The induction of hepatic microsomal UDP-glucuronosyltransferase by the methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats

The effects of nine methylsulfonyl (MeSO(2)) metabolites of tetra-, penta- and hexachlorinated biphenyls (tetra-, penta- and hexaCBs; 20 micromol/kg once daily for 4 days) on the hepatic microsomal UDP-glucuronosyltransferase (UDP-GT) were investigated in male Sprague-Dawley rats. Each of the seven 3-MeSO(2)-PCBs, 3-MeSO(2)-2, 2',4',5-tetraCB (3-MeSO(2)-CB49), 3-MeSO(2)-2,3',4',5-tetraCB (3-MeSO(2)-CB70), 3-MeSO(2)-2,2',3',4',5-pentaCB (3-MeSO(2)-CB87), 3-MeSO(2)-2,2',4',5,5'-pentaCB (3-MeSO(2)-CB101), 3-MeSO(2)-2,2',3', 4',5,6-hexaCB (3-MeSO(2)-CB132), 3-MeSO(2)-2,2',3',4',5,5'-hexaCB (3-MeSO(2)-CB141), 3-MeSO(2)-2,2',4',5,5',6-hexaCB (3-MeSO(2)-CB149) and 4-MeSO(2)-2,2',4',5,5'-pentaCB (4-MeSO(2)-CB101) increased the activities of UDP-GT toward chloramphenicol, 4-nitrophenol and 4-methylumbelliferone. 4-MeSO(2)-2,2',4',5,5',6-hexaCB (4-MeSO(2)-CB149) increased the activity of UDP-GT toward chloramphenicol (UGT2B1) but not toward 4-nitrophenol (UGT1A6) and 4-methylumbelliferone (UGT1A6). The activity of UDP-GT toward thyroxine (T(4)) significantly increased after the administration of each of the seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101. Significant correlation was found between the activity of UDP-GT toward T(4) and serum total T(4) concentration after the administration of each of the MeSO(2) derivatives except 4-MeSO(2)-CB149. In conclusion, seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101 induce both UGT2B1 and UGT1A6, and 4-MeSO(2)-CB149 induces UGT 2B1. The results from the present study indicate that increase in the hepatic T(4) glucuronidation after the administration of the seven 3-MeSO(2)-PCBs and 4-MeSO(2)-CB101 possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum T(4) levels.