Molecular and Cellular PharmacologyMono- and diglucuronide formation from benzo[a]pyrene and chrysene diphenols by AHH-1 cell-expressed UDP-glucuronosyltransferase UGT1A7
Section snippets
Chemicals
6-Hydroxychrysene and chrysene-3,6-diphenol were synthesized as described [12] and identified by high-field proton NMR spectroscopy and mass spectrometry. Their purity was found to be >98%, based on HPLC analysis. BP-3,6-quinone was obtained from the Carcinogen Reference Standard Repository, National Institutes of Health (Bethesda, MD, USA).
Cells
UGT1A7-transfected AHH-1 cells were grown in culture flasks containing 50 mL RPMI 1640 medium including 1% (w/v) penicillin/streptomycin, 10% (v/v) horse
Results and discussion
MG and DG formation of both BP- and chrysene-3,6-diphenol could be clearly demonstrated in incubation mixtures containing lysates of UGT1A7-expressing cells (Table 1). Formation of these glucuronides has also been observed in UGT1A6-expressing V79 cells, with the notable exception that chrysene-3,6-diphenol DG formation was not detectable [12]. Kinetic characteristics were determined with 6-hydroxychrysene as a stable PAH phenol and compared with those found with a widely used model substrate,
Acknowledgements
The authors wish to thank the Deutsche Forschungsgemeinschaft (DFG) for financial support.
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