| Abstract
| - Polychlorinated biphenyls (PCBs) are important persistent environmental contaminants. PCBs can bemetabolically converted to their hydroxylated metabolites (OHPCBs), and in recent years, these OHPCBshave been observed to inhibit human sulfotransferases (SULTs) such as the phenol SULTs (SULT family-1) involved in the metabolism of estrogen and various other endogenous and xenobiotic phenols. In thepresent study, we have investigated the hypothesis that OHPCBs interact with family 2 hydroxysteroid(alcohol) SULTs (e.g., human SULT2A1), enzymes that are physiologically important for the metabolictransformations of several key endogenous hydroxysteroids as well as xenobiotic alcohols. We haveexamined the interactions of three OHPCBs with purified recombinant human SULT2A1 (also known aseither human DHEA-ST or ST2A3). These studies with SULT2A1 were carried out on 4‘-hydroxy-2,5-dichlorobiphenyl (4‘-OH PCB 9), 4-hydroxy-2‘,3,5-trichlorobiphenyl (4-OH PCB 34), and 4‘-hydroxy-2,3‘,4,5‘-tetrachlorobiphenyl (4‘-OH PCB 68). Our results showed that 4-OH PCB 34 and 4‘-OH PCB 68were substrates for SULT2A1, and 4-OH PCB 34 exhibited substrate inhibition similar to that seen withthe physiological substrate dehydroepiandrosterone (DHEA). Although the sulfation of 4-OH PCB 34and 4‘-OH PCB 68 represents a potential metabolic route for these compounds, these OHPCBs may alsocompete with other xenobiotic substrates as well as endogenous substrates for SULT2A1. The third OHPCBstudied, 4‘-OH PCB 9, was not a substrate for SULT2A1 but was an inhibitor of the enzyme. Thus, theinteractions of OHPCBs with human SULT2A1 represent both a potential route of metabolism and apossible source of interference with sulfation reactions catalyzed by this enzyme.
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