| Project/Area Number |
15310037
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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 | Kyoto University |
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Principal Investigator |
YONEI Shuji Kyoto University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (60093340)
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| Co-Investigator(Kenkyū-buntansha) |
ZHANG Qiu-mei Kyoto University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (00260604)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Ionizing radiation / Oxidative stress response / DNA repair / Base excision repair / DNA glycosylase / Regulation of gene expression / Oxidative base damage / Clustered DNA damage / 放射線感受性 / 活性酸素 / APエンドヌクレアーゼ / 8-オキソグアニン / ストレス応答 / 過剰発現 / 放射線 / 塩基損傷 / 二重鎖切断 / 修復 / 致死作用 |
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| Research Abstract |
(1)It is well-known that ionizing radiation such as X-rays, gamma-rays and alpha-particles, produces a unique form of DNA damage called "clustered damage", which contains two or more lesions induced within the one or two helical turns of DNA. Many of the lesions induced by ionizing radiation are chemically indistinguishable from those induced by reactive oxygen species produced as by-products of oxidative metabolism. However, clustered damage induced by ionizing radiation would be less readily repaired than isolated lesions. Therefore clustered damage might be biologically significant. In this report we showed that HeLaS3 cells overexpressing hOGG1 in nucleus or mitochondria were more sensitive to gamma-rays than HeLaS3 cells. We have determined the level of chromosomal double strand breaks by gamma-H2AX foci formation, clustered damages produced by ionizing radiation might be converted to lethal double-strand breaks during attempted base excision repair. Our results that overexpressio
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n of hOGG1 in mitochondria protein enhanced the sensitivity to gamma-rays suggest that double-strand breaks are also induced by abortive base excision repair in mitochondrial genome. (2)Ionizing radiation and reactive oxygen species produce various types of oxidative damage to DNA, which cause mutations in cells. Bacteria and eukaryotes have DNA repair systems to prevent mutations. Oxidative base damages are principally repaired by base excision repair (BER) mechanisms. However, there are no indications that oxidative damages are directly reversed on the DNA strand. In this study, we examined whether oxidative damages are directly reversed on the DNA strand. We used pUB3 plasmid irradiated with gamma-rays and tsubsequently treated with a reducing agent, dithiolthreitol (DTT). E.coli cells were transformed with the pUB3. As a result, the transformation efficiency of pUB3 treated with DTT was higher than that of pUB3 without DTT treatment. We are currently investigating the mutation spectra of the pUB3. Less
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