Muto M, Hitomi Y, Ohtsu A, Shimada H, Kashiwase Y, Sasaki H, Yoshida S, Esumi H
Department of Gastrointestinal Oncology and Gastroenterology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Int J Cancer. 2000 Nov 1;88(3):342-50.
Many epidemiological studies have identified chronic alcohol consumption as a significant risk factor for cancer of the upper aerodigestive tract (UAT) in human. Although acetaldehyde, the first metabolite from ethanol by alcohol dehydrogenase (ADH), is regarded as a carcinogen, how systemic production of acetaldehyde particularly affects the UAT remains unclear. In our study, we searched for the regional source of acetaldehyde in UAT, especially the involvement of bacteria in the human normal oral microflora. Here we demonstrate that, among the bacterial species identified from the human oral cavity, genus Neisseria had extremely high ADH activity and produced significant amounts of acetaldehyde when cultured with medium containing ethanol in vitro. The ability to produce acetaldehyde was more than 100-fold higher than that produced by any other genera we studied. Furthermore, alcohol ingestion influences the bacterial composition of the oral microflora, resulting in an increased proportion of Neisseria. Although Neisseria present in normal oral microflora is generally non-pathogenic, these findings suggest that this microbe can be a regional source of carcinogenic acetaldehyde and thus potentially play an important role in alcohol-related carcinogenesis in human UAT.
许多流行病学研究已确定长期饮酒是人类上消化道(UAT)癌症的一个重要风险因素。虽然乙醛是乙醇经乙醇脱氢酶(ADH)作用产生的第一种代谢产物,被视为一种致癌物,但乙醛的全身生成如何特别影响上消化道仍不清楚。在我们的研究中,我们寻找上消化道中乙醛的区域来源,特别是人类正常口腔微生物群中细菌的作用。在这里我们证明,在从人类口腔中鉴定出的细菌物种中,奈瑟菌属具有极高的ADH活性,并且在体外与含乙醇的培养基一起培养时会产生大量乙醛。其产生乙醛的能力比我们研究的任何其他属高出100多倍。此外,摄入酒精会影响口腔微生物群的细菌组成,导致奈瑟菌属的比例增加。虽然正常口腔微生物群中的奈瑟菌通常无致病性,但这些发现表明,这种微生物可能是致癌乙醛的区域来源,因此可能在人类上消化道与酒精相关的致癌过程中发挥重要作用。