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Study of biological effects of ionizing radiation on mitochondria

Research Project

Project/Area Number 18H03377
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 63020:Radiation influence-related
Research InstitutionNational Institute of Public Health

Principal Investigator

Shimura Tsutomu  国立保健医療科学院, その他部局等, 上席主任研究官 (40463799)

Co-Investigator(Kenkyū-buntansha) 笹谷 めぐみ (豊島めぐみ)  広島大学, 原爆放射線医科学研究所, 准教授 (80423052)
稲葉 洋平  国立保健医療科学院, その他部局等, 上席主任研究官 (80446583)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Keywords放射線発がん / ミトコンドリア / 活性酸素 / がんの微小環境 / 酸化ストレス / がん微小環境 / 低線量放射線 / 発がん / 微小環境
Outline of Final Research Achievements

Tumor stromal cells have an important role on tumor initiation and development. We here analyzed the role of human fibroblasts on radiation-related tumors. We revealed that radiation-induced mitochondrial reactive oxygen sepsis (ROS) activated fibroblasts to form tumor microenvironment. Furthermore, radiation prevented removal of mitochondrial ROS by inactivating glutathione peroxidase (GPx), leading to induction of oxidative stresses in the irradiated cells. Our findings will provide new insights in the mechanisms of oxidative stress associated with radiation-related tumor.

Academic Significance and Societal Importance of the Research Achievements

本研究は、放射線発がんの発症機構の解明を目的としている。低線量放射線の健康影響の科学的解明は学術的に重要であるのみならず、福島事故で懸念されている健康影響評価においても必要である。さらに、得られた研究成果は、放射線リスク評価の科学的根拠として放射線に不安を持つ人々への対策に活用する。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (15 results)

All 2022 2021 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Biological effects of tritium and the issue of radiation effects at low-doses2021

    • Author(s)
      志村 勉、山口 一郎、寺田 宙、温泉川 肇彦、牛山 明
    • Journal Title

      Journal of the National Institute of Public Health

      Volume: 70 Issue: 2 Pages: 160-165

    • DOI

      10.20683/jniph.70.2_160

    • NAID

      130008057047

    • ISSN
      1347-6459, 2432-0722
    • Year and Date
      2021-05-31
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts2021

    • Author(s)
      Shimura Tsutomu、Nakashiro Chinami、Fujiwara Kazusi、Shiga Rina、Sasatani Megumi、Kamiya Kenji、Ushiyama Akira
    • Journal Title

      Journal of Radiation Research

      Volume: 63 Issue: 2 Pages: 183-191

    • DOI

      10.1093/jrr/rrab122

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATM-Mediated Mitochondrial Radiation Responses of Human Fibroblasts2021

    • Author(s)
      Shimura Tsutomu
    • Journal Title

      Genes

      Volume: 12 Issue: 7 Pages: 1015-1015

    • DOI

      10.3390/genes12071015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of mitochondrial oxidative stress and the tumor microenvironment in radiation-related cancer2021

    • Author(s)
      Shimura Tsutomu
    • Journal Title

      Journal of Radiation Research

      Volume: 62 Issue: Supplement_1 Pages: i36-i43

    • DOI

      10.1093/jrr/rraa090

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epicatechin as a Promising Agent to Countermeasure Radiation Exposure by Mitigating Mitochondrial Damage in Human Fibroblasts and Mouse Hematopoietic Cells2019

    • Author(s)
      1) Tsutomu Shimura, Mao Koyama, Daiki Aono, Naoki Kunugita
    • Journal Title

      The FASEB J

      Volume: in press Issue: 6 Pages: 6867-6876

    • DOI

      10.1096/fj.201802246rr

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fukushima Nuclear Disaster: Emergency Response to the Disaster2019

    • Author(s)
      Shimura Tsutomu、Yamaguchi Ichiro、Kunugita Naoki
    • Journal Title

      Encyclopedia of Environmental Health, 2nd Edition.

      Volume: - Pages: 96-106

    • DOI

      10.1016/b978-0-12-409548-9.10974-1

    • ISBN
      9780444639523
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells2018

    • Author(s)
      Kunoh T, Shimura T, Kasai T, Matsumoto S, Mahmud H, Khayrani A, Seno M, Kunoh H, Takada J.
    • Journal Title

      Nanotechnology

      Volume: 30 Issue: 5 Pages: 055101-055101

    • DOI

      10.1088/1361-6528/aaedd5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiation-Induced Myofibroblasts Promote Tumor Growth via Mitochondrial ROS-Activated TGFβ Signaling.2018

    • Author(s)
      Shimura T, Sasatani M, Kawai H, Kamiya K, Kobayashi J, Komatsu K, Kunugita N
    • Journal Title

      Mol. Cancer Res.

      Volume: 16(11) Issue: 11 Pages: 1676-1686

    • DOI

      10.1158/1541-7786.mcr-18-0321

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Mitochondrial damage as a biological marker for dose assessment2022

    • Author(s)
      Shimura T, Ushiyama A
    • Organizer
      EPR BioDose 2022
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of tumor microenvironment formation in radiation-induced tumor.2021

    • Author(s)
      Shimura T, Ushiyama A
    • Organizer
      Procedings of the 30th Anniversary International Symposium on the “Environmental Dynamics of Radionuclides and the Biological Effects of Low Dose-rate Radiation.”
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Radiation-induced inactivation of glutathione peroxidase activity in human fibroblasts for disruption of glutathione redox homeostasis2021

    • Author(s)
      Shimura T, Nakashiro C,Fujiwara K, Shiga R, Ushiyama A
    • Organizer
      日本放射線影響学会第64回
    • Related Report
      2020 Annual Research Report
  • [Presentation] 放射線被ばく線量評価の新たな指標としてのミトコンドリア損傷の検討2021

    • Author(s)
      志村勉,牛山明
    • Organizer
      第58回全国衛生化学技術協議会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells.2019

    • Author(s)
      Shimura T , Koyama M, Aono D, Kunugita N
    • Organizer
      日本放射線影響学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 放射線誘発がん関連線維芽細胞は、活性酸素によるTGFbeta;シグナリング経路の活性化を介してがんの増殖を促進する2018

    • Author(s)
      志村勉、笹谷めぐみ、河合秀彦、神谷研二、小林純也、小松賢志、欅田尚樹
    • Organizer
      第61回日本放射線影響学会
    • Related Report
      2018 Annual Research Report
  • [Book] Encyclopedia of Environmental Health, 2nd Edition.2019

    • Author(s)
      Shimura T, Yamaguchi I. Kunugita N
    • Total Pages
      4884
    • Publisher
      ELSEVIER
    • ISBN
      9780444639516
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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