Epidemiologic observations have implicated chronic excess ethanol consumption as a risk factor for various cancers including colon cancer. Recent epigenetic studies demonstrated that ethanol causes selective acetylation of histone H3 at lysine 9 (H3K9) in the liver, lung, spleen and testes, indicating that ethanol may inhibit histone deacetylase activity, or enhance histone acetyltransferase activity in those tissues. We therefore investigated the effect of ethanol on histone H3 modifications in colonic epithelial cells. NCM460, human colonic epithelial cells were incubated with 100mM of ethanol for 24, 48, or 72 hr and then the acetylation and methylation states of histone H3K9 were measured by immunoblot analysis using site-specific antibodies. We found that ethanol decreased acetylation of histone H3K9 in a time-dependent manner (71, 21, 17%, respectively, P<0.0001), while the histone deacetylase inhibitor, trichostatin A, which was used as a positive control, increased H3K9 acetylation. However, both ethanol and trichostatin A had little effect on histone H3K9 methylation. This is the first report of the colon-specific post-translational deacetylation of histone H3 with ethanol.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A20.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC