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Molecular mechanisms of acetaldehyde-mediated carcinogenesis in squamous epithelium
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- Mizumoto, Ayaka
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University
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- Ohashi, Shinya
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University
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- Hirohashi, Kenshiro
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
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- Amanuma, Yusuke
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University
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- Matsuda, Tomonari
- Research Center for Environmental Quality Management, Kyoto University
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- Muto, Manabu
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University
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Description
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.
Journal
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 18 (9), 1943-, 2017-09-10
MDPI AG
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Keywords
Details 詳細情報について
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- CRID
- 1050282810839674880
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- NII Article ID
- 120006497359
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- ISSN
- 14220067
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- HANDLE
- 2433/233626
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- PubMed
- 28891965
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE