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Effect of autophagy on the sensitivity and carcinogenesis of the rat thyroid to ionizing radiation

Research Project

Project/Area Number 17K00554
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 InstitutionNagasaki University

Principal Investigator

MATSUYAMA Mutsumi  長崎大学, 原爆後障害医療研究所, 助教 (00274639)

Co-Investigator(Kenkyū-buntansha) 中島 正洋  長崎大学, 原爆後障害医療研究所, 教授 (50284683)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsX線 / ラット / 甲状腺 / 発癌 / オートファジー / 増殖細胞 / 発がん / X線
Outline of Final Research Achievements

To investigate the involvement of autophagy (AP) in radiation-induced thyroid cancer, hydroxychloroquine (HCQ) 200 mg / kg or saline was orally administered to 6-week-old male Wistar rats for 3 days before irradiation, and after 4 Gy whole body / local irradiation or non-irradiation, the acute radiation response of the thyroid gland and the tumor incidence in the chronic phase were investigated by dividing it into a non-irradiated non-treatment group, a non-irradiated HCQ group, a irradiated non-treatment group and a irradiated HCQ group. In the acute phase, a decrease in the number of proliferating cells and a decrease in AP-related genes were observed. Thyroid tumors were 14/15 (93.3%) in the untreated irradiated group, 9/13 (69.2%) in the HCQ group, and they were low in the HCQ group (p = 0.097). It is suggested that HCQ pretreatment may be suppressed tumor development, but further studies are needed.

Academic Significance and Societal Importance of the Research Achievements

これまでに、放射線被曝甲状腺の急性期応答として、若齢ラットでは高齡ラットと比べオートファジー関連分子の発現が促進するが、照射後慢性期の発癌時期では一部のオートファジー構成因子の遺伝子発現が低下することを見出している。「若年被曝ではオートファジーにより濾胞上皮細胞の生存に作用し、加齢とともにオートファジーの機能が抑制され、被曝細胞のうち細胞死に陥らない細胞が腫瘍化する」という仮説を検証する。甲状腺発癌早期からの動物モデルでのオートファジー機能研究はこれまでになく独創的で、若年被曝の甲状腺発癌リスク亢進の分子機構の解明に寄与する目的として、有意義なテーマとなる。

Report

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

    (25 results)

All 2020 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 4 results) Remarks (3 results)

  • [Journal Article] Morphological and functional changes in neonatally X-irradiated thyroid gland in rats2020

    • Author(s)
      Fujimoto Nariaki、Matsuu-Matsuyama Mutsumi、Nakashima Masahiro
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 2 Pages: 231-240

    • DOI

      10.1507/endocrj.EJ19-0245

    • NAID

      130007802880

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective effects of a cystine and theanine mixture against acute radiation injury in rats2020

    • Author(s)
      Matsuu-Matsuyama Mutsumi、Shichijo Kazuko、Tsuchiya Takashi、Kondo Hisayoshi、Miura Shiro、Matsuda Katsuya、Sekine Ichiro、Nakashima Masahiro
    • Journal Title

      Environmental Toxicology and Pharmacology

      Volume: 78 Pages: 103395-103395

    • DOI

      10.1016/j.etap.2020.103395

    • NAID

      120006988216

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集 甲状腺腫瘍―変貌する疾患概念― 放射線と甲状腺発がん2020

    • Author(s)
      中島正洋
    • Journal Title

      病理と臨床

      Volume: 38(2) Pages: 156-162

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 甲状腺特異的オートファジーノックアウトマウスでは、濾胞上皮細胞死が誘導される2020

    • Author(s)
      永山雄二、蔵重智美、中島康代、嶋村美加、松山睦美、中島正洋、山田正信
    • Journal Title

      日本内分泌学会雑誌(会議録)

      Volume: 95(4) Pages: 1335-1335

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice2019

    • Author(s)
      Kurashige Tomomi、Nakajima Yasuyo、Shimamura Mika、Matsuyama Mutsumi、Yamada Masanobu、Nakashima Masahiro、Nagayama Yuji
    • Journal Title

      Endocrinology

      Volume: 160 Issue: 9 Pages: 2085-2092

    • DOI

      10.1210/en.2019-00312

    • NAID

      120006988409

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ラット新生仔期甲状腺への放射線被曝で誘発される甲状腺機能不全2019

    • Author(s)
      藤本成明、松山睦美、中島正洋
    • Journal Title

      日本内分泌学会雑誌

      Volume: 95(1) Pages: 449-449

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Autoradiographic analysis of internal plutonium radiation exposure in Nagasaki atomic bomb victims.2018

    • Author(s)
      1.Shichijo K, Takatsuji T, Fukumoto M, Nakashima M, Matsuyama M and Sekine I
    • Journal Title

      Heliyon

      Volume: 4 (6) Issue: 6 Pages: e00666-e00666

    • DOI

      10.1016/j.heliyon.2018.e00666

    • NAID

      120006988005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 新生仔ラット甲状腺の電離放射線への感受性2018

    • Author(s)
      藤本成明、松山睦美、中島正洋
    • Journal Title

      長崎医学会雑誌

      Volume: 93号特集号 Pages: 361-362

    • Related Report
      2018 Research-status Report
  • [Journal Article] アミノ酸混合物シスチン・テアニンの放射線防護効果:前投与による急性小腸・骨髄障害と長期生存率への影響2018

    • Author(s)
      松山睦美、七條和子、土屋 誉、米田純也、近藤久義、松田勝也、三浦史郎、関根一郎、中島正洋
    • Journal Title

      長崎医学会雑誌

      Volume: 93号特集号 Pages: 367-369

    • Related Report
      2018 Research-status Report
  • [Journal Article] 長崎原爆被爆者組織バンクの経過報告(第4報):凍結保存期間とRNAの品質について2018

    • Author(s)
      三浦史郎、近藤久義、松田勝也、ムサジャノワジャンナ、松山睦美、中島正洋
    • Journal Title

      広島医学

      Volume: 71(4) Pages: 335-338

    • Related Report
      2018 Research-status Report
  • [Journal Article] Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells2017

    • Author(s)
      Doi Ryoichiro, Tsuchiya Tomoshi, Mitsutake Norisato, Nishimura Satoshi, Matsuu-Matsuyama Mutsumi, Nakazawa Yuka, Ogi Tomoo, Akita Sadanori, Yukawa Hiroshi, Baba Yoshinobu, Yamasaki Naoya, Matsumoto Keitaro, Miyazaki Takuro, Kamohara Ryotaro, Hatachi Go, Sengyoku Hideyori et al.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41598-017-09115-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Age-dependent effects on radiation-induced thyroid cancer and autophagy-related gene expression with rat model.2019

    • Author(s)
      3.Matsuu-Matsuyama M, Shichijo K, Matsuda K, Miura S, Kondo H, Nakashima M
    • Organizer
      16th International Congress of Radiation Research 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット甲状腺に急性期放射線感受性におけるオートファジーの影響2019

    • Author(s)
      松山睦美、七條和子、松田勝也、三浦史郎、近藤久義、中島正洋
    • Organizer
      第60回原子爆弾後障害研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ラット甲状腺の急性期放射線感受性におけるオートファジー阻害剤ヒドロキシクロロキンの影響2019

    • Author(s)
      松山睦美、七條和子、松田勝也、三浦史郎、近藤久義、中島正洋
    • Organizer
      日本放射線影響学会第62回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ラット新生仔期甲状腺への放射線被曝で誘発される甲状腺機能不全2019

    • Author(s)
      藤本成明、松山睦美、中島正洋
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice2019

    • Author(s)
      Yuji Nagayama, Tomomi Kurashige, Mika Shimamura, Mutsumi Matsuyama and Masahiro Nakashima
    • Organizer
      The 3rdInternational Symposium of the Network-type Joint Usage Research Center for Radiation Disaster Medical Science
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protective effects of amino acid mixture cystine and theanine: Effects on acute radiation injury of colon2019

    • Author(s)
      Kazuko Shichijo, Mutsumi Matsuyama, Takashi Tsuchiya, Junya Yoneda, Hisayoshi Kondo, Katsuya Matsuda, Shiro Miura, Ichiro Sekine and Masahiro Nakashima
    • Organizer
      The 3rdInternational Symposium of the Network-type Joint Usage Research Center for Radiation Disaster Medical Science
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] アミノ酸混合物シスチン・テアニンの放射線防護効果:前投与のよる急性小腸・骨髄障害と長期生存率への影響2018

    • Author(s)
      松山睦美、七條和子、土屋 誉、米田純也、近藤久義、松田勝也、三浦史郎、関根一郎、中島正洋
    • Organizer
      第59回原子爆弾後障害研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Protective effects of amino acids cystine and theanine against radiation injury of colon2018

    • Author(s)
      Kazuko Shichijo, Mutsumi Matsuyama, Hisayoshi Kondo, Takashi Tuchiya, Junya Yoneda, Katsuya Matsuda, Shiro Miura, Ichiro Sekine and Masahiro Nakashima
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Protective effects of amino acid mixture cystine and theanine on acute radiation-injury of small intestine2018

    • Author(s)
      Mutsumi Matsuyama, Kazuko Shichijo, Takashi Tsuchiya, Junya Yoneda, Hisayoshi Kondo, Katsuya Matsuda, Shiro Miura, Ichiro Sekine, Masahiro Nakashima
    • Organizer
      The 2nd International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] アミノ酸混合物シスチン・テアニンの放射線防護効果:急性小腸障害への影響2017

    • Author(s)
      9.松山睦美、七條和子、近藤久義、土屋 誉、米田純也、松田勝也、三浦史郎、関根一郎、中島正洋
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] アミノ酸混合物シスチン・テアニンの放射線防護効果:前投与による生存率と急性小腸障害への影響2017

    • Author(s)
      1.松山睦美、七條和子、近藤久義、土屋 誉、米田純也、松田勝也、三浦史郎、関根一郎、中島正洋
    • Organizer
      第60回日本放射線影響学会
    • Related Report
      2017 Research-status Report
  • [Remarks] 長崎大学原爆後障害医療研究所 腫瘍・診断病理学研究分野(原研病理)

    • URL

      https://www-sdc.med.nagasaki-u.ac.jp/pathology/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 長崎大学原爆後障害医療研究所 腫瘍・診断病理学研究分野 (原研病理)

    • URL

      https://users.tls-style.jp/nagasaki-u/pathology/

    • Related Report
      2018 Research-status Report
  • [Remarks] 長崎大学原爆後障害医療研究所 腫瘍・診断病理学研究分野(原研病理)

    • URL

      http://www-sdc.med.nagasaki-u.ac.jp/pathology/index.html

    • Related Report
      2017 Research-status Report

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

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