Effects of ethanol treatment of proliferation and differentiation in a head and neck squamous cell carcinoma cell line.
BACKGROUND
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 [3H]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 [3H]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.
Kornfehl
J
J
Department of Otorhinolaryngology, General Hospital, University of Vienna, Austria.
Temmel
A
A
Formanek
M
M
Knerer
B
B
D000818:Animals; D002294:Carcinoma, Squamous Cell; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006258:Head and Neck Neoplasms; D006801:Humans; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D017978:Receptors, Growth Factor; D000431:Ethanol