents.
- Medicine and Medical Research