Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[3H]Benzo[a]pyrene (B[a]P) was administered to male Sprague-Dawley rats via intratracheal instillation, and bile was collected over a period of 6 h. Conjugated metabolites of B[a]P in bile were separated by paper chromatography or reversed-phase ion-pair HPLC and quantified by liquid scintillation spectrometry. In paper chromatographic analysis, a class of conjugates more polar than thioether conjugates was recognized. These conjugates were identified as quinol diglucuronides by hydrolyzing with beta-glucuronidase and analyzing products of the hydrolysis with HPLC, and by migration on paper relative to a standard of 3,6-quinol diglucuronide. From this analysis, relative amounts of conjugated metabolites of B[a]P in bile were 37.3% quinol diglucuronides, 19.9% thioether conjugates, 33.3% monoglucuronide and sulfate conjugates, and 9.4% unconjugated metabolites. Analysis by reversed-phase ion-pair HPLC provided improved resolution among the conjugates in bile. In particular, the 3,6-quinol diglucuronide was resolved from the 1,6- and 6,12-quinol diglucuronides, with identification of peaks being based on sensitivity to hydrolysis with beta-glucuronidase and elution of standards of these diglucuronides. The elution position of thioether conjugates was identified by their insensitivity to hydrolysis with beta-glucuronidase and arylsulfatase and by synthesis of thioether conjugates in V79 (XEM-2) cells, which express cytochrome P450IA1 and have relatively high levels of glutathione S-transferases but low levels of UDP-glucuronyltransferases and sulfotransferases. From the reversed-phase ion-pair HPLC analysis, relative amounts of conjugates in bile were 10.4% 1,6- and 6,12-quinol diglucuronides, 20.8% 3,6-quinol diglucuronide, 30.4% thioether conjugates, 17.8% monoglucuronides, 6.2% sulfate conjugates, and 14.4% unconjugated metabolites. These studies provide the first report of the biosynthesis of quinol diglucuronide conjugates of B[a]P in vivo and demonstrate that they are excreted into bile in significant quantities.
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PMID:Quinol diglucuronides are predominant conjugated metabolites found in bile of rats following intratracheal instillation of benzo[a]pyrene. 154 30

Benzo[a]pyrene (BaP) metabolism was studied in cell lines derived from rainbow trout (RTG-2), bluegill fry (BF-2), and fathead minnow (FHM). Confluent cultures were exposed to 3H-BaP (0.5 nmol/ml), and, after various exposure times, metabolites were extracted from the media with an organic solvent and analyzed by high-pressure liquid chromatography. BF-2 and RTG-2 cells converted 63% of the BaP to water-soluble metabolites within 24 h, while FHM cells converted only 12%. BF-2 and RTG-2 cells metabolized more than 90% of the BaP by 48 h, while only 67% of the BaP was converted to water-soluble metabolites by FHM cells after 96 h. The major organic-solvent-extractable metabolites in all three cell lines were 9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene and unidentified polar metabolites. Of the water-soluble metabolites formed by BF-2, FHM, and RTG-2 cells, 67, 42, and 19%, respectively, were converted to ethyl-acetate-extractable metabolites by treatment with beta-glucuronidase. All three cell lines formed a glucuronide of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol); in BF-2 and FHM cells, the 7,8-diol represented almost half of the metabolites released by beta-glucuronidase treatment. Thus, cell lines derived from three widely distributed species of freshwater fish have the capacity to metabolize BaP to a form that is a proximate carcinogen in rodents and to produce a water-soluble conjugate of this metabolite.
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PMID:Metabolism of benzo[a]pyrene by fish cells in culture. 629 Jun 79