Molecular Pharmacology, Vol 13, 521-532, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Properties of Purified Liver Microsomal Cytochrome P450 from Rats Treated with the Polychlorinated Biphenyl Mixture Aroclor 1254

¹ Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110

Hepatic microsomal cytochrome P450 has been purified from rats treated with Aroclor 1254 to a specific content of greater than 19.0 nmoles/mg of protein and compared with purified cytochromes P450 from phenobarbital- and 3-methylcholanthrene-treated rats. Cytochrome P450 from Aroclor 1254-treated rats cannot be distinguished from a mixture of hemeproteins from phenobarbital- and 3-methylcholanthrene-treated rats by its spectral and catalytic properties or its electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels. The cross-reactivity of cytochrome P450 from Aroclon 1254-treated rats with antibodies prepared against the hemeproteins from phenobarbital- or 3-methylcholanthrene-treated rats has also been examined. On Ouchterlony double-diffusion plates the cross-reaction of the Arocbor 1254-inducible cytochrome P450 with either antibody is indistinguishable from the reaction of a mixture of hemeproteins from phenobarbital- and 3-methylcholanthrene-treated rats. When the antibody to cytochrome P450 from 3-methylcholanthrene-treated rats is used to inhibit metabolism, no differences are observed between cytochrome P450 from Aroclor 1254-treated rats and a mixture of hemeproteins from phenobarbital- and 3-methylcholanthrene-treated rats. However, the effects of the antibody to cytochrome P450 from phenobarbital-treated rats on the metabolism of 7-ethoxycoumarin and benzo[a]pyrene suggest that the hemeprotein preparation from Aroclor 1254-treated rats may differ in certain antigenic properties from a mixture of cytochromes P450 from phenobarbital-and 3-methylcholanthrene-treated rats.

Note:
ACKNOWLEDGMENTS We thank Drs. A. H. Conney and A. Y. H. Lu for their suggestions during the course of this work, and Ms. Susan B. West for the preparation of the NADPH-cytochrome c reductase. We also thank Ms. Candace Caso for her help in preparation of the manuscript.