Mono- and diglucuronide formation from benzo[ a]pyrene and chrysene diphenols by AHH-1 cell-expressed UDP-glucuronosyltransferase UGT1A7

Polycyclic aromatic hydrocarbon (PAH)-type compounds induce at least two rat UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT1A7. Among the glucuronidation reactions of PAH metabolites studied, mono- and diglucuronide formation of benzo[ a]pyrene and chrysene-3,6-diphenol showed the highest indu...

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Published in:Biochemical pharmacology 1999-03, Vol.57 (6), p.653-656
Main Authors: Bock, Karl Walter, Raschko, Frank T, Gschaidmeier, Harald, Seidel, Albrecht, Oesch, Franz, Grove, Andrew D, Ritter, Joseph K
Format: Article
Language:English
Subjects:
6-hydroxychrysene
Benzo(a)pyrene - metabolism
benzo[ a]pyrene-3,6-diphenol
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cell Line
Chemical agents
chrysene-3,6-diphenol
Chrysenes - metabolism
Glucuronates - analysis
Glucuronates - metabolism
glucuronidation
Glucuronosyltransferase - biosynthesis
Glucuronosyltransferase - metabolism
Hymecromone - metabolism
Kinetics
Medical sciences
Phenols - metabolism
Substrate Specificity
Transfection
Tumors
UGT1A7
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Summary:Polycyclic aromatic hydrocarbon (PAH)-type compounds induce at least two rat UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT1A7. Among the glucuronidation reactions of PAH metabolites studied, mono- and diglucuronide formation of benzo[ a]pyrene and chrysene-3,6-diphenol showed the highest induction factors in rat liver microsomes. Availability of AHH-1 cells stably expressing UGT1A7 allowed us to study whether this PAH-inducible isoform could catalyze benzo[ a]pyrene and chrysene-3,6-diphenol glucuronidation. It was found that UGT1A7 indeed catalyzed mono- and diglucuronide formation of both benzo[ a]pyrene and chrysene 3,6-diphenols. V79 cell-expressed rat UGT1A6 also catalyzed these reactions, except for chrysene diphenol diglucronide formation (Bock et al., Mol Pharmacol 42: 613–618, 1992). Enzyme kinetic studies of the glucuronidation of 6-hydroxychrysene (used as a stable PAH phenol) indicated that UGT1A7 conjugated this compound with a lower apparent K m value (0.1 μM) than UGT1A6 (10 μM). The results suggest that the two PAH-inducible UGTs may cooperate in conjugating PAH metabolites, but that UGT1A7 is more efficient.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(98)00337-2