Induction of mouse liver glutathione S-transferase by ethanol

The induction of hepatic glutathione S-transferase by ethanol was investigated in male Swiss-Webster mice using a liquid diet. After a 7-day feeding period, mice that received 18, 27 or 36% of their calories as ethanol exhibited significant increases in the specific activity of glutathione S-transferase when 1,2-dichloro-4-nitrobenzene (DCNB), p-nitrobenzylchloride (NEC) and 1,2-epoxy-3-(p-nitrophenoxy)propane (ENP) were used as substrates. The observed increases in activity appeared to be related to the concentration of ethanol in the diet. Thus, mice fed a diet with 36% of the calories as ethanol exhibited the greatest increase in specific activity (DCNB, 75%; NBC, 60%, ENP, 34%). Pair-fed mice demonstrated similar changes in enzymatic activity. A time-course study indicated a 4-day feeding period was not sufficient to elicit significant induction, but a significant increase was apparent by day 7. This increase was maintained or increased through day 14. By comparison, 0.5 mg of phenobarbital/ml of diet produced a greater increase in enzymatic activity (DCNB, 449%; NBC, 227%; ENP, 219%). These results suggest that ethanol does induce glutathione S-transferase, but it is a relatively poor inducer of this enzyme.