Fang J L, Vaca C E
Department of Biosciences at NOVUM, Karolinska Institute, Huddinge, Sweden.
Carcinogenesis. 1997 Apr;18(4):627-32. doi: 10.1093/carcin/18.4.627.
The effect of alcohol drinking on the formation of DNA adducts of acetaldehyde, the primary oxidative metabolite of ethanol, was investigated in humans. DNA was isolated from granulocytes and lymphocytes from 24 alcoholic patients and 12 control subjects. DNA adduct levels were measured by 32P-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. A large interindividual variation in adduct levels was observed. The average adduct levels in granulocyte and lymphocyte DNA from alcoholic patients were 3.4 +/- 3.8 and 2.1 +/- 0.8 adducts/10(7) nucleotides (n = 24), respectively. These levels were 13- and 7-fold higher than the corresponding levels in control subjects (P<0.001). The average adduct level in granulocyte DNA from alcoholic patients was 60% higher than in lymphocyte DNA (P<0.01). Our results, in conjunction with the genotoxicity of acetaldehyde, thus suggest the formation of DNA adducts of acetaldehyde as a plausible mechanism explaining the involvement of alcohol drinking in carcinogenesis.
在人体中研究了饮酒对乙醇的主要氧化代谢产物乙醛形成DNA加合物的影响。从24名酒精性患者和12名对照受试者的粒细胞和淋巴细胞中分离DNA。采用反相高效液相色谱法在线检测放射性，通过32P后标记法测量DNA加合物水平。观察到加合物水平存在较大的个体间差异。酒精性患者粒细胞和淋巴细胞DNA中的平均加合物水平分别为3.4±3.8和2.1±0.8个加合物/10(7)个核苷酸(n = 24)。这些水平分别比对照受试者的相应水平高13倍和7倍(P<0.001)。酒精性患者粒细胞DNA中的平均加合物水平比淋巴细胞DNA高60%(P<0.01)。因此，我们的结果与乙醛的遗传毒性相结合，表明乙醛形成DNA加合物是解释饮酒参与致癌作用的一种合理机制。
