Accession Number : ADA238790


Title :   Free Radical Mechanisms of Xenobiotic Mammalian Cytotoxicities


Descriptive Note : Final rept.,


Corporate Author : GEORGE WASHINGTON UNIV MEDICAL CENTER WASHINGTON DC DEPT OF MEDICINE


Personal Author(s) : Dickens, Benjamin F.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA238790


Report Date : 30 JUN 1991


Pagination or Media Count : 38


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.


Descriptors :   *MEASUREMENT , MEMBRANES(BIOLOGY) , CHEMICALS , CELLS , TOXICITY , LIPIDS , IRON , OXIDATION , DOSAGE , PHYSIOLOGY , MUSCLES , FREE RADICALS , CELLS(BIOLOGY) , CARDIOVASCULAR SYSTEM , CHLORINATED HYDROCARBONS , TRICHLOROETHYLENE , TRICHLOROETHANES , ENDOTHELIUM , CHLOROETHANES , CARBON TETRACHLORIDE , CATALASE , MANNITOL , VOLUME


Subject Categories : MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE