Heterogeneity of cytochrome P-450s induced by polychlorinated biphenyls. [Aroclor 1254]

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 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 benzphetamine N-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/sub 5/ and NADPH-cytochrome 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 delta-aminolevulinic acid synthetase and inhibition of delta-aminolevulinic acid dehydratase but no significant accumulation of porphyrins in the liver. These results clearly demonstrate that themore » polychlorinated biphenyl mixture, Aroclor 1254, possesses the inducing properties of the two main classes of microsomal enzyme inducers, namely phenobarbital and 3-methylcholanthrene.« less