| Project/Area Number |
08308032
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Graduate School of Science, Tohoku University |
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Principal Investigator |
YAMAMOTO Kazuo Graduate School of Science, Tohoku University, Professor, 大学院・理学研究科, 教授 (20093536)
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| Co-Investigator(Kenkyū-buntansha) |
IDE Hiroshi Faculty of science, Hiroshima University, Professor, 理学部, 教授 (30223126)
ISHII Naoaki Faculty of Medicine, Tokai University, Associate Professor, 医学部, 助教授 (60096196)
YUKAWA Osami National Institute of Radiological Sciences, Division of Biology, Head, 生物影響研究部第2研究室, 室長 (80166850)
YONEI Shuji Graduate School of Science, Kyoto University, Professor, 大学院理学研究科, 教授 (60093340)
KASAI Hiroshi University of Occupational and Environmental Health, Professor, 産業生態科学研究所, 教授 (40152615)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥22,900,000 (Direct Cost: ¥22,900,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1997: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1996: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | oxidative stress / active oxygen species / superoxide dismutase / OGG gene / Nth gene / GTP cyclohydrolaseII / cytochrome b / MutY protein / 5・formyl-dUTP / thymine glycol / アポトーシス誘導 / カタラーゼ欠損細胞 / 5-フォルミルウラシル / 酸化ストレス応答 / riboflavin光化学反応 / OxyR蛋白 / mutM遺伝子 / endonuclease III / endonuclease VIII / 過酸化水素細胞毒性 / Nicking assay / α-デオキシアデノシン / 生体膜脂質過酸化 |
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| Research Abstract |
Oxidative stress is emerging as one of the most important causative agents of mutagenesis, carcinogenesis, aging and a number of diseases. DNA and deoxynucleotides are potential targets for attacking by active oxygen species, and virtually all aerobic organisms have developed complex defense and repair mechanisms to mitigate the deleterious effects of active oxygen species. The first line of defense seeks to neutralize the active oxygen species themselves. This line of defense includes various enzymatic and nonenzymatic defense mechanisms such as superoxide dismutase and catalase. Active oxygen species that escape the primary defense can damage nucleic acids. The second line of defense removes DNA damage caused by active oxygen species that escape the primary defense mechanisms. Several proteins have been demonstrated to be involved in the repair of DNA lesions.
In this research project, we have examined the defense mechanisms of cell against active oxygen species. During the periods, we cloned and characterized the genes coded for mammalian repair enzymes such as OGG gene (F.coli mutM homologue) and Nth gene (E.coli nth homologue). We demonstrated that E.coli GTP cyclohydrolase II can partially hydrolyze 8-oxodGTP, a mutagenic substrate for DNA synthesis. We found that E.coli MutY protein has a Guanine-DNA glycosylase that acts on 8-oxoG : G mispair to prevent spontaneous G : C->C : G transversions. We showed that a mutation in succinate dehydrogenase cytochrome b causes oxidative stress and aging in C.elegans. We suggested that the mutations can be induced by oxidative damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP in F.coli. Including these results, we obtained more than 130 papers published in the prestigious international journals.
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