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 phenobarbitaltreated rats. Aroclor 1254 treatment results in a tripling of cytochrome P-448 content and a 10-fold increase in benzo-[alpyrene 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-methylcholanthreneinduced 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.

Metabolic activation/deactivation reactions during perinatal development.

“…4-CB induces cytochrome P-448-dependent enzymes and 6-CB induces P-450-dependent pathways in livers of offspring exposed to these congeners transplacentally and during lactation. Thus, the perinatal and adult livers respond to PCBs in much the same way (64)(65)(66). Our studies demonstrate that in developing rats, like adults, individual congeners are P-450 or P-448 inducers and that neonates may be more sensitive to PCBmediated increases in enzyme activities than adults.…”

Metabolic reduction of chromium by alveolar macrophages and its relationships to cigarette smoke.

“…Experiments aiming at assessing the inducibility of Cr(VI) reduction by PAM preparations showed that the PCB Aroclor 1254, which is a potent and wide-spectrum inducer of both microsomal (35) and cytosolic (7) enzymes, stimulated in rats a slight yet significant increase in activity.…”

Xenobiotic monooxygenase activity and the response to inducers of cytochrome P-450 during embryonic and larval development in fish

“…properties of both the PB-and 3-MC-classes of inducers (Alvares ~ al., 1973;Vainio, 1974). Commerc ial preparations with higher degrees of chlorination have been found to be more potent inducers of monooxygenase activity than those of lower chlorination (Bickers et ~., 1972;Chen and DuBois, 1973).…”

“…Polychlorinated biphenyls (PCBs) are industrial chemicals that are ubiquitous and persistent environmental contaminants, and are also potent inducers of xenobiotic monooxygenase activity (Risebrough et al, 1968;Nisbet and Sarofim, 1972;Wassermann et ~., 1979;Alvares et ~., 1973). Commercial PCB mixtures are complex assemblages of chlorinated bipheny 1 congeners which act as "mixed inducers" in rats, having…”