Polychlorinated Biphenyls: A New Type of Inducer of Cytochrome P-448 in the Liver

Abstract

The CO-difference spectrum of microsomes from rats treated with the polychlorinated biphenyls mixture, Aroclor 1254, has an absorption maximum at 448 nm. With ethylisocyananide as the ligand for reduced microsomes, Aroclor 1254 treatment causes a shift in the 455-nm peak to 453 nm and increases the ratio of absorbance of 455 nm to that at 430 nm from 0.53, obtained with untreated rats, to 1.24. These findings are similar to those seen in rats treated with the polycyclic hydrocarbon, 3-methylcholanthrene, but differ from those that characterize cytochrome P-450 in control or phenobarbital-treated rats. Aroclor 1254 treatment results in a tripling of cytochrome P-448 content and a 10-fold increase in benzo-[a]pyrene hydroxylation. However—unlike 3-methylcholanthrene, but like the phenobarbital type of inducing agents—Aroclor 1254 treatment causes a significant enhancement of ethylmorphine N-demethylase. These data suggest that Aroclor 1254-induced cytochrome P-448 may be catalytically different from the 3-methylcholanthrene-induced P-448 or that the hemoprotein(s) induced by Aroclor 1254 may be a mixture of cytochromes P-448 and P-450 exhibiting catalytic properties of both cytochromes.