TY - JOUR T1 - Effect of Long-Term Ethanol Exposure on the Acinar Distribution of Hepatic Glutathione <em>S-</em>Transferase JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1470 LP - 1474 VL - 28 IS - 12 AU - Tamara Vanhaecke AU - Kai O. Lindros AU - Teija Oinonen AU - Antoine Vercruysse AU - Vera Rogiers Y1 - 2000/12/01 UR - http://dmd.aspetjournals.org/content/28/12/1470.abstract N2 - The ability of ethanol to affect the regional distribution of individual glutathione S-transferase (GST) isoenzymes in rat liver was investigated by analyzing the expression levels in cell lysates obtained from the periportal or perivenous liver region after in situ digitonin perfusion. In control rats, a significant perivenous dominance of GST proteins and activities measured by the substrates 1-chloro-2,4-dinitrobenzene (broad spectrum), 1,2-dichloro-4-nitrobenzene (M1/M2-specific), and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (A1/A2-specific) was found. In pair-fed rats exposed to ethanol (36% of total calories) for 2 weeks, all GST activities measured were significantly increased in both acinar zones. However, the relative increase was greater in the perivenous region. The induction of the A1/A2-specific activity was the most pronounced. HPLC analysis revealed for both regions that this increase was largely confined to the A2 subunit, with only minor effects observed on the A1 subunit. At the mRNA level, the constitutive perivenous dominance of both GST A1 and GST A2 expression became more pronounced after ethanol administration. The results demonstrate that long-term ethanol exposure induces individual GST isoenzymes differently and might have a profound effect on xenobiotic-induced regional liver damage. The American Society for Pharmacology and Experimental Therapeutics ER -