| Project/Area Number |
15310036
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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 | Kanazawa University, Graduate School of Natural Science and Technology |
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Principal Investigator |
MATSUNAGA Tsukasa Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Professor, 自然科学研究科, 教授 (60192340)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGAKI Yasuhito Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Research Associate, 自然科学研究科, 助手 (20232275)
WAKASUGI Mitsuo Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Research Associate, 自然科学研究科, 助手 (80345595)
YAMASHITA Katsumi Kanazawa Univ., Grad.Sch.Nat.Sci.& Tech., Associate Professor, 自然科学研究科, 助教授 (10191280)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2004: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2003: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | DNA damage / nucleotide excision repair / ultraviolet light / cyclobutane pyrimidine dimer / (6-4) photoproduct / xeroderma pigmentosum / knock-out mouse / adaptive response / モノクローナル抗体 |
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| Research Abstract |
We have established a super-sensitive detection method for measuring cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs) induced by biological doses of ultraviolet (UV) light and suggested that human cells might have a novel repair system mainly for 6-4PPs other than nucleotide excision repair which has been thought to be only repair system for those lesions in humans so far. In this study, we have obtained the following findings.
1.The removal of 6-4PPs was observed even in the embryonic fibroblasts derived from xpa(-/-) or xpg(-/-) knock-out mice (30-50% after 24 hr). In addition, the removal of CPDs was also detected in those cells with a less efficiency (20-30% after 48 hr).
2.HeLa cells stably expressing AlwNI-type mutant XPA did not show any impairment of nucleotide excision repair activity, suggesting that this mutant XPA protein does not have a dominant-negative effect.
3.We have further sensitized the detection method for CPDs, enabling us to determine the repair kinetics of CPDs in cells exposed to non-killing doses of Was low as 0.1 J/m^2. Under this condition, we have found that xeroderma pimentosum cells significantly remove CPDs (〜40% after 48hr).
4.We could observe some weak enhancement of repair efficiency after UV irradiation of 1 J/m^2 when the human cells had been pie-exposed to 0.2 J/m^2. However, we need more extensive experiments to conclude whether the back-up repair system is under the control of adaptive responses.
Taken together with those results, we concluded that mammalian cells have a certain back-up repair system, independent of XPA and XPG, which removes mainly 6-4PP but also CPDs with a less efficiency.
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