Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells.

ABSTRACT

Although ethanol is a class I carcinogen and is linked to more than 700,000 cancer incidences, a clear understanding of the molecular mechanisms underlying ethanol-related carcinogenesis is still lacking. Further understanding of ethanol-related cell damage can contribute to reducing or treating alcohol-related cancers. Here, we investigated the effects of both short- and long-term exposure of human laryngeal epithelial cells to different ethanol concentrations. RNA sequencing shows that ethanol altered gene expression patterns in a time- and concentration-dependent way, affecting genes involved in ribosome biogenesis, cytoskeleton remodeling, Wnt signaling, and transmembrane ion transport. Additionally, ethanol induced a slower cell proliferation, a delayed cell cycle progression, and replication fork stalling. In addition, ethanol exposure resulted in morphological changes, which could be associated with membrane stress. Taken together, our data yields a comprehensive view of molecular changes associated with ethanol stress in epithelial cells of the upper aerodigestive tract.