IADR Abstract Archives
Chronic Alcohol Consumption may Enhance Carcinogenesis via Modulation of Aldehyde Dehydrogenases.
Objectives: Oral carcinogenesis is a poorly understood process. Epithelial dysplasia are cells with abnormal growth, loss of normal maturation and an increased likelihood for progression to squamous cell carcinoma. Alcohol consumption is a known risk factor for OC but the exact mechanism by which it exerts its effects is unknown. We hypothesise that alcohol may contribute to the malignant transformation of dysplastic oral cells by modulating ALDH isoform expression. Utilising gingival and buccal squamous cell carcinoma cell lines along with a dysplastic cell line, the effect of chronic alcohol treatment on the expression of ethanol-metabolising enzymes, migratory capacity and subsequent responses to acetaldehyde concentrations found in vivo were determined.
Methods: Cells were treated with ethanol (1% v/v) ‘chronically’ (2 wk) or ‘acutely’ (24 h). ADH and ALDH activity and expression was determined by enzyme assay and RT-PCR. Cells were subjected to ‘scratch’ assays, whereby a linear scratch is created in the cell monolayer and the time taken for cells to close the gap is indicative of cells migratory and invasive capacities.
Results: The oral cell lines used possess unique expression profiles of ADH and ALDH isoforms. Chronic alcohol exposure was found to decrease expression of ALDH2 and ALDH3 isoforms in DOK and TR146 cells, while simultaneously increasing ALDH1A1 in DOK cells only. Chronic alcohol exposure triggered changes in cell migration behaviour and enhanced cell proliferation following acetaldehyde treatment in dysplastic DOK cells.
Conclusions: Alcohol exposure may increase the risk for both the transformation of dysplastic cells and metastasis of oral cancer via ALDH modulation. ALDH may be a potential therapeutic target to prevent transformation of dysplasia. Similarly, ALDH expression profiles of patients may be a useful biomarker in determining those at higher risk for oral carcinogenesis.
Methods: Cells were treated with ethanol (1% v/v) ‘chronically’ (2 wk) or ‘acutely’ (24 h). ADH and ALDH activity and expression was determined by enzyme assay and RT-PCR. Cells were subjected to ‘scratch’ assays, whereby a linear scratch is created in the cell monolayer and the time taken for cells to close the gap is indicative of cells migratory and invasive capacities.
Results: The oral cell lines used possess unique expression profiles of ADH and ALDH isoforms. Chronic alcohol exposure was found to decrease expression of ALDH2 and ALDH3 isoforms in DOK and TR146 cells, while simultaneously increasing ALDH1A1 in DOK cells only. Chronic alcohol exposure triggered changes in cell migration behaviour and enhanced cell proliferation following acetaldehyde treatment in dysplastic DOK cells.
Conclusions: Alcohol exposure may increase the risk for both the transformation of dysplastic cells and metastasis of oral cancer via ALDH modulation. ALDH may be a potential therapeutic target to prevent transformation of dysplasia. Similarly, ALDH expression profiles of patients may be a useful biomarker in determining those at higher risk for oral carcinogenesis.