6533b7d4fe1ef96bd1262975

RESEARCH PRODUCT

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

Franz OeschKarl Walter BockJoseph K. RitterAlbrecht SeidelAndrew D. GroveHarald GschaidmeierFrank T. Raschko

subject

PharmacologyChrysenechemistry.chemical_classificationStereochemistryMetaboliteGlucuronidationPolycyclic aromatic hydrocarbonGlucuronatesTransfectionBiochemistryChrysenesCell LineSubstrate SpecificityKineticschemistry.chemical_compoundPhenolschemistryBenzo(a)pyreneBenzo(a)pyrenepolycyclic compoundsPyrenePhenolsGlucuronosyltransferaseHymecromoneCarcinogen

description

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 Km value (0.1 microM) than UGT1A6 (10 microM). The results suggest that the two PAH-inducible UGTs may cooperate in conjugating PAH metabolites, but that UGT1A7 is more efficient.

yearjournalcountryeditionlanguage
1999-03-01Biochemical Pharmacology
https://doi.org/10.1016/s0006-2952(98)00337-2