Singh N P, Khan A
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195, USA.
Mutat Res. 1995 Jul;337(1):9-17. doi: 10.1016/0921-8777(95)00006-6.
We evaluated the DNA damaging effects of ethanol and its major metabolite, acetaldehyde. Freshly isolated human lymphocytes from two healthy donors were incubated with 0, 1.56, 6.25, 25, and 100 mM of ethanol or acetaldehyde in complete medium for 1 h. We used a newly developed, sensitive, alkaline microgel electrophoresis technique to quantitate single- and double-strand DNA breaks or alkali-labile sites in individual cells. Ethanol did not induce DNA strand breaks. However, acetaldehyde induced both single-strand (even at the lowest concentration of 1.56 mM) and double-strand breaks (only at the highest concentration of 100 mM). Following exposure to acetaldehyde, cells were incubated in complete medium for 30, 60, and 120 min. During this incubation period, most cells were unable to repair DNA single- and double-strand breaks caused by acetaldehyde. We also observed a significant cell loss after exposure to acetaldehyde. To our knowledge, this is the first study demonstrating DNA single- and double-strand breaks by acetaldehyde.
我们评估了乙醇及其主要代谢产物乙醛对DNA的损伤作用。从两名健康供体新鲜分离的人淋巴细胞，在完全培养基中与0、1.56、6.25、25和100 mM的乙醇或乙醛孵育1小时。我们使用一种新开发的、灵敏的碱性微凝胶电泳技术来定量单个细胞中的单链和双链DNA断裂或碱不稳定位点。乙醇未诱导DNA链断裂。然而，乙醛诱导了单链断裂（即使在最低浓度1.56 mM时）和双链断裂（仅在最高浓度100 mM时）。暴露于乙醛后，细胞在完全培养基中孵育30、60和120分钟。在此孵育期间，大多数细胞无法修复由乙醛引起的DNA单链和双链断裂。我们还观察到暴露于乙醛后细胞有显著损失。据我们所知，这是第一项证明乙醛可导致DNA单链和双链断裂的研究。
