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Benzo(a)pyrene metabolism in hepatic microsomes from female DA rats with a genetic sparteine oxidation deficiency
Authors:E Schlede  I Roots
Affiliation:1. Max von Pettenkofer Institut, Bundesgesundheitsamt, BerlinFRG;1. Institut für Klinische Pharmakologie, Klinikum Steglitz, Freie Universität Berlin, Hindenburgdamm 30, D-1000 Berlin 45, F.R.G.
Abstract:The impact of the genetic hydroxylation deficiency described for several drugs such as sparteine, debrisoquine, and phenformin, has been studied with respect to benzo(a)pyrene (BP) metabolite formation. 14C-BP (80 microM) was incubated with liver microsomes from female DA rats deficient in sparteine oxidation; microsomes from female Sprague-Dawley rats served as controls. BP metabolites were separated by high pressure liquid chromatography (HPLC). No significant differences were detected in the overall formation rate of 9,10-,4,5-, and 7,8-dihydrodiol-BP, of 4 quinones, or of 9-OH- and 3-OH-BP. Thus, the study suggested no association between genetic hydroxylation polymorphism (debrisoquine/sparteine type) and the formation of at least 6 BP metabolites.
Keywords:Benzo(a)pyrene metabolism  genetic hydroxylation polymorphism (sparteine/ debrisoquine type)  pharmacogenetics  DA rat  cytochrome P-450  AHH  aryl hydrocarbon hydroxylase  BP  benzo(a)pyrene  HPLC  high pressure liquid chromatography
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