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 eth anol 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 u sed a squamous cell carcinoma of the head and neck (SCCHN) cell line as a m odel and, to exclude line specific effects, two other cell lines. The influ ence of ethanol on proliferation (using [H-3]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor e xpression (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 v iability (>95%) in all concentrations. In all tested cell lines, addition o f 10(-3) M ethanol caused: (a) a significant increase of cells in the S-pha se of the cell cycle; (b) a shift of cytokeratin pattern that suggested inh ibition of differentiation; and (c) significant upregulation of EGF, IL-4, and PDGF receptors. Conclusions: Our results demonstrated an increased proliferation and reduce d differentiation induced by ethanol in mucosa derived neoplastic cells, wh ich may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies .