| Project/Area Number |
16K09281
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
Ohashi Shinya 京都大学, 医学研究科, 助教 (20435556)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 食道癌 / 食道扁平上皮癌 / アセトアルデヒド / 発癌 / ALDH2 / ALDH2遺伝子多型 / ALDH2活性化 / Alda-1 / ヒト変異型ALDH2ノックインマウス / ALDH2活性 / DNAアダクト / 食道がん / アルコール / ALDH2活性増強 / 癌 / 食道 / 発がん予防 |
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| Outline of Final Research Achievements |
In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-dG). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice, and reduced esophageal DNA damage levels after alcohol drinking. These results indicate the protective effects of Alda-1-mediated ALDH2 activation on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism,
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| Academic Significance and Societal Importance of the Research Achievements |
食道発がんにおいてアセトアルデヒドは重要な発癌物質の一つであり、本研究成果により、ALDH2活性化剤を用いて、アルコール飲酒後の食道DNA傷害を軽減できたという結果は、将来の食道発がん予防に関する研究の重要な知見になると考えられる。
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