Polychlorinated biphenyls, classified as either phenobarbital- or 3-methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor promoters in diethylnitrosamine-initiated rats.
The cytochrome P-450 isozymes, cytochrome P-450 MC1 and MC2, purified from rats treated with 3-methylcholanthrene (MC), were found by immunohistochemical staining to be strongly induced in the livers of rats treated with 3,3', 4,4'-tetrachlorobiphenyl (TCBP), while the cytochrome P-450 isozymes, PB1 and PB2, purified from the livers of rats treated with phenobarbital (PB), were shown to be induced in the livers of rats treated with 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCBP). The latter compound also strongly induced NADPH-cytochrome P-450-reductase. Following induction, all 5 enzymes were located preferentially in the centrilobular and midzonal region of the liver acinus. The influence of these polychlorinated biphenyls (PCBs) on diethylnitrosamine (DEN)-initiated hepatocarcinogenesis was investigated by analyzing the evolution of adenosine triphosphatase-deficient focal lesions. Whereas DEN alone produced very few islets, the administration of either PCB congener (150 mumol/kg, i.p., once weekly over a period of 8 weeks) subsequent to DEN treatment (50 ppm in the drinking water, 10 days) strongly enhanced the number of islets as well as the relative volume of liver occupied by islet tissue. These effects were evident, both 1 and 9 weeks, after cessation of PCB treatment. Unexpectedly the less persistent PCB congener, TCBP, showed a much more potent enhancing effect after the 9 weeks recovery period than did (HCBP).
D000818:Animals; D003043:Cocarcinogenesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004052:Diethylnitrosamine; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats
D007527:Isoenzymes; D004052:Diethylnitrosamine; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl; D010634:Phenobarbital; C014024:2,4,5,2',4',5'-hexachlorobiphenyl