Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium

Yusuke Amanuma; Shinya Ohashi; Yoshiro Itatani; Mihoko Tsurumaki; Shun Matsuda; Osamu Kikuchi; Yukie Nakai; Shin'Ichi Miyamoto; Tsunehiro Oyama; Toshihiro Kawamoto; Kelly A. Whelan; Hiroshi Nakagawa; Tsutomu Chiba; Tomonari Matsuda; Manabu Muto

doi:10.1038/srep14142

Protective role of ALDH₂ against acetaldehyde-derived DNA damage in oesophageal squamous epithelium

Yusuke Amanuma, Shinya Ohashi, Yoshiro Itatani, Mihoko Tsurumaki, Shun Matsuda, Osamu Kikuchi, Yukie Nakai, Shin'Ichi Miyamoto, Tsunehiro Oyama, Toshihiro Kawamoto, Kelly A. Whelan, Hiroshi Nakagawa, Tsutomu Chiba, Tomonari Matsuda, Manabu Muto

Cancer Signaling and Microenvironment (CSM)

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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 N² -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 N² -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 N² -ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH₂ against acetaldehyde-derived DNA damage.

Original language	English
Article number	14142
Pages (from-to)	14142
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep14142
State	Published - Sep 16 2015

Keywords

Acetaldehyde/toxicity
Aldehyde Dehydrogenase, Mitochondrial
Aldehyde Dehydrogenase/genetics
Animals
DNA Damage/drug effects
Esophagus
Ethanol/adverse effects
Gene Expression
Humans
Keratinocytes/drug effects
Male
Mice
Mice, Knockout
Mucous Membrane/drug effects

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Amanuma, Y., Ohashi, S., Itatani, Y., Tsurumaki, M., Matsuda, S., Kikuchi, O., Nakai, Y., Miyamoto, SI., Oyama, T., Kawamoto, T., Whelan, K. A., Nakagawa, H., Chiba, T., Matsuda, T., & Muto, M. (2015). Protective role of ALDH₂ against acetaldehyde-derived DNA damage in oesophageal squamous epithelium. Scientific Reports, 5, 14142. Article 14142. https://doi.org/10.1038/srep14142

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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 N2 -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 N2 -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 N2 -ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.",

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author = "Yusuke Amanuma and Shinya Ohashi and Yoshiro Itatani and Mihoko Tsurumaki and Shun Matsuda and Osamu Kikuchi and Yukie Nakai and Shin'Ichi Miyamoto and Tsunehiro Oyama and Toshihiro Kawamoto and Whelan, {Kelly A.} and Hiroshi Nakagawa and Tsutomu Chiba and Tomonari Matsuda and Manabu Muto",

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month = sep,

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doi = "10.1038/srep14142",

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AU - Amanuma, Yusuke

AU - Ohashi, Shinya

AU - Itatani, Yoshiro

AU - Tsurumaki, Mihoko

AU - Matsuda, Shun

AU - Kikuchi, Osamu

AU - Nakai, Yukie

AU - Miyamoto, Shin'Ichi

AU - Oyama, Tsunehiro

AU - Kawamoto, Toshihiro

AU - Whelan, Kelly A.

AU - Nakagawa, Hiroshi

AU - Chiba, Tsutomu

AU - Matsuda, Tomonari

AU - Muto, Manabu

PY - 2015/9/16

Y1 - 2015/9/16

N2 - 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 N2 -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 N2 -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 N2 -ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.

AB - 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 N2 -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 N2 -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 N2 -ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.

KW - Acetaldehyde/toxicity

KW - Aldehyde Dehydrogenase, Mitochondrial

KW - Aldehyde Dehydrogenase/genetics

KW - Animals

KW - DNA Damage/drug effects

KW - Esophagus

KW - Ethanol/adverse effects

KW - Gene Expression

KW - Humans

KW - Keratinocytes/drug effects

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Mucous Membrane/drug effects

UR - http://www.scopus.com/inward/record.url?scp=84942064450&partnerID=8YFLogxK

U2 - 10.1038/srep14142

DO - 10.1038/srep14142

M3 - Article

C2 - 26374466

SN - 2045-2322

VL - 5

SP - 14142

JO - Scientific Reports

JF - Scientific Reports

M1 - 14142

ER -

Protective role of ALDH₂ against acetaldehyde-derived DNA damage in oesophageal squamous epithelium

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Keywords

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