Homann N, Tillonen J, Meurman J H, Rintamäki H, Lindqvist C, Rautio M, Jousimies-Somer H, Salaspuro M
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, PL 345, Tukholmankatu 8F, 00029 HYKS, Finland.
Carcinogenesis. 2000 Apr;21(4):663-8. doi: 10.1093/carcin/21.4.663.
The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.
上消化道酒精相关致癌作用背后的发病机制仍不清楚，因为酒精本身并不致癌。然而，越来越多的证据表明，酒精的促肿瘤作用的主要部分可能是通过其第一种有毒且致癌的代谢产物乙醛介导的。乙醛由上皮细胞中的黏膜乙醇脱氢酶将乙醇转化产生，但更高水平的乙醛来自口腔微生物群对乙醇的氧化。在本研究中，我们调查了可能改变口腔微生物群组成和数量，进而影响微生物乙醛产生的因素。通过问卷调查从326名具有不同社会背景和健康状况（如口腔恶性肿瘤）的志愿者那里获取了有关牙齿健康、吸烟习惯、饮酒情况及其他因素的信息。收集石蜡诱导的唾液，并测量微生物从乙醇产生乙醛的情况。吸烟和大量饮酒是增加微生物乙醛产生的最强因素。牙齿状况不佳是否会改变乙醇在局部产生乙醛的情况仍未得到解答。细菌分析显示，主要是革兰氏阳性需氧菌和酵母菌与较高的乙醛产生有关。吸烟者和大量饮酒者中由于乙醇导致局部微生物唾液乙醛产生增加，可能是酒精和吸烟对上消化道癌症所观察到的协同致癌作用的生物学解释。它为这些解剖部位的乙醇相关致癌作用提供了一种新的微生物学研究方法。
