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Basic research on the radiation response of small molecule organic compounds at low concentrations by low dose X-ray irradiation

Research Project

Project/Area Number 19K22609
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionWaseda University (2021)
National Institute of Advanced Industrial Science and Technology (2019-2020)

Principal Investigator

Takahashi Junko  早稲田大学, 理工学術院(情報生産システム研究科・センター), 教授(任期付) (80415702)

Co-Investigator(Kenkyū-buntansha) 岩橋 均  岐阜大学, 応用生物科学部, 教授 (60356540)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords放射線増感 / 放射線応答 / 有機化合物 / プロトポルフィリン / 活性酸素 / スパーオキシド / OHラジカル / ジヒドロエチジウム(DHE) / スーパーオキシド / ジヒドロエチジウム(DHE) / 放射線治療 / 放射線増感剤
Outline of Research at the Start

低分子有機化合物の放射線応答性に関する詳細なデータを蓄積、体系化して、放射線応答性の理解を深める。これにより、これまで着目されなかった低濃度、低線量における低分子有機化合物の放射線応答を利用した放射線増感剤の可能性を示す。将来的には、現在の放射線治療効果を凌駕する放射線力学療法の開発につなげる。

Outline of Final Research Achievements

Protoporphyrin IX (PpIX), which selectively accumulates in cancer cells by administration of 5-aminolevulinic acid, enhances the production of reactive oxygen species (ROS) by X-ray irradiation and functions as a radiosensitizer in radiotherapy.
The purpose of this study is to investigate the X-ray responsiveness of small molecule organic compounds other than PpIX. We verified the integrity of our methodology using ROS detection probe reactions in X-ray irradiation. We investigated the X-ray responsiveness and cytotoxicity of sensitizer candidate substances. In addition, we evaluate DNA strand break properties of PpIX by X-ray irradiation. As a result, various kinds of small molecule organic compounds show X-ray responsiveness and radiosensitizing effect. Evaluation using derivatives also suggested that the radiation responsiveness of organic compounds is related to the molecular structure.

Academic Significance and Societal Importance of the Research Achievements

PpIXは分子量563の低分子有機化合物であり、放射線吸収の小さい有機化合物の存在により、放射線の活性酸素生成能が増強されること、またその物理化学的な反応メカニズムに関しては、これまでにほとんど知られていない。低分子有機化合物の放射線応答性に関する詳細なデータを蓄積し、それを体系化して、放射線応答性の理解を深めることは、これまで着目されなかった低濃度、低線量における低分子有機化合物の応答に関する新規の学術分野の開拓につながる。いかなる高精度な放射線治療装置でも細胞レベルでの照射は困難であり、がん細胞選択性を有する放射線増感剤の開発は現在の放射線治療を凌駕する新規放射線治療法の実用化につながる。

Report

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

    (13 results)

All 2021 2020 2019

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (4 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy2021

    • Author(s)
      Takahashi Junko、Nagasawa Shinsuke、Doi Motomichi、Takahashi Masamichi、Narita Yoshitaka、Yamamoto Junkoh、Ikemoto Mitsushi J.、Iwahashi Hitoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 9762-9762

    • DOI

      10.3390/ijms22189762

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Why Concurrent CDDP and Radiotherapy Has Synergistic Antitumor Effects: A Review of In Vitro Experimental and Clinical-Based Studies2021

    • Author(s)
      Nagasawa Shinsuke、Takahashi Junko、Suzuki Gen、Hideya Yamazaki、Yamada Kei
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 6 Pages: 3140-3140

    • DOI

      10.3390/ijms22063140

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 新たな放射線治療法開発の取り組み:放射線力学療法(Radiodynamic Therapy)2021

    • Author(s)
      高橋淳子
    • Journal Title

      光アライアンス

      Volume: 1 Pages: 7-11

    • Related Report
      2020 Research-status Report
  • [Journal Article] Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review2020

    • Author(s)
      Takahashi Junko、Nagasawa Shinsuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 23 Pages: 9324-9324

    • DOI

      10.3390/ijms21239324

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma2020

    • Author(s)
      Hasegawa Takema、Takahashi Junko、Nagasawa Shinsuke、Doi Motomichi、Moriyama Akihiro、Iwahashi Hitoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 7 Pages: 2302-2302

    • DOI

      10.3390/ijms21072302

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening of X-ray responsive substances for the next generation of radiosensitizers2019

    • Author(s)
      Moriyama Akihiro、Hasegawa Takema、Jiang Lei、Iwahashi Hitoshi、Mori Takashi、Takahashi Junko
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-019-54649-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bayesian inference for three-dimensional helical reconstruction using soft-body model.2019

    • Author(s)
      3.M.Ohashi, S.Maeda, C.Sato
    • Journal Title

      Physical Review E

      Volume: 100 Issue: 20 Pages: 1-9

    • DOI

      10.3390/ijms20205155

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between flavonoid structure and reactive oxygen species generation upon ultraviolet and X-ray irradiation2019

    • Author(s)
      Jiang Lei、Yanase Emiko、Mori Takashi、Kurata Kanae、Toyama Michiru、Tsuchiya Ayaka、Yamauchi Kosei、Mitsunaga Tohru、Iwahashi Hitoshi、Takahashi Junko
    • Journal Title

      Journal of Photochemistry and Photobiology A: Chemistry

      Volume: 384 Pages: 112044-112044

    • DOI

      10.1016/j.jphotochem.2019.112044

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 5-アミノレブリン酸を用いる放射線力学療法(Radiodynamic Therapy)の可能性2020

    • Author(s)
      高橋淳子
    • Organizer
      第41回 日本レーザー医学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 黒色腫脳転移モデルマウスを用いた5-ALA放射線力学療法の検証2020

    • Author(s)
      高橋 淳子, 長澤 慎介
    • Organizer
      日本放射線腫瘍学会第33回学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 新たな放射線治療法開発の取り組みー放射線力学療法(Radiodynamic Therapy)2019

    • Author(s)
      高橋淳子
    • Organizer
      第40回レーザー医学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 放射線治療用増感剤開発のためのX線反応性物質の大規模スクリーニング2019

    • Author(s)
      高橋淳子、他
    • Organizer
      日本放射線影響学会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 放射線増感剤2019

    • Inventor(s)
      Junko Takahashi et al,
    • Industrial Property Rights Holder
      Junko Takahashi et al,
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas

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Published: 2019-07-04   Modified: 2023-01-30  

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