Formation of mono- and diglucuronides and other glycosides of benzo( a)pyrene-3,6-quinol by V79 cell-expressed human phenol UDP-glucuronosyltransferases of the UGT1 gene complex

Abstract

Glucuronidation of quinols of polycyclic aromatic hydrocarbons (PAHs) represents an important detoxication pathway preventing toxic quinone/quinol redox cycles. Therefore, mono- and diglucuronide formation of benzo( a)pyrene-3,6-quinol was investigated and compared to that of structurally related 3,6-dihydroxychrysene and simple phenols (1-naphthol and 4-methylumbelliferone) using V79 cell-expressed human UGT1.6 (= P1) and human UGT1.7 (= P4). Properties of human UGT1.6 were compared to those of the rat ortholog. Cofactors related to UDP-glucuronic acid such as UDP-galacturonic acid and UDP-glucose were also studied. It was found that rat and human UGT1.6 and human UGT1.7 catalyse monoglucuronide formation of planar PAH quinols. Diglucuronide formation was only detectable with human UGT1.7. The UGT isozymes studied also formed galacturonides and, although only to a minor extent, glucosides. Rat UGT1.6 (but not the human ortholog) catalysed digalacturonide formation of benzo( a)pyrene-3,6-quinol; the in vivo significance of galacturonide formation remains to be established. The results suggest that planar PAH phenols and quinols are conjugated more efficiently by human UGT1.7 than by UGT1.6, which preferentially conjugates simple planar phenols.