@article {Liu1065, author = {Yungang Liu and Jason T. Smart and Yang Song and Hans-Joachim Lehmler and Larry W. Robertson and Michael W. Duffel}, title = {Structure-Activity Relationships for Hydroxylated Polychlorinated Biphenyls as Substrates and Inhibitors of Rat Sulfotransferases and Modification of These Relationships by Changes in Thiol Status}, volume = {37}, number = {5}, pages = {1065--1072}, year = {2009}, doi = {10.1124/dmd.108.026021}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) are inhibitors and substrates for various human sulfotransferases (SULTs). Although the rat is often used in toxicological studies on PCBs, the interactions of OH-PCBs with rat SULTs are less well understood. In the present study, 15 OH-PCBs were investigated as potential substrates or inhibitors of purified recombinant rSULT1A1 and rSULT2A3, the major family 1 and family 2 SULTs present in rat liver, respectively. None of these OH-PCBs were substrates for rSULT2A3, 11 weakly inhibited rSULT2A3-catalyzed sulfation of dehydroepiandrosterone, and 4 had no effect on the reaction. With rSULT1A1, 4-OH-PCB 8, 4'-OH-PCB 3, 9, 12, 35, and 6'-OH-PCB 35 were substrates, whereas 4'-OH-PCB 6, 4-OH-PCB 14, 4'-OH-PCB 25, 4'-OH-PCB 33, 4-OH-PCB 34, 4-OH-PCB36, 4'-OH-PCB 36, 4'-OH-PCB 68, and 4-OH-PCB 78 inhibited the sulfation of 2-naphthol catalyzed by this enzyme. OH-PCBs with a 3,5-dichloro-4-hydroxy substitution were the most potent inhibitors of rSULT1A1, and the placement of chlorine atoms in the ortho- and meta-positions on either ring of para-OH-PCBs resulted in significant differences in activity as substrates and inhibitors. The specificity of rSULT1A1 for several inhibitory OH-PCBs was altered by pretreatment of the enzyme with oxidized glutathione (GSSG). Four OH-PCBs that were inhibitors of rSULT1A1 under reducing conditions became substrates after pretreatment of the enzyme with GSSG. This alteration in specificity of rSULT1A1 for certain OH-PCBs suggests that conditions of oxidative stress may significantly alter the sulfation of some OH-PCBs in the rat. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/37/5/1065}, eprint = {https://dmd.aspetjournals.org/content/37/5/1065.full.pdf}, journal = {Drug Metabolism and Disposition} }