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Int. J. Mol. Sci. 2017, 18(9), 1943; doi:10.3390/ijms18091943

Molecular Mechanisms of Acetaldehyde-Mediated Carcinogenesis in Squamous Epithelium

1
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
2
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
3
Research Center for Environmental Quality Management, Kyoto University, Otsu 520-0811, Japan
*
Author to whom correspondence should be addressed.
Received: 28 July 2017 / Revised: 29 August 2017 / Accepted: 7 September 2017 / Published: 10 September 2017
(This article belongs to the Special Issue DNA Injury and Repair Systems)
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Abstract

Acetaldehyde is a highly reactive compound that causes various forms of damage to DNA, including DNA adducts, single- and/or double-strand breaks (DSBs), point mutations, sister chromatid exchanges (SCEs), and DNA–DNA cross-links. Among these, DNA adducts such as N2-ethylidene-2′-deoxyguanosine, N2-ethyl-2′-deoxyguanosine, N2-propano-2′-deoxyguanosine, and N2-etheno-2′-deoxyguanosine are central to acetaldehyde-mediated DNA damage because they are associated with the induction of DNA mutations, DNA–DNA cross-links, DSBs, and SCEs. Acetaldehyde is produced endogenously by alcohol metabolism and is catalyzed by aldehyde dehydrogenase 2 (ALDH2). Alcohol consumption increases blood and salivary acetaldehyde levels, especially in individuals with ALDH2 polymorphisms, which are highly associated with the risk of squamous cell carcinomas in the upper aerodigestive tract. Based on extensive epidemiological evidence, the International Agency for Research on Cancer defined acetaldehyde associated with the consumption of alcoholic beverages as a “group 1 carcinogen” (definite carcinogen) for the esophagus and/or head and neck. In this article, we review recent advances from studies of acetaldehyde-mediated carcinogenesis in the squamous epithelium, focusing especially on acetaldehyde-mediated DNA adducts. We also give attention to research on acetaldehyde-mediated DNA repair pathways such as the Fanconi anemia pathway and refer to our studies on the prevention of acetaldehyde-mediated DNA damage. View Full-Text
Keywords: acetaldehyde; DNA adduct; esophageal squamous cell carcinoma; head and neck squamous cell carcinoma; DNA damage; cancer development; DNA repair pathway acetaldehyde; DNA adduct; esophageal squamous cell carcinoma; head and neck squamous cell carcinoma; DNA damage; cancer development; DNA repair pathway
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Mizumoto, A.; Ohashi, S.; Hirohashi, K.; Amanuma, Y.; Matsuda, T.; Muto, M. Molecular Mechanisms of Acetaldehyde-Mediated Carcinogenesis in Squamous Epithelium. Int. J. Mol. Sci. 2017, 18, 1943.

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