title: Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium.
abstract: Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N(2)-ethylidene-2'-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N(2)-ethylidene-2'-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.|Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Amanuma
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohashi
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Itatani
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Tsurumaki
authors.affiliation: Research Center for Environmental Quality Management, Kyoto University, Otsu, 520-0811, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kikuchi
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Gastroenterology Division, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Whelan
authors.affiliation: Gastroenterology Division, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Research Center for Environmental Quality Management, Kyoto University, Otsu, 520-0811, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Muto
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D004947:Esophagus; D000431:Ethanol / Q000009:adverse effects; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000431:Ethanol; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde