Cited by 382Carcinogens and Genotoxicity AssessmentDNA Repair MechanismsAlcohol Consumption and Health Effects

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DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis

Brooks, Philip J., Theruvathu, Jacob A.·2005·Alcohol

DOI 10.1016/j.alcohol.2005.03.009

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Abstract

Alcoholic beverage consumption is classified as a known human carcinogen, causally related to an increased risk of cancer of the upper gastrointestinal tract. The formation of acetaldehyde from ethanol metabolism seems to be the major mechanism underlying this effect. Acetaldehyde is carcinogenic in rodents and causes sister chromatid exchanges and chromosomal aberrations in human cells. The best-studied DNA adduct from acetaldehyde is N(2)-ethyl-2'-deoxyguanosine, which is increased in liver DNA obtained from ethanol-treated rodents and in white blood cells obtained from human alcohol abusers. However, the carcinogenic relevance of this adduct is unclear in view of the lack of evidence that it is mutagenic in mammalian cells. A different DNA adduct, 1,N(2)-propano-2'-deoxyguanosine (PdG), can also be formed from acetaldehyde in the presence of histones and other basic molecules. PdG has been shown to be responsible for the genotoxic and mutagenic effects of crotonaldehyde. The PdG adduct can exist in either of two forms: a ring-closed form or a ring-opened aldehyde form. Whereas the ring-closed form is mutagenic, the aldehyde form can participate in the formation of secondary lesions, including DNA-protein cross-links and DNA interstrand cross-links. The formation of these types of complex secondary DNA lesions resulting from PdG may explain many of the observed genotoxic effects of acetaldehyde described above. Repair of PdG and its associated adducts is complex, involving multiple pathways. Inherited variation in the genes encoding the proteins involved in the repair of PdG and its secondary adducts may contribute to susceptibility to alcoholic beverage-related carcinogenesis.

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Authors: Brooks, P. J., & Theruvathu, J. A.
Affiliations: National Institutes of Health (US)
Corresponding author: Brooks, Philip J.
ORCID: Brooks, Philip J.
Venue: Alcohol
Publisher: Elsevier BV
Published: 2005-04
Volume: 35
Issue: 3
Pages: 187-193
ISSN: 0741-8329 (ISSN-L)
DOI: 10.1016/j.alcohol.2005.03.009
OpenAlex: W1990884838
Cited by: 382
References: 53
Citations by year: 2026: 15 · 2025: 10 · 2024: 18 · 2023: 18 · 2022: 23 · 2021: 16 · 2020: 18 · 2019: 19 · 2018: 21 · 2017: 19 · 2016: 19 · 2015: 12 · 2014: 22 · 2013: 26 · 2012: 25
FWCI: 5.89
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Alcohol (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: acetaldehyde, DNA adducts, crotonaldehyde, DNA-protein crosslinks, interstrand cross-links, sister chromatid exchange, chromosomal abnormalities, DNA repair, genetic susceptibility, upper gastrointestinal cancer, alcohol metabolism
MeSH terms: Acetaldehyde, Alcohol Drinking, Animals, DNA Repair, Humans, Mutagens, Neoplasms, Polymorphism, Genetic, Risk Factors, DNA Adducts

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DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis

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