Kim Jin Sik, Kim Yang Jee, Kim Tae Yon, Song Joo Young, Cho Yoon Hee, Park Yeong Chul, Chung Hai Won
School of Public Health and Institute of Health and Environment, Seoul National University, 28 Yunkeun-dong Chongno-ku, Seoul 110-460, Korea.
Toxicology. 2005 Jun 1;210(2-3):169-74. doi: 10.1016/j.tox.2005.01.016.
To investigate whether sensitivity to the induction of micronuclei by acetaldehyde is associated with genetic polymorphisms of the aldehyde dehydrogenase-2 (ALDH2) gene, cytokinesis-block micronucleus (CBMN) assays were performed on peripheral lymphocytes from 47 healthy human subjects exposed to acetaldehyde in vitro. Facial flushing following alcohol intake was analyzed to determine if it was correlated with ALDH2 gene polymorphisms. The frequencies of the ALDH2 genotypes ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2), and ALDH2(2)/ALDH2(2) were 66.0, 27.7, and 6.4%, respectively, in the 47 subjects. Therefore, 34% of the studied subjects carried the mutant allele ALDH2(2), which is associated with the lack of enzyme activity. The frequency of micronuclei induced by acetaldehyde increased in a dose-dependent manner with the largest increase seen in subjects that were homozygous for the ALDH2(2) allele. A significant association was observed between the ALDH2 genotype and alcohol-induced facial flushing. Average alcohol consumption of the study subjects was also associated with the ALDH2 genotype. The frequency of heavy drinking was significantly higher among subjects with the ALDH2(1)/ALDH2(1) genotype than among subjects with the ALDH2(2) allele (ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) genotypes). Alcohol-induced facial flushing was also associated with an increased frequency of micronuclei in lymphocytes treated with acetaldehyde. The results suggest that the ALDH2 genotype is significantly associated with acetaldehyde-induced micronuclei and alcohol-induced facial flushing.
为了研究对乙醛诱导微核的敏感性是否与乙醛脱氢酶2（ALDH2）基因的遗传多态性相关，对47名体外暴露于乙醛的健康人类受试者的外周淋巴细胞进行了胞质分裂阻滞微核（CBMN）检测。分析饮酒后脸红情况，以确定其是否与ALDH2基因多态性相关。在47名受试者中，ALDH2基因型ALDH2(1)/ALDH2(1)、ALDH2(1)/ALDH2(2)和ALDH2(2)/ALDH2(2)的频率分别为66.0%、27.7%和6.4%。因此，34%的研究对象携带与酶活性缺乏相关的突变等位基因ALDH2(2)。乙醛诱导的微核频率呈剂量依赖性增加，其中ALDH2(2)等位基因纯合子的受试者增加最为明显。观察到ALDH2基因型与酒精引起的脸红之间存在显著关联。研究对象的平均酒精摄入量也与ALDH2基因型相关。ALDH2(1)/ALDH2(1)基因型的受试者中重度饮酒频率显著高于携带ALDH2(2)等位基因（ALDH2(1)/ALDH2(2)和ALDH2(2)/ALDH2(2)基因型）的受试者。酒精引起的脸红还与乙醛处理的淋巴细胞中微核频率增加相关。结果表明，ALDH2基因型与乙醛诱导的微核和酒精引起的脸红显著相关。
