Yokoyama Akira, Tsutsumi Eri, Imazeki Hiromi, Suwa Yoshihide, Nakamura Chizu, Mizukami Takeshi, Yokoyama Tetsuji
National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan.
Alcohol Clin Exp Res. 2008 Sep;32(9):1607-14. doi: 10.1111/j.1530-0277.2008.00739.x. Epub 2008 Jul 8.
Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers.
In a randomized cross-over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3-week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking.
The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 microM in saliva vs. 2 to 5 microM in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 microM in saliva vs. 12 to 25 microM in blood), and they were 13 to 25 microM higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes.
There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype.
乙醛被怀疑在上消化道(UADT)癌症发展中起关键作用。饮酒后唾液中乙醛水平升高部分归因于口腔细菌产生乙醛。一些酒精饮料,尤其是苹果白兰地和烧酒,含有非常高的乙醛水平。乙醛脱氢酶-2(ALDH2)基因杂合失活会增加饮酒者患UADT癌症的风险。
在一项随机交叉设计研究中,19名健康的日本志愿者在空腹条件下,每隔3周分别摄入以13%乙醇苹果白兰地、13%乙醇烧酒、13%乙醇红酒和5%乙醇啤酒形式存在的0.6 g乙醇/千克体重。我们在饮酒后即刻以及饮酒结束后30、60、90、120和180分钟监测血液和唾液中的乙醛浓度。
每种饮料的乙醛浓度分别为:苹果白兰地0.60 mM(40%未稀释溶液中为1.86 mM),烧酒0.60 mM(25%未稀释溶液中为1.16 mM),红酒0.25 mM,啤酒0.14 mM。饮酒后即刻,唾液中乙醛浓度在饮用红酒后显著低于其他饮料,饮用啤酒后即刻显著低于苹果白兰地。饮酒后30至180分钟的乙醛浓度与饮料类型无关。在整个观察期内,所有12名ALDH2基因纯合活性个体(唾液中24至53微摩尔/升,血液中2至5微摩尔/升)和所有7名ALDH2基因杂合失活个体(唾液中37至76微摩尔/升,血液中12至25微摩尔/升)的唾液乙醛浓度均远高于血液乙醛浓度,并且在调整年龄、体重、性别、吸烟和饮酒习惯以及上次刷牙后的时间后,ALDH2基因杂合个体的唾液乙醛浓度比ALDH2基因纯合个体高13至25微摩尔/升。从唾液乙醛浓度中减去血液乙醛浓度后的数值在ALDH2基因杂合个体中也高于ALDH2基因纯合个体。
根据酒精饮料类型和ALDH2基因型,UADT暴露于高唾液乙醛浓度存在差异,这些差异部分解释了根据酒精饮料和ALDH2基因型UADT癌症易感性的差异。