The capacity of four cDNA-expressed human liver UDP-glucuronosyltransferases (UGT), UGT1*6, UGT2B7, UGT2B10 and UGT2B11, to glucuronidate hydroxylated metabolites of benzo[a]pyrene (B[a]P) and 2-acetylaminofluorene (AAF) has been investigated. UGT1*6 and UGT2B7 glucuronidated a range of B[a]P and AAF metabolites with a degree of regiospecificity, although UGTs 2B10 and 2B11 were inactive towards all compounds screened. UGT2B7 glucuronidated the B[a]P trans 4,5- and 7,8-dihydrodiols and the 1-,2-,4-,5-,6-,8-,9- and 10-monophenols. In contrast, UGT1*6 lacked activity towards the dihydrodiols and metabolized a more limited range of monophenols, namely 4-,5-,8- and 12-hydroxyB[a]P. Both UGT2B7 and UGT1*6 glucuronidated N, 1-,3- and 8-hydroxyAAF, but 5-hydroxyAAF was metabolised only by UGT1*6. Neither enzyme glucuronidated 3-,7- and 11-hydroxyB[a]P and 7- and 9-hydroxyAAF, although these compounds were all metabolised by human liver microsomal UGTs. The results suggest that the relative content of UGT isoforms in a cell or tissue will be important for determining the extent to which a particular carcinogen/mutagen is deactivated.
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Jin et al. (1993) studied this question.