Effects of ethanol treatment on proliferation and differentiation in a head and neck squamous cell carcinoma cell line

Introduction: Epidemiologic studies have provided evidence that chronic ethanol consumption is an independent risk factor in upper aerodigestive tract cancer, but the underlying mechanisms are largely unknown. Methods: To examine ethanol effects on mucosal keratinocytes in vitro, we used a squamous cell carcinoma of the head and neck (SCCHN) cell line as a model and, to exclude line specific effects, two other cell lines. The influence of ethanol on proliferation (using [H-3]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor expression (using FACS analyses) was investigated. Results: Ethanol increased in a dose dependent manner (tested range 10(-3) M to 10(-10) M) the [H-3]thymidine uptake and cell number, with unaltered viability (>95%) in all concentrations. In all tested cell lines, addition of 10(-3) M ethanol caused: (a) a significant increase of cells in the S-phase of the cell cycle; (b) a shift of cytokeratin pattern that suggested inhibition of differentiation; and (c) significant upregulation of EGF, IL-4, and PDGF receptors. Conclusions: Our results demonstrated an increased proliferation and reduced differentiation induced by ethanol in mucosa derived neoplastic cells, which may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies.