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Analyzing the mechanism of radiation carcinogenesis by identifying the earliest driver mutations

Research Project

Project/Area Number 21K12250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 63020:Radiation influence-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

IIZUKA Daisuke  国立研究開発法人量子科学技術研究開発機構, 放射線医学研究所 放射線影響研究部, グループリーダー (00455388)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords放射線誘発乳がん / 細胞系譜追跡 / 遺伝子変異 / 乳腺幹細胞 / ゲノム異常 / ゲノム変異解析 / 放射線発がん
Outline of Research at the Start

低線量被ばくでは、発がんのリスク評価が最重要課題である。本研究では、薬剤投与によりマウス体内で幹細胞とその子孫細胞を標識できる細胞系譜追跡技術を駆使し、がんの最初期の“芽”であるクローン性増殖を捉え、それをゲノム解析することにより、放射線誘発がん最初期の遺伝子変異を同定することを目的としている。

Outline of Final Research Achievements

It is well established that radiation exposure increases the risk of cancer. However, the details of the underlying mechanism remain unclear. In this study, we aim to elucidate the mechanism of radiation carcinogenesis by conducting cell lineage tracing experiments that can capture the dynamics of irradiated cells and the formation of cancer, capturing clones derived from single cells, and analyzing their genetic mutations. A system has been established to capture clones of mammary cells obtained after radiation exposure, extract DNA from them, and perform PCR analysis. While the initial stage of radiation carcinogenesis has not yet been identified in terms of genetic mutations, it is believed that this will be possible in the future.

Academic Significance and Societal Importance of the Research Achievements

広島・長崎の原爆被爆や、福島原発事故を経験した日本において、特に子供の放射線被ばくによる発がんが大きな不安材料の一つとして残されている。これは、放射線発がんメカニズムが明らかになっていないことが原因である。そのため、そのメカニズムの詳細を明らかにする必要がある。本研究では、マウス体内で被ばくした細胞のその後の運命を観察できる細胞系譜追跡により、単一細胞由来のクローンを捉え、その遺伝子変異解析により、放射線発がんの最初期に起こる遺伝子変異を捉えることができる実験系を確立することができた。こ本研究が進展することで、エビデンスに基づく放射線被ばくリスクの理解が進むことが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

All Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Presentation] Characteristic cellular dynamics in mammary gland after radiation exposure; Toward elucidation of radiation-induced mammary cancer mechanisms.2023

    • Author(s)
      Daisuke Iizuka, Mari Ogawa, Mayumi Shinagawa, Chizuru Tsuruoka, Masaaki Sunaoshi, Tatsuhiko Imaoka, Shizuko Kakinuma.
    • Organizer
      17th International Congress for Radiation Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Radiation-induced mammary cancer mechanism from the viewpoint of cellular dynamics.2023

    • Author(s)
      Daisuke Iizuka, Mari Ogawa, Mayumi Shinagawa, Chizuru Tsuruoka, Masaaki Sunaoshi, Shizuko Kakinuma, Tatsuhiko Imaoka
    • Organizer
      ICRP2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characteristic cell dynamics in mammary tissue after radiation exposure as revealed by cell lineage tracing experiments.2022

    • Author(s)
      Daisuke Iizuka, Chizuru Tsuruoka, Tatsuhiko Imaoka, Shizuko Kakinuma.
    • Organizer
      第81回日本癌学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mechanism of suppression of mammary cell clonal expansion by radiation exposure: possible involvement of cellular senescence.2022

    • Author(s)
      Daisuke Iizuka, Mayumi Shinagawa, Mari Ogawa, Chizuru Tsuruoka, Masaaki Sunaoshi, Tatsuhiko Imaoka, Shizuko Kakinuma.
    • Organizer
      第19回幹細胞シンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] 細胞系譜追跡実験で明らかになった低線量被ばく後の乳腺組織における特徴的な細胞動態2022

    • Author(s)
      飯塚大輔
    • Organizer
      第8回低線量放射線研究交流会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Biological effect of radiation exposure on clonal proliferation of mammary stem cells using a lineage tracing technology.2021

    • Author(s)
      Daisuke Iizuka, Chizuru Tsuruoka, Mayumi Shinagawa, Masaaki Sunaoshi, Tatsuhiko Imaoka, Shizuko Kakinuma.
    • Organizer
      第18回幹細胞シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Biological effects of radiation exposure on mammary cell clonal expansion revealed by cell lineage tracing experiments.2021

    • Author(s)
      Daisuke Iizuka, Chizuru Tsuruoka, Tatsuhiko Imaoka, Shizuko Kakinuma.
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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