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Studies on defensive cellular response by nucleus and cytoplasm targeted irradiation using microbeam

Research Project

Project/Area Number 16K15586
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Konishi Teruaki  国立研究開発法人量子科学技術研究開発機構, 放射線障害治療研究部, 主任研究員(定常) (70443067)

Research Collaborator KOBAYASHI Alisa  
OHSAWA Daisuke  
OIKAWA Masakazu  
FURUSAWA Yoshiya  
WANG Jun  
AUTSAVAPROMPORN Narongchai  
Tengku Ahmad Tengku Ahbrizal Farizal  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsマイクロビーム / 細胞質 / ミトコンドリア / 酸化ストレス応答 / NRF2 / DNA修復 / Mito-Sox / 放射線治療生物学 / DNA二本鎖切断修復 / スーパーオキサイド / DNA二本鎖切断 / γ-H2AX / 陽子線 / g-H2AX / Nrf2 / 放射線 / 細胞・組織 / 生物物理 / 量子ビーム / シグナル伝達
Outline of Final Research Achievements

Our aim was to clarify the radiation induced cytoplasmic damage and its cellular response. Taking advantage of the advanced technology of SPICE-NIRS microbeam, we were able to precisely target the nucleus and cytoplasm. Experimentally, human lung normal cells were microbeam targeted in the nucleus, cytoplasm, or both to investigate the site-specific cellular response. As result, cytoplasmic irradiation induced DNA double strand breaks as a result of cellular response of mitochondria damage and not because of direct energy deposition by the proton beam. In addition, we found that activation of NRF2, a transcriptional factor of anti-oxidative response gene, and upregulation of responsible target genes. Altogether, we demonstrated that cytoplasmic damage triggers defensive cellular response against radiation, that were followed by activation oxidative response pathway and also DSB repair pathway.

Academic Significance and Societal Importance of the Research Achievements

本課題では、放射線によって誘発される細胞質損傷を起因とする細胞応答は、DNA損傷の修復過程を促進するという結果を報告した。放射線による生物効果の第一ターゲットはDNAであるとした古典的な放射線生物学に対して、本研究では、第二ターゲットとして細胞質が存在し、それは放射線に対して防御的に働くことを示したことは学術的に重要であり、放射線以外の基礎生物学分野においても発展性が大きいと考える。そして、細胞の放射線感受性を左右するであろう細胞質損傷応答およびその経路は、放射線リスク推定とモデル化、並びに放射線がん治療においても、重要なファクターになり得ることからその社会的な意義は大きいと考える。

Report

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

    (23 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (9 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Int'l Joint Research] Chinese Academy of Sciences(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Malaysia Nuclear Agency(マレーシア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Chiang Mai University(タイ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Hefei Institute of Physical Science, CAS/Institute of Modern Physics, CAS/Department of Physics, Peking University(中国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Malaysian Nuclear Agency(マレーシア)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Chiang Mai University(タイ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Chinese Academy of Sciences(中国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Malaysian Nuclear Agency(マレーシア)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Chiang Mai University(タイ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Nuclear factor (erythroid‐derived 2)‐like 2 antioxidative response mitigates cytoplasmic radiation‐induced DNA double‐strand breaks2019

    • Author(s)
      Jun Wang、Teruaki Konishi
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 2 Pages: 686-696

    • DOI

      10.1111/cas.13916

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of SPICE microbeam size using fluorescent nuclear track detector (FNTD)2019

    • Author(s)
      Daisuke Ohsawa, Yoshiya Furusawa, Alisa Kobyashi, Masakazu Oikawa, Teruaki Konishi
    • Journal Title

      Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced DNA double strand break repair triggered by microbeam irradiation induced cytoplasmic damage2018

    • Author(s)
      Teruaki Konishi , Alisa Kobayashi, Tengku Ahbrizal Farizal Tengku Ahmad, Jun Wang
    • Journal Title

      Journal of Radiation and Cancer Research

      Volume: 9 Issue: 4 Pages: 183-183

    • DOI

      10.4103/jrcr.jrcr_21_18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SPICE-NIRSマイクロビームが先導する放射線生物学(Single Cell Radio-Biology)2018

    • Author(s)
      小西 輝昭, 小林 亜利紗, 大澤 大輔, 及川 将一, Narongchai Autsavapromporn, Tengku Ahmad Fabrizal Tengku Ahmad, Jun Wang
    • Organizer
      量子生命科学研究会第2回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SPICE-NIRSマイクロビームが先導する放射線生物学・医科学研究2018

    • Author(s)
      小西 輝昭
    • Organizer
      ビーム物理研究会(若手の会)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] FNTDを用いたSPICEマイクロビームサイズの高精度評価方法の開発2018

    • Author(s)
      大澤 大輔, 古澤 佳也, 小林 亜利紗, 及川 将一, 小西 輝昭
    • Organizer
      量子生命科学研究会第2回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Study on cytoplasmic radiation induced defensive signaling using NIRS-SPICE microbeam2018

    • Author(s)
      Jun Wang, Teruaki Konishi, Alisa Kobayashi, Yoshiya Furusawa, Masakazu Oikawa, Daisuke Ohsawa, Narongchai Autsavapromporn, Tengku Ahbrizal Farizal Tengku Ahmad
    • Organizer
      量子生命科学研究会第2回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 蛍光飛跡検出器(Al2O3: C, Mg)を用いたSPICEマイクロビームサイズの高精度評価2018

    • Author(s)
      大澤 大輔, 古澤 佳也, 小林 亜利紗, 及川 将一, 小西 輝昭
    • Organizer
      量子生命科学研究会 第2回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SPICE-NIRSマイクロビームが先導する放射線生物学・医科学研究2018

    • Author(s)
      大澤 大輔, 古澤 佳也, 小林 亜利紗, 及川 将一, 小西 輝昭
    • Organizer
      量子生命科学研究会 第2回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of SPICE microbeam profile using fluorescent nuclear track detector (FNTD)2018

    • Author(s)
      Daisuke Ohsawa, Yoshiya Furusawa, Alisa Kobayashi, Masakazu Oikawa, Teruaki Konishi
    • Organizer
      16th International conference on nuclear microscope technology and applications
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SPICE-NIRS microbeam:マイクロビームのアドバンテージを活用した放射線生物研究2017

    • Author(s)
      小西 輝昭, 小林 亜利紗, 大澤 大輔, 劉 翠華, 古澤 佳也, 及川 将一
    • Organizer
      日本放射線影響学会第60回大会, 日本放射線影響学会
    • Related Report
      2017 Research-status Report
  • [Presentation] SPICE-NIRS microbeam: A focused vertical system for proton irradiation of a single cell for radiobiological research.2017

    • Author(s)
      Teruaki Konishi, Masakazu Oikawa, Alisa Kobayashi, Daisuke Ohsawa, Shino Homma-Takeda, Yoshiya Furusawa, Tsuyoshi Hamano
    • Organizer
      1st QST International Symposium "Quantum Life Science" -The pathbreaking life-scientists with quantum eyes and hands-, National Institutes for Quantum and Radiological Science and Technology (QST)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] SPICE-NIRS microbeam: Current developments and radiobiological studies2017

    • Author(s)
      Teruaki Konishi
    • Organizer
      15th Chinese Biophysics Congress, Biophysical Society of China
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Microbeam induced cytoplasmic damage triggers activation of DNA double-stran d break repair2016

    • Author(s)
      小西 輝昭, 小林 亜利紗, 古澤 佳也, 劉 翠華, 及川 将一, Tengku Ahbrizal Farizal Tengku Ahmad, Narongchai Autsavapromporn, Jun Wang
    • Organizer
      日本放射線影響学会第59回大会, 日本放射線影響学会
    • Place of Presentation
      広島市、JMSアステールプラザ
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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