Effect of ethanol on the expression of hepatic glutathione S-transferase: An in vivo/in vitro study

Ethanol, a human toxicant and a solvent in pharmacological research, is kno wn to interfere with biotransformation of xenobiotics. We compared the in v ivo and in vitro long-term effects of ethanol exposure on the expression of glutathione S-transferases (GST, EC 2.5.1.18) in rat river. Long-term in v ivo ethanol treatment to achieve blood ethanol levels ranging between 10-50 mM was by liquid diet feeding. For in vitro experiments, rat hepatocytes c o cultured with rat liver epithelial cells were exposed to 17 and 68 mM eth anol for up to 10 days. Two weeks of liquid diet ethanol treatment increase d total GST activity. Both Mu and Alpha classes and in particular the A1 an d A2 subunits and the amount of their corresponding mRNAs were increased. T otal GST activity was also increased in co cultures after exposure to 68 mM ethanol for 10 days. However, the Mu class subunits M1 and M2 and the corr esponding mRNAs were increased, rather than the Alpha class subunits. Thus, long-term exposure to ethanol induces hepatic GST both in vivo and in, vit ro, but different isoenzymes are affected. Consequently, extrapolation of i n vitro data on GST expression and regulation to the in vivo situation must be judicious. During xenobiotic metabolism in cell culture, a shift in rel ative expression and induction of different GST forms may occur, resulting in either an under or overestimation of effects. (C) 2000 Elsevier Science Inc.