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

• Project/Area Number: 15K10012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Institute 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: ¥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。

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Localization of Rad51 and phosphorylated DNA-PKsc after heavy-ion irradiation in mammalian cells (2015)
  • Author(s): Izumi, M. and Abe, T.
  • Journal Title: RIKEN Accel. Prog. Rep Volume: 48 Pages: 301-301
  • Peer Reviewed / Open Access
• [Presentation] Bystander cell killing effects induced by low-fluences of high-LET radiations (2018)
  • Author(s): Tomita, M., Tsukada, T., and Izumi, M.
  • Organizer: the 64th Annual Radiation Research Society Meeting
  • 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
• [Presentation] Low-dose high-LET heavy ion-induced bystander cell killing effect (2015)
  • 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
  • Int'l Joint Research
• [Book] Effects of Radiation on Human Body (DVD) (2015)
  • Author(s): Izumi, M.
  • Publisher: Japan Radioisotope Association