Free Radical Mechanisms of Xenobiotic Mammalian Cytotoxicities
Abstract
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 presences of physiological levels of iron in these vascular cells by a mechanism that doesn't require cytochrome P-450. Antiradical treatment with deferoxamine and Probucol (but not SOD, catalase, or mannitol) appear to reduce the toxicity of these agents. We have also detected the presences of free radicals in the cultured cells by ESR spin trapping following exposure to iron and chlorinated hydrocarbons. Although this free radical production does not appear to require biotransformation by cytochrome P-450, it is also not a result of spontaneous oxidation of the IRP chemicals. Keywords: Toxicity, Cytotoxin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 30, 1989
- Accession Number
- ADA216904
Entities
People
- Benjamin F. Dickens
Organizations
- George Washington University