Formation of Toxic Intermediates in Fetal Tissues
Pharmacological actions and toxic effects of drugs and other foreign compounds are often mediated by metabolites of the administered compounds rather than by the unchanged compounds themselves. For example, bromobenzene and other halogenated hydrocarbons are converted to reactive epoxides by the action of a drug-oxidizing monooxygenase system in the liver and other tissues, with resultant liver injury (1,2). Most carcinogenic substances, e.g., acetaminofluorene and polycyclic aromatic hydrocarbons, are not carcinogenic per se, but have to be transformed into reactive electrophiles, which attack critical target molecules, thus initiating carcinogenesis (3). Many halogenated hydrocarbon pesticides are converted by microsomal enzymes into epoxides, which generally are more toxic than the parent compounds. These examples point to the considerable importance of drug-oxidizing enzyme systems in the toxic effects of xenobiotics.
KeywordsPolycyclic Aromatic Hydrocarbon Fetal Liver Fetal Tissue Polycyclic Hydrocarbon Fetal Liver Cell
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