Blasiak J, Trzeciak A, Malecka-Panas E, Drzewoski J, Wojewódzka M
Department of Molecular Genetics, University of Lodz, 12/16, 90-237 Lodz, Banacha, Poland.
Toxicol In Vitro. 2000 Aug;14(4):287-95. doi: 10.1016/s0887-2333(00)00022-9.
The influence of ethanol and acetaldehyde on DNA in human lymphocytes, gastric mucosa (GM) and colonic mucosa (CM) was investigated by using the comet assay. All kinds of cells were exposed to ethanol and acetaldehyde in two regimens: the cells were incubated with either chemical and analysed or they were exposed first to ethanol, washed and then exposed to acetaldehyde and analysed. Lymphocytes were exposed to ethanol at final concentrations of 30 mM and acetaldehyde at 3 mM. GM cells were incubated with ethanol at 1 M and acetaldehyde at 100 mM. CM cells were exposed to ethanol at 10 mM and acetaldehyde at 100 mM. In combined exposure, the cells were subsequently exposed to ethanol and acetaldehyde at all combination of the concentrations of the agents. Ethanol caused DNA strand breaks, which were repaired during 4 hr, except when this agent was applied in GM cells at a concentration of 1 M. A dose-dependent decrease in the tail moment of all types of acetaldehyde-treated cells was observed. Similar results were obtained when a recognized DNA crosslinking agent, formaldehyde, was used. These results suggest that acetaldehyde may form crosslinks with DNA. These crosslinks were poorly repaired. CM cells showed the highest sensitivity of all cell types to ethanol than lymphocytes and GM cells. There were no differences in the sensitivity to acetaldehyde of all the cell types. Our results clearly indicate that ethanol and acetaldehyde can contribute to cancers of the digestive tract.
采用彗星试验研究了乙醇和乙醛对人淋巴细胞、胃黏膜(GM)和结肠黏膜(CM)中DNA的影响。所有类型的细胞均通过两种方案暴露于乙醇和乙醛:将细胞与任一种化学物质一起孵育并进行分析,或者先将细胞暴露于乙醇,洗涤后再暴露于乙醛并进行分析。淋巴细胞暴露于终浓度为30 mM的乙醇和3 mM的乙醛。GM细胞与1 M的乙醇和100 mM的乙醛一起孵育。CM细胞暴露于10 mM的乙醇和100 mM的乙醛。在联合暴露中,细胞随后以两种物质浓度的所有组合暴露于乙醇和乙醛。乙醇导致DNA链断裂,除了在GM细胞中以1 M的浓度应用该物质时,DNA链断裂在4小时内得以修复。观察到所有类型的乙醛处理细胞的尾矩呈剂量依赖性降低。当使用公认的DNA交联剂甲醛时,获得了类似的结果。这些结果表明乙醛可能与DNA形成交联。这些交联修复不佳。CM细胞在所有细胞类型中对乙醇的敏感性最高,高于淋巴细胞和GM细胞。所有细胞类型对乙醛的敏感性没有差异。我们的结果清楚地表明乙醇和乙醛可能导致消化道癌症。