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Mechanism of low dose(rate) radiation induced tumor development by using intestinal stem cell organoid system

Research Project

Project/Area Number 17K00553
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionHiroshima University

Principal Investigator

Sasatani Megumi  広島大学, 原爆放射線医科学研究所, 准教授 (80423052)

Co-Investigator(Kenkyū-buntansha) 河合 秀彦  広島大学, 医系科学研究科(薬), 准教授 (30379846)
神谷 研二  広島大学, 医療政策室, 特任教授 (60116564)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords放射線 / 発がん / 低線量(率) / 幹細胞 / 動物モデル / 低線量・低線量率 / 放射線発がん / 年齢依存性 / 低線量(率)放射線発がんリスク
Outline of Final Research Achievements

It is known that radiation-induced cancer risk in childhood is higher than in adulthood in human. Thus, age at exposure is a major effect modifier of radiation-induced cancer. Given that the Fukushima Daiichi Nuclear Power Plant accident in Japan is reviving concern about cancer risk at low radiation doses, especially in childhood, clarifying the mechanism of susceptibility for radiation-induced carcinogenesis in childhood needs to be investigated in each organ. The application of animal models might be useful for understanding the mechanism of age-dependent cancer risk. Here, we elucidated the age dependence of the exposure in model mice of intestinal tumors, and analyzed the effects of radiation response and age on irradiation on carcinogenesis, including cell competition of small intestinal stem cells. And our results suggest that there is the relationship between intestinal morphogenesis and radiation-induced cancer risk.

Academic Significance and Societal Importance of the Research Achievements

福島原発事故後、胎児期・小児期被ばくにおける発がんリスクの増加が懸念されている。しかしながら、放射線発がんにおける被ばく時年齢依存性の有無とその分子メカニズムについては未だ未解明の部分が多い。そのため、本研究成果は、動物モデルを用いて放射線発がんにおける被ばく時年齢依存性の機構解明に関する新規知見が得られており、学術的に重要といえる。また、各年齢における放射線発がんリスクとその分子機構が解明されれば、放射線発がんリスク評価のみならず放射線防護体系の基盤確立に貢献できることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Invited: 2 results)

  • [Journal Article] The in vivo role of Rev1 in mutagenesis and carcinogenesis2020

    • Author(s)
      Sasatani Megumi、Zaharieva Elena Karamfilova、Kamiya Kenji
    • Journal Title

      Genes and Environment

      Volume: 42 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s41021-020-0148-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A chemical modulator of p53 transactivation that acts as a radioprotective agonist.2018

    • Author(s)
      Akinori Morita, Ippei Takahashi, Megumi Sasatani, Shin Aoki, Bing Wang, Shinya Ariyasu, Kaoru Tanaka, Tetsuji Yamaguchi, Akiko Sawa, Yurie Nishi, Tatsuro Teraoka, Shohei Ujita, Yosuke Kawate, Chihiro Yanagawa, Keiji Tanimoto, Atsushi Enomoto, Mitsuru Nenoi, Kenji Kamiya, Yasushi Nagata, Yoshio Hosoi and Toshiya Inaba
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 17 Issue: 2 Pages: 432-442

    • DOI

      10.1158/1535-7163.mct-16-0554

    • NAID

      120006552353

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATM-mediated mitochondrial damage response triggered by nuclear DNA damage in normal human lung fibroblasts.2017

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

      Cell Cycle.

      Volume: 16(24) Issue: 24 Pages: 2345-2354

    • DOI

      10.1080/15384101.2017.1387697

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Rev1 promotes the development of carcinogen-induced intestinal adenomas via accumulation of point mutation and suppression of apoptosis proportionally to the Rev1 expression level.2017

    • Author(s)
      Sasatani M, Xi Y, Kajimura J, Kawamura T, Piao J, Masuda Y, Honda H, Kubo K, Mikamoto T, Watanabe H, Xu Y, Kawai H, Shimura T, Noda A, Hamasaki K, Kusunoki Y, Zaharieva EK, Kamiya K.
    • Journal Title

      Carcinogenesis.

      Volume: 38(5) Issue: 5 Pages: 570-578

    • DOI

      10.1093/carcin/bgw208

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of induced pluripotent stem cells from normal B cells and inducing AID expression in their differentiation into hematopoietic progenitor cells2017

    • Author(s)
      Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yu Abe, Naohiro Tsuyama, Yumiko Kurosu, Aki Yanagi, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Mitsuaki A. Yoshida, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera & Akira Sakai
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-017-01627-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The effect of dose rate on intestinal adenoma development in ApcMin/+ mice2020

    • Author(s)
      Megumi Sasatani, Elena Zaharieva, Kenji Kamiya
    • Organizer
      4th International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
    • Related Report
      2019 Annual Research Report
  • [Presentation] ApcMin/+マウスを用いた低線量・低線量率放射線発がんリスク評価2019

    • Author(s)
      笹谷めぐみ
    • Organizer
      56回アイソトープ・放射線研究発表会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Elucidation of radiation-induced tumor risk at low doses and low dose rates by using ApcMin/+ mice2019

    • Author(s)
      Megumi Sasatani, Kazutaka Doi, Daisuke Iizuka, Kenji Kamiya
    • Organizer
      日本放射線影響学会第62回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Apc Min/+マウスを用いた放射線誘発腫瘍における遺伝子変異解析2019

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 河合秀彦, Zaharieva Elena, 神谷研二
    • Organizer
      第6回アジア環境変異原学会/日本環境変異原学会第48回大会合同大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 動物モデルを用いた低線量・低線量率発がんリスク評価. 第3回 放射線災害・医科学研究拠点カンファランス2019

    • Author(s)
      笹谷めぐみ, 土居主尚, 神谷研二
    • Organizer
      第3回 放射線災害・医科学研究拠点カンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] 放射線発がんに高感受性であるApcMin/+マウスを用いた低線量放射線発がんリスク評価2019

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 土居主尚, 神谷研二
    • Organizer
      原子爆弾後障害研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] ApcMin/+マウスを用いた放射線誘発小腸腫瘍形成の機構解明2019

    • Author(s)
      笹谷めぐみ, 神谷研二
    • Organizer
      第31回夏の学校
    • Related Report
      2018 Research-status Report
  • [Presentation] Apc Min/+マウスを用いた放射線誘発腫瘍における遺伝子変異解析2019

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 河合秀彦, Zaharieva Elena, 神谷研二
    • Organizer
      日本環境変異原学会第47回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Apc Min/+マウスを用いた低線量放射線発がんリスク評価2019

    • Author(s)
      笹谷めぐみ, 土居主尚, 飯塚大輔, 神谷研二
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Estimation of radiation-induced cancer risk at low doses and low dose rates using ApcMin/+ mice2019

    • Author(s)
      Megumi Sasatani, Daisuke Iizuka, Hidehiko Kawai, Elena Zaharieva, Kenji Kamiya,
    • Organizer
      3rd International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
    • Related Report
      2018 Research-status Report
  • [Presentation] 放射線発がん高感受性マウスを用いた低線量・低線量率発がんリスク評価2017

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 河合秀彦, Zaharieva Elena, 神谷研二
    • Organizer
      第2回 放射線災害・医科学研究拠点カンファランス
    • Related Report
      2017 Research-status Report
  • [Presentation] 遺伝的背景が放射線発がん高感受性モデルマウスの腫瘍形成に与える影響について2017

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 河合秀彦, Zaharieva Elena, 神谷研二
    • Organizer
      第58回 原子爆弾後障害研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 発がん高感受性マウスを用いた化学発がん、放射線発がんの機構解明2017

    • Author(s)
      笹谷めぐみ
    • Organizer
      平成29年度日本環境変異原学会 公開シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] マウス個体を用いた低線量率放射線被ばくの生物影響について2017

    • Author(s)
      笹谷 めぐみ、飯塚 大輔、河合 秀彦、Zaharieva Elena、神谷 研二
    • Organizer
      第42回中国地区放射線影響研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Genetic mutation analysis in ionizing radiation (IR)-induced adenoma in ApcMin/+ mice2017

    • Author(s)
      Megumi Sasatani, Daisuke Iizuka, Kenji Kamiya
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Apc Min/+マウスを用いた低線量、低線量率放射線発がんリスク評価2017

    • Author(s)
      笹谷 めぐみ、飯塚 大輔、河合 秀彦、Zaharieva Elena、神谷 研二
    • Organizer
      第60回日本放射線影響学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Apc Min/+マウスを用いた放射線誘発腫瘍における遺伝子変異の検出2017

    • Author(s)
      笹谷 めぐみ、飯塚 大輔、河合 秀彦、Zaharieva Elena、神谷 研二
    • Organizer
      日本環境変異原学会第46回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ApcMin/+マウスを用いた低線量、低線量率放射線発がんリスク評価の試みとその腫瘍解析2017

    • Author(s)
      笹谷めぐみ, 飯塚大輔, 河合秀彦, Elena Zaharieva, 神谷研二
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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