NDLI: Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones

Content Provider	Springer Nature Link
Author	Lamarche, F. Gonthier, B. Sigrini, N. Eysseric, H. Barret, L.
Copyright Year	2004
Abstract	Ethanol consumption has long been associated with brain damage. However, the mechanism underlying this deleterious effect remains unclear. Among different hypotheses, acetaldehyde is regarded by certain authors as playing a major role in the expression of ethanol toxicity, but there are still some uncertainties about the exact nature of its implication. We therefore tried to characterize the profile of the alterations of neuronal viability and DNA integrity obtained after either a direct exposure to ethanol or to acetaldehyde. Ethanol at concentrations within the range of blood alcohol levels in intoxicated humans (≤100 mmol/L) induced DNA alterations without any apparent effect on cell viability. Acetaldehyde (≤ 1000 μmol/L) can also induce DNA alterations but with a different profile of the DNA cellular alterations. The comparison between the distributions of the comet tail DNA indicated that ethanol induced strong breaks (tail DNA ≥60 a.u.) generation whereas acetaldehyde rather induced lower breaks (20≤tail DNA ≤50 a.u.) formation but affecting a greater number of neurones. Acetaldehyde had thus a different genotoxic potential which may suggest a different mode of action or a different cellular target. Furthermore, when a single 100 mmol/L ethanol exposure did not lead to any loss of cell viability, the addition of an inhibitor of aldehyde dehydrogenase was followed by a significant loss in viability. In contrast, the inhibition of catalase, which suppresses acetaldehyde synthesis, led to no reduced viability in the same exposure conditions. ROS also reduced viability, but this was observed only after both cytochrome P450 stimulation and catalase inhibition. These combined results could suggest that acetaldehyde may play a significant role in the expression of ethanol toxicity in brain.
Starting Page	361
Ending Page	374
Page Count	14
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	20
Issue Number	6
e-ISSN	15736822
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2004-01-01
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	acetaldehyde cell culture DNA ethanol neurones SCGE Pharmacology/Toxicology Biochemistry Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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