Increased frequencies of micronucleated reticulocytes and T-cell receptor mutation in Aldh2 knockout mice exposed to acetaldehyde
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- Kunugita Naoki
- Department of Health Information Science, School of Health Sciences, University of Occupational and Environmental Health
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- Isse Toyohi
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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- Oyama Tsunehiro
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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- Kitagawa Kyoko
- First Department of Biochemistry, Hamamatsu University School of Medicine
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- Ogawa Masanori
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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- Yamaguchi Tetsunosuke
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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- Kinaga Tsuyoshi
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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- Kawamoto Toshihiro
- Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health
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Abstract
Aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a major role in the oxidation of acetaldehyde in vivo. About half of all Japanese people have inactive ALDH2. We generated homozygous Aldh2 null (Aldh2-/-) mice by gene targeting knockout as a model of ALDH2-deficient humans. To investigate the mutagenicity of acetaldehyde, a micronucleus assay and a T-cell receptor (TCR) gene mutation assay were performed in Aldh2-/- mice and wild-type (Aldh2 +/+) mice exposed to acetaldehyde. The mice were continuously exposed to 125 and 500 ppm of acetaldehyde vapor for 2 weeks. Another group was orally administered 100 mg/kg once a day for 2 weeks continuously. The mice were killed after 2 weeks of exposure to acetaldehyde, and the frequency of micronucleated reticulocytes was measured by flow cytometry. We also observed the incidence of TCR gene mutations in T-lymphocytes by measuring the variant CD3−CD4+ expression by flow cytometry. The frequency of micronucleated reticulocytes induced by acetaldehyde was significantly increased in Aldh2 −/− mice, but not in Aldh2 +/+ mice. TCR mutant frequency was also associated with acetaldehyde exposure in Aldh2−/ − mice, especially after oral administration; however, it was not associated with acetaldehyde exposure in Aldh2 +/+ mice. In conclusion, Aldh2 −/− mice showed high sensitivity in the micronuclei and TCR mutation assays compared with Aldh2 +/+ mice after exposure to acetaldehyde.<br>
Journal
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 33 (1), 31-36, 2008
The Japanese Society of Toxicology
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Details 詳細情報について
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- CRID
- 1390282679879149184
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- NII Article ID
- 110006596029
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- NII Book ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL BIB ID
- 9382116
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed