TRICHLORETHYLENE OXIDE AND ITS MACROMOLECULAR ADDUCTS

Vanderbilt University, Nashville TN

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Abstract

The carcinogenecity and toxicity of common pollutant trichloroethylene is well known. Oxidation not only yields reactive products that covalently bind to proteins and DNA but also leads to inactivation of cytochrome P450. Results obtained from examination of the microsomal metabolites suggest that there are a number of potentially reactive electrophiles formed during the oxidative metabolism of trichloroethylene; chloral, trichloroethanol, dichloroacetyl chloride, dichloroacetic acid, trichloroethylene oxide, glyoxylic acid, and formyl chloride. This proposal is designed to elucidate the mechanism of cytochrome P450 activation of trichloroethylene, identifying the mechanism of degradation of trichloroethylene oxide and the nature of protein adducts formed with trichloroethylene oxidation products in vitro and in vivo.