| Project/Area Number |
09670223
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TOYOKUNI Shinya Department of Patuology and Biology of Diseases, Graduate School of Medicine, Kyoto University Associate professor, 医学研究科, 助教授 (90252460)
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| Co-Investigator(Kenkyū-buntansha) |
HIAI Hiroshi Department of Patuology and Biology of Diseases, Graduate School of Medicine, Kyoto University Professor, 医学研究科, 教授 (10073131)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | free radical / oxidative stress / 8-hydroxy-2'-deoxyguauosive / 4-hydroxy-2-noueual / mouocloual autibody / carciuogenesis / diabetes mellitus / p15.p16 / 活性酵素 / 8-hydroxy-2'-deoxyguanosine / 4-hydroxy-2-nonenal / 活性酸素 / ディファレンシャル・ディスプレイ / 鉄 / 4-ヒドロキシ-2-ノネナール / 8-ヒドロキシ-2'-デオキシグアノシン / 免疫染色 / 4-ヒドロキシ-2-ノネナ-ル |
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| Research Abstract |
Recent studies have clarified that reactive oxygen species(ROS)are involved in a diversity of biological phenomena including radiation damage, carcinogenesis, ischemia-reperfusion injury, diabetes mellitus and neurodegenerative diseases. In this project we have established methods to localize ROS-induced damage in paraffin-embedded specimens. This owes to a successful production of antibodies against covalently modified structures specific for ROS-induced damage. The epitopes include 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins. This technique was applied to animal models of human specimens of diabetes mellitus, reperfusion injury, arsenic intoxication, colon cancer, viral hepatitis as well as oxidative stress-induced cancer model of rats using ferric nitrilotriacetate(Fe-NTA). Then, we have answered a question whether there are target genes in the oxidative stress-induced carcinogenesis by genetic analysis using F1 hybrid rats. This study revealed that chromosome 5 and 8 of rats showed a high incidence of loss of heterozygosity with PCR microsatellite analyses, which finally lead to a conclusion that p15/p16 tumor suppressor gene is one of the major target genes in this oxidative stress-induced carcinogenesis model.
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