Takeshita T, Kawai T, Morimoto K
Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, Suita, Japan.
Cancer Res. 1997 Apr 1;57(7):1241-3.
Acetaldehyde is suspected to be the ultimate carcinogen in alcohol-related carcinogenesis. The atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have higher blood concentrations of free acetaldehyde after drinking alcohol. We measured levels of acetaldehyde reversibly bound to hemoglobin (HbAA) after drinking 0.4 ml/kg ethanol using fluorigenic high performance liquid chromatography method in volunteers with the two major ALDH2 genotypes. In the ALDH2*1/1 genotype with high ALDH2 activity, the increase of HbAA was small. By contrast, in the ALDH21/2 genotype with low ALDH2 activity, HbAA increased considerably at 1-6 h after the drink, and the elevated levels persisted up to 48 h. We also measured HbAA in 81 male workers. Although HbAA levels were significantly correlated with alcohol consumption levels in both of the ALDH2 genotypes, the slope was significantly steeper in the ALDH21/2 genotype than in the ALDH21/*1 genotype. In summary, we demonstrated for the first time a significant difference in the increase of HbAA levels after drinking alcohol, depending on the ALDH2 genotype. The HbAA levels are not only a good biomarker for increased internal exposure levels to acetaldehyde but may also be a predictive biomarker for acetaldehyde-mediated carcinogenesis.
乙醛被怀疑是酒精相关致癌过程中的最终致癌物。低 Km 醛脱氢酶（ALDH2）的非典型基因型在饮酒后血液中游离乙醛浓度较高。我们使用荧光高效液相色谱法，在具有两种主要 ALDH2 基因型的志愿者中，测量了饮用 0.4 ml/kg 乙醇后与血红蛋白（HbAA）可逆结合的乙醛水平。在具有高 ALDH2 活性的 ALDH2*1/1 基因型中，HbAA 的增加幅度较小。相比之下，在具有低 ALDH2 活性的 ALDH21/2 基因型中，饮酒后 1 - 6 小时 HbAA 显著增加，且升高水平持续至 48 小时。我们还测量了 81 名男性工人的 HbAA。虽然在两种 ALDH2 基因型中 HbAA 水平均与饮酒量显著相关，但 ALDH21/2 基因型的斜率比 ALDH21/*1 基因型显著更陡。总之，我们首次证明饮酒后 HbAA 水平的增加存在显著差异，这取决于 ALDH2 基因型。HbAA 水平不仅是乙醛体内暴露水平增加的良好生物标志物，还可能是乙醛介导的致癌作用的预测生物标志物。
