Role of non-homologous end joining in biological response under low dose-rate irradiation condition
Project/Area Number |
24310045
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Risk sciences of radiation/Chemicals
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Research Institution | Central Research Institute of Electric Power Industry |
Principal Investigator |
Tomita Masanori 一般財団法人電力中央研究所, 原子力技術研究所, 上席研究員 (00360595)
|
Co-Investigator(Renkei-kenkyūsha) |
OTSUKA Kensuke 一般財団法人電力中央研究所, 原子力技術研究所, 主任研究員 (50371703)
KOBAYASHI Junya 京都大学, 放射線生物研究センター, 准教授 (30301302)
|
Project Period (FY) |
2012-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
|
Keywords | 放射線 / 細胞・組織 / シグナル伝達 / 幹細胞 / DNA損傷 |
Outline of Final Research Achievements |
Radiation-induced biological effects are mainly caused by an accumulation of unrepaired DNA double-strand breaks (DSBs). DNA Ligase IV (Lig4) is one of the key protein of non-homologous end-joining (NHEJ), which is a major DSB repair pathway in mammalian cells. In this study, we found that the Lig4 mutated mice irradiated with low dose-rate γ-rays at 1 mGy/h died earlier than those irradiated with 1 Gy of X-rays at high dose-rate (0.5 Gy/min). We clarified that early exhaustion of hematopoietic stem cells due to accumulation of DNA damage and then acceleration of stem cell turnover was occurred in the Lig4 mutated mice under low dose-rate irradiation conditions as a cause of this. Our obtained results suggest that NHEJ is a chief DSB repair mechanism in maintaining the integrity of the genome under low dose-rate irradiation conditions.
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Report
(6 results)
Research Products
(13 results)