Lamarche F, Gonthier B, Signorini N, Eysseric H, Barret L
Laboratoire Oligo-éléments et Résistance au Stress Oxydant induit par les Xénobiotiques (ORSOX, UMR-E UJF/CEA), Faculté de Médecine de Grenoble, Domaine de la Merci, La Tronche, France.
Alcohol Alcohol. 2003 Nov-Dec;38(6):550-8. doi: 10.1093/alcalc/agg118.
Ethanol can create progressive neuropathological and functional alterations of neurones. However, the influence of exposure duration is still debated. It is difficult to specify the level of alcohol consumption leading to alcohol-induced brain damage. Moreover, the mechanism of toxicity is assumed to combine direct and metabolically induced effects, although numerous uncertainties remain. Finally, the genotoxic power of ethanol has not fully been investigated in the brain. In the experiment reported herein, primary cultures of neurones were exposed either chronically or acutely to doses of ethanol within the range of blood alcohol levels in intoxicated humans. The impact on the integrity of neurones was assessed by cytotoxicity tests and DNA alterations by single-cell gel electrophoresis (Comet assay) and flow cytometry. Chronic ethanol exposure, even at a low dose, was more harmful to neurones than acute exposure. Both significant reductions in cell viability and DNA alterations were observed in this condition. On the other hand, DNA repair capacities seemed to be preserved as long as the viability measured by specific tests was not affected. Instead, neurones entered a death cell process compatible with apoptosis.
乙醇可导致神经元发生进行性神经病理学和功能改变。然而，暴露持续时间的影响仍存在争议。很难确定导致酒精性脑损伤的饮酒量水平。此外，尽管仍存在许多不确定性，但毒性机制被认为是直接作用和代谢诱导作用的结合。最后，乙醇在大脑中的遗传毒性尚未得到充分研究。在本文报道的实验中，将原代神经元培养物长期或急性暴露于醉酒人类血液酒精水平范围内的乙醇剂量。通过细胞毒性试验评估对神经元完整性的影响，并通过单细胞凝胶电泳（彗星试验）和流式细胞术检测DNA改变。长期乙醇暴露，即使是低剂量，对神经元的危害也比急性暴露更大。在这种情况下，观察到细胞活力显著降低和DNA改变。另一方面，只要通过特定试验测得的活力不受影响，DNA修复能力似乎就得以保留。相反，神经元进入了与凋亡相符的死亡细胞过程。
