The objective of the research is to continue investigations on the metabolism and toxicity of halogenated hydrocarbons, which are important environmental chemicals. The studies will emphasize detailed investigations of reaction mechanisms, enzymology, and toxicology. Moreover, structure-toxicity studies will provide information about the mechanisms by which halogenated chemicals produce tissue damage and are important in enhancing the ability to predict toxic effects of chemicals.
The specific aims of the proposed research are: 1. To study the nephrotoxicity of S-conjugates of amino acids and glutathione. 2. To study the biological role and catalytic mechanism of microsomal glutathione S-transferases. 3. To study the role of episulfonium ion formation in the toxicity of vicinial-dihaloalkanes. The studies will contribute to the understanding of the mechanisms by which halogenated alkanes and alkenes produce toxicity. Biochemical and mechanistic studies with compounds that may be encountered under toxicologically relevant circumstances and with model compounds that are synthetically accessible and whose study yields much valuable information are important to establish an experimental and conceptual basis for future studies and for assessing the potential risk associated with exposure to halogenated alkanes and alkenes.
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