INDUCTION OF HEPATIC-MICROSOMAL DRUG-METABOLIZING-ENZYMES BY METHYLSULFONYL METABOLITES OF POLYCHLORINATED BIPHENYL CONGENERS IN RATS

The effect of methylsulphonyl (MeSO(2)) metabolites of 2,3',4', 5-tetrachlorobiphenyl (tetraCB) (IU-70), 2,2',3',4',5-pentachlorobiphenyl (pentaCB) (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and 2,2',3',4',5,5' -hexachlorobiphenyl (hexaCB) (IU-141), on the hepatic microsomal drug-metabolizing enzyme system was investigated in rats. The administration of 3-MeSO(2)-2,3',4',5-tetraCB (10 mu mol/kg), 3-MeSO(2)-2,3',4',5-pentaCB (0.5 mu mo/kg), 3-MeSO(2)-2,2',4',5,5'-pentaCB (0.5 mu mol/kg) and 3-MeSO(2)-2,2',3',4',5,5'-hexaCB (2 mu mol/kg) to rats significantly increased the contents of cytochromes P-450 and b(5), and the activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and benzo[a]pyrene hydroxylase. From these results, it is suggested that the 3-MeSO(2) derivatives studied are possibly potent phenobarbital-like inducers of microsomal drug-metabolizing enzymes. On the other hand, 4-MeSO(2)-2,3',4',5-tetraCB, 4-MeSO(2)-2,2',3',4',5-pentaCB, 4-MeSO(2)-2,2',4',5,5'-pentaCB and 4-MeSO(2)-2,2',3',4',5,5'-hexaCB had almost no effect on both cytochrome contents and these enzyme activities. After 96 h, following administration of 2,3',4',5-tetraCB, 2,2',3 ',4',5-pentaCB, 2,2',4',5,5'-pentaCB and 2,2',3 ',4',5,5'-hexaCB (342 mu mol/kg each), significant increases in contents of these two cytochromes and in activities of these enzymes were observed. The relationship between liver concentrations of 3-MeSO(2)-PCBs after administration of four PCB congeners and that after administration of their 3-MeSO(2) derivatives, and increases in the contents of both cytochromes and activities of drug-metabolizing enzyme suggests that the 3-MeSO(2) metabolites derived from PCBs studied play an important role in the induction of the drug-metabolizing enzymes by the parent PCB congeners.