High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects:: Strong evidence for the local carcinogenic action of acetaldehyde
High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects:: Strong evidence for the local carcinogenic action of acetaldehyde
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DOI：
10.1111/j.1530-0277.2000.tb02068.x
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发表时间：
2000-06-01
影响因子：
3.2
通讯作者：
Salaspuro, M
中科院分区：
文献类型：
--
作者：
Väkeväinen, S;Tillonen, J;Salaspuro, M
背景：由于点突变，30%至50%的亚洲人缺乏醛脱氢酶-2（ALDH 2）同工酶。在亚洲ALDH 2缺乏的重度饮酒者中，消化道癌症的风险显着增加（比值比3.4-54.2）。这是未知的原因，但可能是由于当地的致癌作用的aldehyde.Methods：唾液和血液中的乙醛水平进行了测定后，在20个健康的亚洲人中等剂量的酒精（0.5克/公斤体重）。唾液乙醛生产能力从乙醇在体外进行了测定。采用聚合酶链反应/限制性片段长度多态性方法对亚洲人的ALDH 2基因型进行检测。乙醛含量的腮腺唾液中测定在三个ALDH 2缺陷的亚洲人和三个白色主题与正常ALDH 2后相同剂量的ethanol.Results：7个亚洲人是杂合子的突变ALDH 2 *2等位基因（flushers）。在240分钟的随访期间，他们的唾液乙醛水平比ALDH 2正常的亚洲人（n = 13）高2至3倍（p < 0.001）。只有在冲洗者的腮腺有助于唾液乙醛的产生。两组唾液从乙醇中产生乙醛的体外能力是相等的。冲洗者的血液乙醛水平只有九分之一的水平在salipha.Conclusions：通过使用这种人类的“敲除模型”缺乏乙醛去除，我们发现，除了口腔微生物菌群，唾液中的乙醛也可能源于氧化乙醇在腮腺。当结合早期的流行病学数据，这些结果提供了一个强有力的证据乙醛在人类中的局部致癌作用。
Background: Due to a point mutation, aldehyde dehydrogenase-2 (ALDH2) isoenzyme is deficient in 30% to 50% of Asians. Among Asian ALDH2-deficient heavy drinkers, the risk for digestive tract cancers is markedly increased (odds ratio 3.4-54.2). The reason for this is unknown but could be due to the local carcinogenic action of acetaldehyde.Methods: Salivary and blood acetaldehyde levels were determined in 20 healthy Asians after a moderate dose of alcohol (0.5 g/kg of body weight). Salivary acetaldehyde production capacity from ethanol in vitro was measured also. ALDH2 genotype of the Asians was determined from isolated leukocyte-deoxyribonucleic acid by polymerase chain reaction/restriction fragment length polymorphism method. Acetaldehyde content of parotid gland saliva was measured in three ALDH2-deficient Asians and three White subjects with normal ALDH2 after the same dose of ethanol.Results: Seven of the Asians were heterozygous for the mutant ALDH2*2 allele (flushers). They had two to three times higher salivary acetaldehyde levels than the Asians (n = 13) with normal ALDH2 throughout the follow-up period of 240 min (p < 0.001). Only in the flushers did the parotid gland contribute to salivary acetaldehyde production. The in vitro capacity of saliva to produce acetaldehyde from ethanol was equal in both groups. The flushers' blood acetaldehyde levels were only one ninth of the levels in saliva.Conclusions: By using this human "knockout model" for deficient acetaldehyde removal, we found that in addition to oral microflora, acetaldehyde in saliva may also originate from the oxidation of ethanol in the parotid gland. When combined with earlier epidemiological data, these results offer a strong evidence for the local carcinogenic action of acetaldehyde in humans.