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Study of genomic instability risk arisen by UV and ionizing radiation

Research Project

Project/Area Number 21K12252
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 Cancer Center Japan

Principal Investigator

Yoshioka Ken-ichi  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (70321916)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsゲノム不安定性 / 放射線 / 紫外線 / DNA損傷 / 発がん / 複製ストレス / エピゲノム / UV / がん
Outline of Research at the Start

放射線やUVへのばく露は、がんのリスク要因である。直接の影響はDNA損傷と考えられるが、『放射線およびUVで生じた“どのタイプの損傷”がどの様にがん化を促進しているのか』、未だに不明な点が多い。一方で、がん化の進行過程では、ゲノム不安定性誘導に起因して、変異が誘導され、防御機構の破綻した細胞のクローン進化に至ることが明確になってきた。そこで、本研究では、放射線やUVへのばく露によるゲノム不安定性へのリスク影響を解析する。

Outline of Final Research Achievements

Ultra Violet (UV) light, primarily inducing cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PPs), risks skin cancer with genomic instability. However, it is still unclear how the photoproducts are associated with genomic instability. Similarly, ionizing radiation could also cause multiple types of DNA damages, it is not clear which of those are responsible. Here we studied that replication stress-associated DNA double strand breaks (DSBs) risking genomic instability are those mechanistic backgrounds. We observed that both UV and ionizing radiation are associated with DNA replication stress and hence risking genomic instability. Resulting cells are subjected to the clonal evolution of cells mutated in the ARF/p53 pathway.

Academic Significance and Societal Importance of the Research Achievements

放射線や紫外線のばく露は、ゲノム不安定性を伴うがんのリスク要因となることが知られている。しかし、これらの外的ストレスによって生じた様々なタイプのDNA損傷のなかで、どのタイプの損傷が、どの様にゲノム不安定性の誘導に関わるのかは不明であった。本研究からは、放射線および紫外線で生じるDNA損傷とゲノム不安定性誘導の関係、特に、その作用点が明確になってきた。

Report

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

    (7 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Single base substitution signatures 17a, 17b, and 40 are induced by γ-ray irradiation in association with increased reactive oxidative species2024

    • Author(s)
      Manaka Yuya、Kusumoto-Matsuo Rika、Matsuno Yusuke、Asai Haruka、Yoshioka Ken-ichi
    • Journal Title

      Heliyon

      Volume: 10 Issue: 6 Pages: e28044-e28044

    • DOI

      10.1016/j.heliyon.2024.e28044

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome Destabilization-Associated Phenotypes Arising as a Consequence of Therapeutic Treatment are Suppressed by Olaparib2023

    • Author(s)
      Suzuki M., Fujimori H., Wakatsuki K., Manaka Y., Asai H., Hyodo M., Matsuno Y., Kusumoto-Matsuo R., Shiroishi M. and Yoshioka K.
    • Journal Title

      PLoS One

      Volume: 18 Issue: 1 Pages: e0281168-e0281168

    • DOI

      10.1371/journal.pone.0281168

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells2022

    • Author(s)
      Matsuno Yusuke、Kusumoto-Matsuo Rika、Manaka Yuya、Asai Haruka、Yoshioka Ken-ichi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 20964-20964

    • DOI

      10.1038/s41598-022-25479-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic Instability and Cancer Risk Associated with Erroneous DNA Repair.2021

    • Author(s)
      Yoshioka KI, Kusumoto-Matsuo R, Matsuno Y, Ishiai M.
    • Journal Title

      Int J Mol Sci.

      Volume: 22 Issue: 22 Pages: 12254-12254

    • DOI

      10.3390/ijms222212254

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Replication-stress-associated DSBs induced by ionizing radiation risk genomic destabilization and associated clonal evolution.2021

    • Author(s)
      Matsuno Y, Hyodo M, Suzuki M, Tanaka Y, Horikoshi Y, Murakami Y, Torigoe H, Mano H, Tashiro S, Yoshioka KI.
    • Journal Title

      iScience.

      Volume: 24 Issue: 4 Pages: 102313-102313

    • DOI

      10.1016/j.isci.2021.102313

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲノム安定性制御を作用点としたがん予防への挑戦2021

    • Author(s)
      吉岡研一
    • Organizer
      日本抗加齢医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 放射線で誘導される複製ストレスに起因したゲノム不安定性リスクとこれに伴うクローン進化2021

    • Author(s)
      吉岡研一
    • Organizer
      放射線影響学会
    • Related Report
      2021 Research-status Report

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

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