ABSTRACT
In this chapter, the author presents data relating to their efforts and those of others to identify the metabolic events involved in the bronchiolar toxicity of 1,1-dichloroethylene and the carcinogenicity of vinyl carbamate. The paradigm that organ toxicities are mediated by metabolism and formation of reactive metabolites from chemically inert xenobiotic compounds and drugs is well established. Covalent binding is a parameter that serves as a convenient index of the formation and exposure of a tissue to reactive metabolites generated from potentially cytotoxic chemicals or drugs. Although covalent binding of electrophilic metabolites to nucleophilic sites on proteins, lipids and nucleic acids is linked to tissue cytotoxicities, some chemicals that produce reactive metabolites also produce reactive oxygen species. The cytochrome P450 monooxygenases are a superfamily of enzymes that catalyzes the oxidation of endogenous compounds such as steroids, bile acids and fatty acids, as well as a wide variety of exogenous compounds including drugs and chemicals.
