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80662 
Journal Article 
Review 
DNA adducts from acetaldehyde: Implications for alcohol-related carcinogenesis 
Brooks, P; Theruvathu, J 
2005 
Yes 
Alcohol
ISSN: 0741-8329 
Alcohol 
35 
3 
187-193 
English 
16054980 
WOS:000231435900005 
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 N2-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,N2-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 DNAûprotein 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 beverageûrelated carcinogenesis. 
DNA Adducts; Mutagens; Acetaldehyde; GO1N1ZPR3B; Index Medicus; Animals; Polymorphism, Genetic -- genetics; Risk Factors; Mutagens -- toxicity; DNA Repair -- genetics; Alcohol Drinking -- adverse effects; Neoplasms -- etiology; Neoplasms -- metabolism; Alcohol Drinking -- genetics; Acetaldehyde -- toxicity; DNA Adducts -- metabolism; Acetaldehyde -- metabolism; Neoplasms -- genetics 
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