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Alcohol & Alcoholism Vol. 38, No. 6, pp. 550-558, 2003
© 2003 Medical Council on Alcohol

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

F. Lamarche, B. Gonthier, N. Signorini, H. Eysseric and L. Barret*,

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

(Received 30 December 2002; first review notified 7 March 2003; in revised form 5 May 2003; accepted 19 June 2003)

* Author to whom correspondence should be addressed at: Fédération de Toxicologie Clinique et Biologique, CHU de Grenoble, 38 043 Grenoble Cedex, France. Tel.: +133 4 7676 5783; Fax: +133 4 7676 5177; E-mail: Luc.Barret{at}ujf-grenoble.fr

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 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.


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