Selective induction and inhibition of liver and lung cytochrome P-450-dependent monooxygenases by the PCBs mixture, Aroclor 1016.
The effects of the widely used industrial PCBs mixture, Aroclor 1016, as modifiers of monooxygenases were studied in rats and rabbits. From data presented, it is not possible to generalize the biological effects of PCBs observed with rats, namely, that they are potent, non-specific inducers of monooxygenase activities. In rat liver, Aroclor 1016 exhibited primarily the potent inducing effects of the barbiturate class of inducers. In contrast, in rabbits pretreated with Aroclor 1016, although cytochrome P-450 content of the liver was significantly increased, benzphetamine N-demethylase and benzo[a]pyrene hydroxylase activities were decreased 30-35%; and no changes in the O-deethylation of 7-ethoxycoumarin and 7-ethoxyresorufin were observed. These results strongly suggest differences in the regulation of cytochrome P-450 isozymes in the liver by the PCBs. A similar conclusion can be drawn from the pulmonary studies of Aroclor 1016-pretreated rabbits. In the lung, cytochrome P-450, form 2 and associated enzymic activities were markedly decreased, with little or no effect on the form 5 isozyme. Electrophoretic and chromatographic studies confirmed these findings. The induction and the repression of a form or forms of cytochrome P-450 by environmentally-derived chemicals may be important determinants of organ-targeted chemical toxicity.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis* / Q000378:metabolism; D002848:Chromatography, DEAE-Cellulose; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000378:metabolism; D010105:Oxygenases / Q000096:biosynthesis / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001140:Aroclors; C027386:Aroclor 1016; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase