Molecular and cellular analyses of hematopoietic stem cell damage induced by low dose-rate irradiation
| Project/Area Number |
16H02955
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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 and chemicals
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大野 芳典 広島大学, 原爆放射線医科学研究所, 助教 (10548986)
安永 晋一郎 福岡大学, 医学部, 教授 (50336111)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 低線量放射線被ばく / 造血幹細胞 / 長期骨髄再構築能 / 多分化能 / 低線量率放射線被ばく / 低線量被ばく |
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| Outline of Final Research Achievements |
Hematopoietic tissues are highly sensitive to radiation and prone to radiation injury. It is feared that hematopoietic failure develops and, as a result of the later effects, hematopoietic abnormalities such as leukemia could be induced. We have analyzed effects of low dose-rate radiation exposure on hematopoietic tissues, that have largely remained elusive, and aimed to contribute for establishing a basic theory for preventing the adverse effects of low dose-rate exposure. We found that low dose-rate radiation exposure specifically decreased the number and activity of immature hematopoietic cells including hematopoietic stem cells. We then detailed the mechanism underlying the decrease at the molecular and cellular levels, further at the single cell level. Not only DNA repair responses against the genome damage but also apoptosis and cellular differentiation were induced in immature hematopoietic cells, which may give rise to specific reduction of immature hematopoietic cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、今まで充分には明らかにされて来なかった低線量率放射線被ばくの造血システムへの影響について細胞レベルから分子レベルまで詳細に解析した。原発作業や宇宙開発などの環境下では、長期間に渡る低線量率放射線被ばくが生ずることが危惧され、本研究で明らかにしたように造血幹細胞の特異的な減少や機能障害によって造血不全や免疫不全が引き起こされる危険性が考えられる。本研究成果を基に、低線量率放射線被ばくによって造血幹細胞障害が引き起こされるメカニズムが更に明らかにされ、新たな防御法の開発に道が開かれることを期待したい。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] BMI1 controls transit amplification in chondrogenesis by preventing replication and transcription fork collision.2019
Author(s)
Spaapen F, Eijssen L, Welting T, Prickaerts P, Salvaing J, Dahlmans V, Surtel D A M, Kruitz F, Kuijer R, Takihara Y, Wouters B G, Vidal M, Voncken J.W.
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Journal Title
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A revised map for the commitment of human CD34-negative hematopoietic stem cells.2018
Author(s)
Sumide, K., Matsuoka, Y., Kawamura, H., Nakatsuka, T., Fujioka, T., Asano, H., Takihara, Y., Sonoda, Y.
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Journal Title
Nature Communications
Volume: 印刷中
Related Report
Peer Reviewed / Open Access
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[Journal Article] PRC1 prevents replication stress during chondrogenic transit amplification2017
Author(s)
Spaapen, F., Eijssen, L.M., Adriaens, M.E., Welting, T.J., Prickaerts, P., Salvaing, J., Dahlmans, V.E.H., Surtel, D.A.M., Kruitz, F., Kuijer, R., Takihara, Y., Marks, H., Stunnenberg, H.G., Wouters, B.G., Vidal, M., Voncken, J.W.
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Journal Title
Epigenomes
Volume: 1(3)
Issue: 3
Pages: 22-22
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Effect of low dose-rate irradiation on the hematopoietic stem cells2017
Author(s)
Ohno, Y., Shirasu, N., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Takihara, Y.
Organizer
The 1st International Symposium of the network-type Joint Usage/ Research Center for Radiation Disaster Medical Science
Place of Presentation
Hiroshima, Japan
Year and Date
2017-02-21
Related Report
Int'l Joint Research
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[Presentation] Low dose-rate irradiation specifically affects hematopoietic stem cells.2016
Author(s)
Ohno, Y., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Naka, K., Takihara, Y.
Organizer
第78回日本血液学会学術集会
Place of Presentation
横浜
Year and Date
2016-10-13
Related Report
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[Presentation] Low dose-rate irradiation specifically affects hematopoietic stem cells2016
Author(s)
Takihara, Y., Ohno, Y., Suzuki-Takedachi, K., Santo M., Yasunaga, S., Ohtsubo, M., Naka, K.
Organizer
45th Annual Scientific Meeting of the International Society of Experimental Hematology
Place of Presentation
San Diego, USA
Year and Date
2016-08-25
Related Report
Int'l Joint Research
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[Presentation] Effect of low dose-rate irradiation on the hematopoietic system.2016
Author(s)
Ohno, Y., Suzuki-Takedachi, K., Santo, M., Guo, Y., Kanno, M., Yasunaga, S., Ohtsubo, M., Naka, K., Takihara, Y.
Organizer
The 14th Stem Cell Research Symposium
Place of Presentation
Awaji, Japan
Year and Date
2016-05-20
Related Report
