López-Lázaro Miguel
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
Oral Oncol. 2016 Nov;62:149-152. doi: 10.1016/j.oraloncology.2016.10.001. Epub 2016 Oct 5.
Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect may have been overlooked because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of DNA-damaging agents (e.g., acetaldehyde and tobacco carcinogens). Alcohol consumption may increase the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.
流行病学数据表明，全球5.8%的癌症死亡可归因于饮酒。饮酒时，与酒精接触最密切的组织（如口腔、咽和食管）患癌风险更高。然而，由于乙醇没有致突变性，且乙醇的致癌代谢物（乙醛）大多在肝脏中产生，所以尚不清楚为何饮酒会优先产生局部致癌作用。众所周知，乙醇在酒精饮料中的浓度会导致细胞死亡；然而，这种效应可能被忽视了，因为死细胞不会引发癌症。在此我讨论，乙醇对口腔、咽和食管内衬细胞的细胞毒性作用会激活位于黏膜更深层的干细胞进行分裂，以替代死亡细胞。每次干细胞分裂时，它们都会暴露于与细胞分裂相关的不可避免的错误（例如，DNA复制过程中出现的突变以及有丝分裂过程中发生的染色体改变），并且也极易受到DNA损伤剂（如乙醛和烟草致癌物）的基因毒性作用影响。饮酒可能通过促进维持这些组织内稳态的干细胞中细胞分裂的积累，增加患口腔、咽和食管癌的风险。了解酒精致癌的机制对于加强流行病学证据以及提高公众对饮酒与癌症之间紧密联系的认识非常重要。
