| Project/Area Number |
11470101
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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 |
Hygiene
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
KAWAMOTO Toshihiro University of Occupational and Environmental Health, School of Medicine, Department of Environmental Health, Professor, 医学部, 教授 (60177748)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Akiko Saga Medical School, Department of Social and Environmental Medicine, Assistant Professor, 医学部, 助手 (10330979)
ISSE Toyohi University of Occupational and Environmental Health, School of Medicine, Department of Environmental Health, Assistant Professor, 医学部, 助手 (80341494)
OYAMA Tsunihiro University of Occupational and Environmental Health, School of Medicine, Department of Environmental Health, Associate Professor, 医学部, 助教授 (00309965)
KITAGAWA Kyoko Hamamatsu University School of Medicine, 1^<st> Department of Biochemistry, Assistant Professor, 医学部, 助手 (20299605)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Acetaldehyde dehydrogenase / Knockout mice / Alcohol / Genetic Polymorphism / Alcohol preference / Acetaldehyde / Ethanol / Environmental Chemicals / エタノール嗜好性 / Cytochrome P450 2E1 / 食道癌 / 内因性オピオイド |
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| Research Abstract |
In order to study about sensitivity to environmental chemicals of individuals who lack aldehyde dehydrogenase 2 (ALDH2), Aldh2 knockout (Aldh2-/-) mouse as an animal model of ALDH2 deficient person was newly developed and subjected in this study. The results obtained in this study were as follows;
1. In vitro study of aldehyde dehydrogenase activity
Mitochondrial fractions derived from the Aldh2+/+ mice show dehydrogenase activities toward propionaldehyde, acetaldehyde and methoxyacetaldehyde. However, those from the Aldh2-/- mice did not show any dehydrogenase activities toward them.
2. Expression of drug metabolizing enzymes.
There were no differences in histological findings, expressions of mRNAs and proteins of drug metabolizing enzymes, i.e. Aldh1, Cyp1A1/2, Cyp2e1, Cyp3A4 etc., and their histological localization between the Aldh2+/+ mice and Aldh2-/- mice. However, mRNA and protein of Aldh2 in the Aldh2-/- mice were not expressed.
3. Ethanol gavage test
When ethanol (5 g/kg body weight) was administered orally, blood acetaldehyde concentrations in the Aldh2-/- mice were more than 10 time higher than those in the Aldh2+/+ mice. The AUCs (areas under the curve) of the Aldh2-/- mice were more than 20 times higher. It was also suspected that the expression levels of Cyp2e1 mRNA were different according to the Aldh2 genotypes.
4. Ethanol free-choice drinking
The Aldh2-/- mice exhibited an alcohol avoidance characteristic. After free-choice of 3% ethanol and water drinking, brain and liver acetaldehyde concentrations in the Aldh2-/- mice were almost same to those in the Aldh2+/+ mice in spite that the Aldh2-/- mice drank less ethanol than the Aldh2+/+ mice. This result indicates that the Aldh2 genotype plays an important role in alcohol preference and acetaldehyde concentration in the brain is correlated with the alcohol avoidance.
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