Inhibition of benzo(a)pyrene and benzo(a)pyrene 7,8-dihydrodiol metabolism by benzo(a)pyrene quinones.
نویسندگان
چکیده
Benzo(a)pyrene 1,6-, 3,6-, and 6,1 2-quinones were found to be noncompetitive inhibitors of mixed-function oxidation of benzo(a)pyrene (BP) and frans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-dihydrodiol). BP 6,1 2-quinone was the most potent inhibitor of both BP and BP-7,8-dihydrodiol oxi dation followed by BP 1,6-quinone and BP 3,6-quinone. The K, for inhibition of BP mixed-function oxidation by BP 6,1 2-qui none was 0.35 ¡IM. Metabolism of BP 7,8-dihydrodiol was more sensitive to inhibition by BP quiñones; the K¡for BP 6,12quinone was 0.10 /¿M. High-pressure liquid Chromatographie analysis indicated no effect of BP quiñoneson the distribution of BP and BP-7,8-dihydrodiol metabolites. BP quiñones were reduced by 3-methylcholanthrene-induced rat liver microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate. Under anaerobic con ditions, where reoxidation was prevented, reduction of BP quiñones was rapid and followed first-order kinetics. Under aerobic conditions, steady-state levels of reduced and oxidized quiñones were observed; BP 1,6and 3,6-quinones were 30 to 40% reduced while BP 6,12-quinone was less than 5% reduced. All three quiñones stimulated oxygen uptake by mi crosomes. Rapid reoxidation of the reduced quiñones could account for the observed levels of oxidized quinone. Homo geneous rat liver reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reducÃ-ase catalyzed reduction of the quiñones at rates consistent with those for microsomal reduction, and the rate was not enhanced by addition of ho mogeneous cytochrome P-448. The strong inhibition of BP and BP 7,8-dihydrodiol metabo lism by BP quiñonesprovides an explanation for the stimulatory effect of uridine diphosphoglucuronic acid on BP metabolism apd DMA modification by BP metabolites.
منابع مشابه
Inhibition of Benzo(a)pyrene and Benzo(a)pyrene 7,8-Dihydrodiol Metabolism by Benzo(a)pyrene Quiñones1
Benzo(a)pyrene 1,6-, 3,6-, and 6,1 2-quinones were found to be noncompetitive inhibitors of mixed-function oxidation of benzo(a)pyrene (BP) and frans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-dihydrodiol). BP 6,1 2-quinone was the most potent inhibitor of both BP and BP-7,8-dihydrodiol oxi dation followed by BP 1,6-quinone and BP 3,6-quinone. The K, for inhibition of BP mixed-function oxi...
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ورودعنوان ژورنال:
- Cancer research
دوره 39 10 شماره
صفحات -
تاریخ انتشار 1979