| Project/Area Number |
19310043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
KUNUGITA Naoki University of Occupational and Environmental Health, Japan, 生活環境部, 部長 (90178020)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Yasuhiro 産業医科大学, 医学部, 准教授 (10309958)
KAWAMOTO Toshihiro 産業医科大学, 医学部, 教授 (60177748)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2008: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | アルデヒド脱水素酵素 / 酸化ストレス / ヘモグロビン付加体 / Aldh2ノックアウトマウス / アセトアルデヒド / ミトコンドリアDNA / 体細胞突然変異 / 加齢 / 変異原性 |
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| Research Abstract |
Aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a major role in the oxidation of acetaldehyde in vivo. Half of Japanese have inactive ALDH2. In order to investigate the mutagenicity of acetaldehyde, micronucleus (MN) assay and T cell receptor (TCR) gene mutation assay were performed in Aldh2 KO mice and wild type (Aldh2 WT) mice exposed to acetaldehyde or ethanol in vivo. We also observed the urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), hemoglobin-associated acetaldehyde (Hb-AA), and mutation on tRNA gene of mitochondrial DNA. In results, frequencies of micronuclei in reticulocytes significantly increased by acetaldehyde exposure in Aldh2 KO mice, but not in Aldh2 WT mice. In addition, frequencies of micronuclei, TCR mutation, and 8-OHdG levels in urine were significantly high in Aldh2 KO mice than in Aldh2 WT mice even in control groups. These results indicate that Aldh2 plays a major role not only in acetaldehyde detoxification but also in oxidative stress in mice.
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