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 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.
Bock
K W
KW
Institute of Toxicology, University of Tübingen, Germany. bock@uni-tuebingen.de
Raschko
F T
FT
Gschaidmeier
H
H
Seidel
A
A
Oesch
F
F
Grove
A D
AD
Ritter
J K
JK
D001564:Benzo(a)pyrene / Q000378:metabolism*; D002460:Cell Line; D002911:Chrysenes / Q000378:metabolism*; D005965:Glucuronates / Q000032:analysis / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D006923:Hymecromone / Q000378:metabolism; D007700:Kinetics; D010636:Phenols / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D002911:Chrysenes; D005965:Glucuronates; D010636:Phenols; D001564:Benzo(a)pyrene; C087203:6-hydroxychrysene; D006923:Hymecromone; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7