To identify molecular pathways responsible for the cell cycle effects of ethanol exposure in the presence of mitotic regulators, mouse Affymetrix gene expression arrays were run (Hicks et al. 2010). Expression analysis with TGFb1-treated cultures identified 569 differentially-regulated transcripts; 446 of them were downregulated (78%). Within FGF2 treated cultures, ethanol caused a significant downregulation of 122 out of 195 differentially-regulated transcripts (63%), with the single greatest change in gene clusters related to DNA replication and checkpoint associated transcripts, including the mRNA encoding cyclin (Ccn), a key G1/S checkpoint protein. Ethanol treatment in the presence of TGFb1 led to downregulation of transcripts with aggregated functions including regulation of the G1/S transition. The fact that ethanol treatment caused downregulation of a large proportion of genes and that many are associated with cell cycle control supports the hypothesis that ethanol may be affecting repressive epigenetic events such as methylation.
