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Analysis of DNA repair mechanism after heavy-ion irradiaiton and its application to radiation therapy

Research Project

Project/Area Number 15K10012
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Izumi Masako  国立研究開発法人理化学研究所, 仁科加速器科学研究センター, 専任研究員 (00280719)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords重粒子線 / DNA修復 / 放射線治療 / DNA二本鎖切断
Outline of Final Research Achievements

The heavy-ion irradiation is used as a radiation therapy, although DNA repair mechanism is not fully understood. In this research, the number of DNA double strand breaks or the foci of DNA repair proteins were analyzed after X-ray or heavy-ion irradiation with various linear energy transter in mammalian cells where specific DNA repair pathways were inhibited by the lack of DNA repair proteins genetically or the pretreatment of inhibitors against DNA repair proteins. The main repair pathway for DNA double strand breaks after both X-ray or heavy-ion irradiation was non-homologous end joining. In addition, homologous recombination could complement the defect of non-homologous end joining after X-ray irradaition, but not after high energy heavy-ion irradiation completely.

Academic Significance and Societal Importance of the Research Achievements

重粒子線は、X線に比べて高い致死効果を持つこと、標的部分のみに高い放射線量を与えることが可能であること、酸素効果の影響を受けにくいことから、先進的ながん治療法として利用されている。しかし、重粒子線に特異的なDNA損傷修復機構は完全に解明されていない。本研究は、重粒子線照射後のDNA損傷修復の理解に寄与するだけではなく、将来的には重粒子線照射とDNA修復阻害剤(抗がん剤)を組み合わせた新しい治療法の開発や、宇宙空間における有人飛行の放射線リスク評価に寄与することが期待できる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] The inhibitor of DNA-PK suppressed DNA repair after heavy-ion irradiation in quiescent mammalian cells.2019

    • Author(s)
      Izumi, M. and Abe, T.
    • Journal Title

      RIKEN Accel. Prog. Rep.

      Volume: 52

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recruitment of Rad51 and phosphorylated DNA-PKcs after heavy-ion irradiation of human normal fibroblast.2018

    • Author(s)
      Izumi, M. and Abe, T
    • Journal Title

      RIKEN Accel. Prog. Rep.

      Volume: 51

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Mcm2-7-interacting domain of human mini-chromosome maintenance 10 (Mcm10) protein is important for stable chromatin association and origin firing.2017

    • Author(s)
      Izumi, M., Mizuno, T., Yanagi, K., Sugimura, K., Okumura, K., Imamoto, N., Abe, T., and Hanaoka, F.
    • Journal Title

      J. Biol. Chem.

      Volume: 292 Pages: 13008-13021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction.2017

    • Author(s)
      Amino M, Yoshioka K, Furusawa Y, Tanaka S, Kawabe N, Hashida T, Tsukada T, Izumi M, Inokuchi S, Tanabe T, Ikari Y
    • Journal Title

      Pacing and Clinical Electrophysiology

      Volume: 40 Issue: 4 Pages: 379-390

    • DOI

      10.1111/pace.13031

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The focus formation of Rad51 and phosphorylated DNA-PK after heavy-ion irradiation in mammalian cells.2017

    • Author(s)
      Izumi, M. and Abe, T.
    • Journal Title

      RIKEN accel. Prog. Rep.

      Volume: 50

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The defect of non-homologous end joining substantially enhanced the focus formation of Rad51 after X-ray irradiation, but not after heavy-ion irradiation.2016

    • Author(s)
      Izumi, M. and Abe, T.
    • Journal Title

      RIKEN Accel. Prog. Rep

      Volume: 49

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localization of Rad51 and phosphorylated DNA-PKsc after heavy-ion irradiation in mammalian cells2015

    • Author(s)
      Izumi, M. and Abe, T.
    • Journal Title

      RIKEN Accel. Prog. Rep

      Volume: 48 Pages: 301-301

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Bystander cell killing effects induced by low-fluences of high-LET radiations2018

    • Author(s)
      Tomita, M., Tsukada, T., and Izumi, M.
    • Organizer
      the 64th Annual Radiation Research Society Meeting
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトMcm10のMcm2-7相互作用ドメインの同定2017

    • Author(s)
      泉 雅子、水野 武、柳 憲一郎、杉村和人、奥村克純、今本尚子、阿部知子、花岡文雄
    • Organizer
      第24回DNA複製・組換え・修復ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] Low-dose high-LET heavy ion-induced bystander cell killing effect2015

    • Author(s)
      Tomita, T., Tsukada, T., and Izumi, M.
    • Organizer
      The 61st Annual Meeting of the Radiation Research Society
    • Place of Presentation
      Florida, USA
    • Year and Date
      2015-09-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Effects of Radiation on Human Body (DVD)2015

    • Author(s)
      Izumi, M.
    • Publisher
      Japan Radioisotope Association
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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