Metabolism of benzo(a)pyrene by lung microsomes from rabbits pretreated with polychlorinated biphenyls and 2,3,4,7,8-pentachlorodibenzofuran.
The polychlorinated biphenyls (PCBs) mixture, Aroclor 1254, is a weak inducer of aryl hydrocarbon hydroxylase (AHH) activity in rabbit lung. In contrast, 2,3,4,7,8-pentachlorodibenzofuran (PCDF), like 3-methylcholanthrene (3-MC), caused a 3-fold increase in pulmonary AHH activity. An important finding of the present studies was that AHH activity, whether assayed by the flourometric or HPLC methods, was dependent on the buffer used in the incubation mixture. The metabolism of benzo(a)pyrene (BP) to its oxidative metabolites, as assayed by HPLC, revealed that PCBs, PCDF and 3-MC pretreatments caused greater than 15-fold and about 3- to 4-fold increase in the formation of the tumorigenic metabolites 9,10- and 7,8-dihydrodiols, respectively. In contrast to 3-MC and PCDF, PCBs caused a 75% decrease in the formation of the K-region metabolite, BP-4,5-dihydrodiol. These studies strongly suggest that the catalysis of BP metabolism is mediated by more than one isoform of cytochrome P450 (P450).
Ueng
T H
TH
Department of Pharmacology, Uniformed Services University, Bethesda, MD 20814-4799.
Alvares
A P
AP
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001572:Benzofurans / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D011817:Rabbits
D001140:Aroclors; D001572:Benzofurans; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C038890:2,3,4,7,8-pentachlorodibenzofuran