Epigenetic modifications in rat pancreas following ethanol abuse.

Abstract

Chronic consumption of alcohol can lead to pancreatitis, which can predispose to pancreatic cancer. Because combinations of histone modifications have been implicated in pancreatic tumorigenesis, our goal is to find histone modifications in pancreatic acinar cell nuclei following by ethanol abuse. As an animal model of alcoholism, alcohol preferring (P) rats and alcohol non-preferring rats (NP) were used. Histones were extracted from rat pancreatic nuclear fractions using 0.4 N sulfuric acid and dialysis. Histone modifications were studied by Western-blotting analysis using the following antibodies: anti-trimethyl-histone H3 at Lys9 (H3K9me3), anti-dimethyl-histone H3 at Lys9, anti-phospho-histone H3 at Ser10, anti-acetyl-histone H3 atLys14, anti-histone H3, anti-acetyl-histone H4, anti-histone H4. We found that alcohol abuse caused a decrease in the phosphorylation of histone H3. This result was observed in pancreatic tumor specimens.Further studies are needed to determine the extentto which both modifications are related and which gene expression is affected.