ACUTE EXPOSURE OF CULTURED NEURONES TO ETHANOL RESULTS IN REVERSIBLE DNA SINGLE-STRAND BREAKS; WHEREAS CHRONIC EXPOSURE CAUSES LOSS OF CELL VIABILITY

Aims: 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 uncertain ties 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 th an 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, neu rones entered a death cell process compatible with apoptosis.