Effect of long-term ethanol exposure on the acinar distribution of hepaticglutathione S-transferase

The ability of ethanol to affect the regional distribution of individual gl utathione S-transferase (GST) isoenzymes in rat liver was investigated by a nalyzing the expression levels in cell lysates obtained from the periportal or perivenous liver region after in situ digitonin perfusion. In control r ats, a significant perivenous dominance of GST proteins and activities meas ured by the substrates 1-chloro-2,4-dinitrobenzene (broad spectrum), 1,2-di chloro-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 (3 6% of total calories) for 2 weeks, all GST activities measured were signifi cantly increased in both acinar zones. However, the relative increase was g reater in the perivenous region. The induction of the A1/A2-specific activi ty was the most pronounced. HPLC analysis revealed for both regions that th is 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 afte r ethanol administration. The results demonstrate that long-term ethanol ex posure induces individual GST isoenzymes differently and might have a profo und effect on xenobiotic-induced regional liver damage.