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 presence 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1991
- Accession Number
- ADA238790
Entities
People
- Benjamin F. Dickens
Organizations
- George Washington University