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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 <jats:italic>N<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>-ethylidene-2\u2032-deoxyguanosine were higher in the oesophagus of <jats:italic>Aldh<\/jats:italic>2-knockout mice than in wild-type mice upon ethanol consumption. <jats:italic>In vitro<\/jats:italic> experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the <jats:italic>N<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>-ethylidene-2\u2032-deoxyguanosine levels increased in both <jats:italic>Aldh<\/jats:italic>2-knockout mouse keratinocytes and <jats:italic>ALDH2<\/jats:italic>-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the <jats:italic>N<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>-ethylidene-2\u2032-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.<\/jats:p>","DOI":"10.1038\/srep14142","type":"journal-article","created":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T09:17:31Z","timestamp":1442395051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium"],"prefix":"10.1038","volume":"5","author":[{"given":"Yusuke","family":"Amanuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Itatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Tsurumaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukie","family":"Nakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2019ichi","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunehiro","family":"Oyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonari","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Muto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,16]]},"reference":[{"key":"BFsrep14142_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay, J. et al. 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