Department of Pharmacology, Faculty of Pharmacy, University of Seville, C/Profesor Garcia Gonzalez 2, 41012 Sevilla, Spain.
Department of Pharmacology, Faculty of Pharmacy, University of Seville, C/Profesor Garcia Gonzalez 2, 41012 Sevilla, Spain.
Drug Alcohol Depend. 2018 Feb 1;183:201-204. doi: 10.1016/j.drugalcdep.2017.11.013. Epub 2017 Dec 27.
Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially exerts a local carcinogenic effect. Recent findings indicate that the risk of cancer in a tissue is strongly correlated with the number of stem cell divisions accumulated by the tissue; the accumulation of stem cell divisions leads to the accumulation of cancer-promoting errors such as mutations occurring during DNA replication. Since cell death activates the division of stem cells, we recently proposed that the possible cytotoxicity of ethanol on the cells lining the tissues in direct contact with alcoholic beverages could explain the local carcinogenic effect of alcohol. Here we report that short-term exposures (2-3 s) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, may be a simple and effective way to reduce the risk of cancers of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also reduce the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers.
饮酒是癌症的已知危险因素。全球近 6%的癌症归因于饮酒。其中约一半发生在高度暴露于乙醇的组织中，如口腔、咽、上喉和食管。然而，由于乙醇没有诱变作用，并且乙醇的诱变代谢物（乙醛）主要在肝脏中产生，因此不清楚为什么饮酒会优先产生局部致癌作用。最近的研究结果表明，组织发生癌症的风险与该组织中累积的干细胞分裂数量密切相关；干细胞分裂的积累导致在 DNA 复制过程中发生的突变等促进癌症的错误的积累。由于细胞死亡会激活干细胞的分裂，我们最近提出，与直接接触酒精饮料的组织细胞层接触的乙醇的潜在细胞毒性可能解释了酒精的局部致癌作用。在这里，我们报告称，在 10%至 15%的乙醇浓度范围内，短时间（2-3 秒）暴露会开始以浓度依赖性方式对人上皮角质形成细胞产生明显的细胞毒性作用。我们提出，选择含有非细胞毒性浓度乙醇的酒精饮料，或稀释乙醇至非细胞毒性浓度，可能是降低饮酒者口腔、咽、喉和食管癌症风险的简单有效方法。这种预防策略还可能降低已知的饮酒和吸烟对这些癌症风险的协同作用。
