Heterogeneity of cytochrome P-450s induced by polychlorinated biphenyls.

The polychlorinated biphenyl mixture, Aroclor 1254, is a powerful inducer of both cytochromes P-450 and P-448 exhibiting the catalytic properties of both cytochromes in the liver. Addition of Aroclor 1254 to hepatic microsomes produces a type I difference spectrum. When administered to rats, the hemeprotein induced by Aroclor 1254 displayed spectral properties which are a combination of the spectral properties of the two cytochromes. The absorption maximum of the CO complex of the hemeprotein, the ratio of the 455 to 430 nm peaks of the ethyl isocyanide complex, and the pH intercepts obtained by the dependence of these peaks on the pH are intermediate between those obtained with cytochromes P-450 and P-448. Partially purified hemeproteins from Aroclor 1254-treated rats exhibited a CO spectrum with an absorption maximum at 448 nm. The catalytic properties of the induced hemeproteins are a combination of the catalytic properties of cytochrome P-450 induced by phenobarbital and of cytochrome P-448 induced by 3-methylcholanthrene in rats. The biphenyl mixture markedly enhanced the cytochrome P-450-associated enzymes, including the ethylmorphine and benzphetamineN-demethylases and the hexobarbital oxidative pathway. Similarly, the cytochrome P-448 enzymic activities, including the hydroxylation of benzo(a)pyrene and of zoxazolamine were greatly enhanced. Aroclor 1254 also increased cytochrome b, and NADPHcytochrome c reductase activity of liver microsomes. Enhancement of benzo(a)pyrene hydroxylase activity occurred in nonhepatic tissues, including lung, kidney, adrenals, intestine, and testis. Acute exposure of rats to Aroclor 1254 resulted in a small but significant induction of Gaminolevulinic acid synthetase and inhibition of 6-aminolevulinic acid dehydratase but no significant accumulation of porphyrins in the liver. These results clearly demonstrate that the polychlorinated biphenyl mixture, Aroclor 1254, possesses the inducing properties of the two main classes of microsomal enzyme inducers, namely phenobarbital and 3-methylcholanthrene.