1. 1. The total metabolism of 4-chlorobiphenyl by rat hepatic microsomes to give lipophilic phenolic products, trichloracetic acid-soluble conjugates and macromolecular-substrate adducts has been determined. 2. 2. The metabolism of this substrate by cytochrome P-450, cytochrome P-448 and mixed cytochrome P-450/P-448 induced microsomal enzymes yielded a single major phenolic product, 4′-chloro-4-biphenylol. 3. 3. Microsomal enzymes from animals pretreated with cytochrome P-448 and mixed cytochrome P-450/P-448 chemical inducers enhanced the metabolic activity whereas the activity with cytochrome P-450 induced enzymes was similar to the non-induced enzyme system. 4. 4. The unusual metabolic activity of this substrate indicated the important directive effects of the chloro substituent and suggested the potential utility of this hydroxylase assay in evaluating the effects of microsomal enzyme inducers.
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