Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones
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 (< or = 100 mmol/L) induced DNA alterations without any apparent effect on cell viability. Acetaldehyde (< or = 1000 micromol/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 > or = 60 a.u.) generation whereas acetaldehyde rather induced lower breaks (20 < or = tail DNA < or = 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.
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Acetaldehyde in the brain alters DNA integrity and neuronal viability; it can form AA-DNA adducts in the brain and peripheral blood leukocytes of people with AUD since ethanol, acetaldehyde, and lipid aldehydes such as MDA and 4-HNE can inhibit DNA repair enzymes; dual mechanisms of elevated AA-DNA adducts and suppressed DNA repair may contribute to genetic instability and DNA mutations, promoting
“The presence of acetaldehyde in the brain also alters DNA integrity and neuronal viability.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [197]
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- Authors
- Lamarche, F., Gonthier, B., Signorini, N., Eysseric, H., & Barret, L.
- Affiliations
- Université Joseph Fourier (FR)
- Venue
- Cell Biology and Toxicology
- Published
- 2004-11
- Volume
- 20
- Issue
- 6
- Pages
- 361-374
- ISSN
- 0742-2091 (ISSN-L)
- 1573-6822
- OpenAlex
- W2001611656
- Cited by
- 31
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 1 · 2019: 1 · 2016: 1 · 2015: 4
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Biology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ethanol toxicity, acetaldehyde, neuronal viability, DNA damage, genotoxicity, aldehyde dehydrogenase inhibition, catalase, reactive oxygen species, cytochrome P450, brain damage, alcohol intoxication
- MeSH terms
- Acetaldehyde, Ethanol, Amitrole, Animals, Brain, Cell Survival, Cells, Cultured, DNA, DNA Damage, Dose-Response Relationship, Drug, Embryo, Mammalian, Methylene Blue, Neurons, Phenobarbital, Rats, Sprague-Dawley, Comet Assay, Rats
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