Biological effects of radioactive MnO2 particles

2021 Fiscal Year Research-status Report

• Project/Area Number: 19KK0266
• Research Institution: Hiroshima University
• Principal Investigator: 藤本 成明 広島大学, 原爆放射線医科学研究所, 准教授 (40243612)
• Co-Investigator(Kenkyū-buntansha): ムサジャノワ ジャンナ 長崎大学, 原爆後障害医療研究所, 助教 (30770432) ; 佐藤 斉 茨城県立医療大学, 保健医療学部, 教授 (90285057) ; 星 正治 広島大学, 平和センター, 名誉教授 (50099090)
• Project Period (FY): 2019-10-07 – 2023-03-31
• Keywords: 放射線微粒子被曝影響 / 放射性マンガン / 内部被曝

Outline of Annual Research Achievements

一般の放射線被ばく影響評価では、放射性微粒子による内部被ばく影響は外部被曝と同じとされている。しかし、原爆被曝者の疫学データや核実験場があったカザフスタンのセメイ市周辺地域での健康調査結果は、残留放射性物質による内部被曝の健康リスクは外部被爆に比べて大きいことを示している。したがって、その生物影響の詳細を確定することは、ヒト被曝影響の正確な評価と被曝防護において極めて重要である。本研究は、原爆爆発後に土中で多量に生成した放射性二酸化マンガンをモデルにし、放射性微粒子による内部被ばく影響を動物実験によって明らかにすることを目的とする。実験実施可能な施設を持つカザフスタンのセメイ医科大学およびカザフスタン国立核センターとの国際共同研究により、ラット及びマウスを用いた病理学的、分子生物学的な生物影響メカニズム解析を行う。
2021年度の研究は、2020年度同様にCOVID-19感染拡大によりカザフスタンとの人的研究交流が不可能となったこと、及びカザフスタン国内の感染状況の悪化に伴いセメイ医科大学とカザフスタン国立核センターの施設の利用が制限されたことにより大幅な変更となった。Web会議システムなどによる研究協力により以下の共同研究を実施した。1) 規模を縮小して実施したマウス曝露実験について、内部被曝線量の推定および曝露による病理学的変化について詳細に解析した。2) セメイ医科大学とのこれまでの共同研究で行ったラットへの放射性マンガン微粒子曝露実験から得られた材料について、肺組織および肝組織での遺伝子発現定量を中心とした詳細な被曝影響解析を行い非常に興味ある結果を得て公表した。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

COVID-19パンデミックの影響で、予定していたマウスへの放射性マンガン微粒子曝露実験について日本側の参加が不可能となり、大幅に縮小実施せざるを得なかったため。一方で、それ以前の共同研究で得た放射性マンガン微粒子曝露したラットの保存サンプルを用いた解析は順調に進み優れた成果を得た。

Strategy for Future Research Activity

２年間延期されていた以下の実験を実施する。
1) カザフスタン国立核研究センターの原子炉の中性子線によりMnO2微粒子を放射化し、10週齢の雄C57BLマウスへ曝露する。
2) 曝露後の動物を剖検し主要臓器の放射活性をγ線スペクトロメーターで測定する。動物体内での各臓器の放射活性からの相互の寄与をモンテカルロ法とマウス数学的形態モデルにより計算して、臓器ごとの吸収線量を推計する。
3) 曝露後3日、14日、60日で、各群５匹ずつを剖検し、主要組織をホルマリン及び核酸保存試薬でそれぞれ固定する。全臓器について病理組織学的検索を行い、影響の線量依存性を明らかにする。遺伝子発現レベル変動を指標にした生物学的線量計測法を応用して、放射線感受性遺伝子発現定量により56MnO2の内部被曝の特異性と線量依存性を解明する。

Causes of Carryover

COVID-19パンデミックによる影響で、予定していたカザフスタン・セメイ大学へ赴いての共同研究ができなかったため、セメイ医科大の研究施設利用費・旅費等を次年度に繰り越した。2022度は、この延期した曝露実験を実施するため繰り越し予算を用い、さらに2022年度請求した補助金を用いて放射線被曝影響解析研究を行う。

Research Products

• [Int'l Joint Research] Semey Medical University/Eurasian University/Kazkhstan National Nuclear Center(カザフスタン)
  • Country Name: KAZAKHSTAN
  • Counterpart Institution: Semey Medical University/Eurasian University/Kazkhstan National Nuclear Center
• [Journal Article] Biological impacts on the lungs in rats internally exposed to radioactive 56MnO2 particle (2021)
  • Author(s): Fujimoto Nariaki、Ruslanova Bakhyt、Abishev Zhaslan、Chaizhunussova Nailya、Shabdarbayeva Dariya、Amantayeva Gaukhar、Farida Rakhimzhanova、Sandybayev Marat、Nagano Kasuke、Zhumadilov Kassym、Kaprin Andrey、Ivanov Sergey、Stepanenko Valeriy、Hoshi Masaharu
  • Journal Title: Scientific Reports Volume: 11 Pages: 11055
  • DOI: 10.1038/s41598-021-90443-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive 56MnO2 Particles at Low Doses (2021)
  • Author(s): Ruslanova Bakhyt、Abishev Zhaslan、Chaizhunussova Nailya、Shabdarbayeva Dariya、Tokesheva Sholpan、Amantayeva Gaukhar、Kairkhanova Ynkar、Stepanenko Valeriy、Hoshi Masaharu、Fujimoto Nariaki
  • Journal Title: Current Issues in Molecular Biology Volume: 43 Pages: 758～766
  • DOI: 10.3390/cimb43020055
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid (2021)
  • Author(s): Matsuu-Matsuyama Mutsumi、Shichijo Kazuko、Matsuda Katsuya、Fujimoto Nariaki、Kondo Hisayoshi、Miura Shiro、Kurashige Tomomi、Nagayama Yuji、Nakashima Masahiro
  • Journal Title: Scientific Reports Volume: 11 Pages: 19096
  • DOI: 10.1038/s41598-021-98481-z
  • Peer Reviewed
• [Journal Article] Single neonatal irradiation induces long-term gene expression changes in the thyroid gland, which may be involved in the tumorigenesis (2021)
  • Author(s): Fujimoto Nariaki、Matsuu-Matsuyama Mutsumi、Nakashima Masahiro
  • Journal Title: Scientific Reports Volume: 11 Pages: 23620
  • DOI: 10.1038/s41598-021-03012-5
  • Peer Reviewed
• [Journal Article] 53BP1 expression as a biomarker to differentiate thyroid follicular tumors (2021)
  • Author(s): Sato Ayako、Matsuda Katsuya、Motoyama Takahiro、Mussazhanova Zhanna、Otsubo Ryota、Kondo Hisayoshi、Akazawa Yuko、Higuchi Miyoko、Suzuki Ayana、Hirokawa Mitsuyoshi、Miyauchi Akira、Nagayasu Takeshi、Nakashima Masahiro
  • Journal Title: Endocrine Connections Volume: 10 Pages: 309～315
  • DOI: 10.1530/EC-20-0630
  • Peer Reviewed
• [Journal Article] The Contribution of Genetic Variants to the Risk of Papillary Thyroid Carcinoma in the Kazakh Population: Study of Common Single Nucleotide Polymorphisms and Their Clinicopathological Correlations (2021)
  • Author(s): Mussazhanova Z、Rogounovitch TI.、Saenko VA.、Krykpayeva A、Espenbetova M、Azizov B、Kondo H、Matsuda K、Kalmatayeva Z、Issayeva R、Yeleubayeva Zhanar、Madiyeva Madina、Mukanova Aray、Sandybayev Marat、Bolsynbekova Saltanat、Kozykenova Zhanna、Yamashita Shunichi、Nakashima Masahiro
  • Journal Title: Frontiers in Endocrinology Volume: 11 Pages: 543500
  • DOI: 10.3389/fendo.2020.543500
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An Exploration of the Labor, Financial, and Economic Factors Related to Suicide in the Republic of Kazakhstan (2021)
  • Author(s): Inoue Ken、Seksenbayev Nursultan、Chaizhunusova Nailya、Moldagaliyev Timur、Ospanova Nargul、Tokesheva Sholpan、Zhunussov Yersin T.、Takeichi Nobuo、Noso Yoshihiro、Hoshi Masaharu、Kawano Noriyuki
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 18 Pages: 6992～6992
  • DOI: 10.3390/ijerph18136992
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Early detection of excessive stress in people due to the ongoing COVID-19 pandemic: studies including those using biological markers (2021)
  • Author(s): Fujita Yasuyuki、Inoue Ken、Seksenbayev Nursultan、Chaizhunusova Nailya、Hoshi Masaharu、Kawano Noriyuki、Takeichi Nobuo、Moldagaliyev Timur、Ospanova Nargul、Tokesheva Aigul、Zhunussov Yersin T.、Noso Yoshihiro、Ohira Yoshiyuki
  • Journal Title: International Maritime Health Volume: 72 Pages: 143～144
  • DOI: 10.5603/IMH.2021.0025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A combined scientific and public health approach is needed to evaluate the health impacts of internal exposure to radiation (2021)
  • Author(s): Inoue Ken、Kawano Noriyuki、Takeichi Nobuo、Noso Yoshihiro、Hoshi Masaharu
  • Journal Title: The Lancet Regional Health - Western Pacific Volume: 15 Pages: 100296～100296
  • DOI: 10.1016/j.lanwpc.2021.100296
  • Peer Reviewed
• [Journal Article] Characteristic evaluation of a simple hand-made semiconductor dosimeter for mammography (2021)
  • Author(s): Nakajima Erika、Yamashita Hiromi、Sato Hitoshi
  • Journal Title: Journal of Radiological Protection Volume: 41 Pages: 1018～1033
  • DOI: 10.1088/1361-6498/ac20b2
  • Peer Reviewed
• [Journal Article] Occupational eye lens dose in endoscopic retrograde cholangiopancreatography using a dedicated eye lens dosimeter (2021)
  • Author(s): Imai Shinya、Akahane Manabu、Ogata Yuji、Tanki Nobuyoshi、Sato Hitoshi、Tameike Kazuma
  • Journal Title: Journal of Radiological Protection Volume: 41 Pages: 579～589
  • DOI: 10.1088/1361-6498/ac091f
  • Peer Reviewed
• [Presentation] Animal studies of 56MnO2 exposure in 2018-19 (2022)
  • Author(s): Fujimoto N
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research / Invited
• [Presentation] Overview of our studies of radiation effects in Kazakhstan (2022)
  • Author(s): Hoshi M
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research / Invited
• [Presentation] Study of 7Be and 210Pb in atmosphere of Akmola region of Kazakhstan (2022)
  • Author(s): Kassym Zhumadilov, Aidana Zhumalina, Yernaz Sambayev, Yeldos Bekzhanov, Asel Bagramova, Tulegen Kusainov, Aya Sakaguchi, Satoru Endo, Shin Toyoda, Hitoshi Sato, Masaharu Hoshi,
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] Trial of remote thyroid examination 10 years after the Fukushima nuclear power accident in COVID-19 pandemic (2022)
  • Author(s): Yoshihiro Noso, Atsuko Imagawa, Akio Haruta, Motomi Ushiyama, Takashi Sawada, Laura Pak, Nailya Chaizhunussova, Ken Inoue, Nobuo Takeichi, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] Anxiety and fear about mental and physical health for radiation exposure in the people -importance of dissemination about correct knowledge based on the cooperation in various fields (2022)
  • Author(s): Ken Inoue, Noriyuki Kawano, Nailya Chaizhunussova, Nursultan Seksenbayev, Madina Apbassova, Nobuo Takeichi, Yoshihiro Noso, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] Effects of internal exposure to neutron-activated 56MnO2 powder on locomotor activity in rats (2022)
  • Author(s): Keiko Otani, Megu Ohtaki, Nariaki Fujimoto, Darkhan Uzbekov, Ynkar Kairkhanova, Aisulu Saimova, Nailya Chaizhunussova, Dariya Habdarbaeva, Almas Azhimkhanov, Kassym Zhumadilov, Valeriy Stepanenko, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] The effect of various doses of ionizing radiation on liver tissue in experiment (2022)
  • Author(s): Bakhyt Ruslanova, Nailya Chaizhunussova, Dariya Shabdarbayeva, Nariaki Fujimoto, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] The effects of internal and external exposure on morphological indicators and gene expression in lungs in experiment (rats and mice) (2022)
  • Author(s): Zhaslan Abishev, Nailya Chaizhunussova, Dariya Shabdarbayeva, Nariaki Fujimoto, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] Influence of internal and external ionizing radiation on gene expression of the reproductive system in male laboratory animals. (2022)
  • Author(s): Nailya Chaizhunussova, Gauhar Amantayeva, Dariya Shabdarbayeva, Nariaki Fujimoto, Masaharu Hoshi
  • Organizer: The 24th Hiroshima International Symposium: Research on radiation and its effects in Kazakhstan and other countries
  • Int'l Joint Research
• [Presentation] Interlaboratory comparison of EPR tooth enamel dosimetry with investigations of the dose responses of the standard samples (2022)
  • Author(s): Toyoda, S., Inoue, K., Yamaguchi, I., Hoshi, M., Hirota, S., Oka, T., Shimazaki, T., Mizuno, H., Tani, A., Yasuda, H., Gonzales, C. A. B., Okutsu, K., Takahashi, A., Tanaka, N., Todaka, A
  • Organizer: EPR BioDose 2022
  • Int'l Joint Research
• [Presentation] ラット新生仔期被曝による甲状腺腫瘍化に関与する遺伝子発現変化(O2-7-1) (2021)
  • Author(s): 藤本成明, 松山睦美, 中島正洋
  • Organizer: 第94回日本内分泌学会学術総会
• [Presentation] 放射性56MnO2 微粒子曝露による低線量被曝でのラット雄性生殖線機能低下 (2021)
  • Author(s): 藤本成明, 星正治, Chaizhunussova N
  • Organizer: 第5回放射線災害 医科学研究拠点カンファランス
• [Presentation] Biological effects of radioactive particles produced by atomic bombing; animal studies (2021)
  • Author(s): Fujimoto N
  • Organizer: 15th international scientific-practical conference ecology. radiation. health, Semey, Kazakhstan
  • Int'l Joint Research / Invited
• [Presentation] Biological effects of internal exposure to radioactive particles of 56MnO2 in rats (2021)
  • Author(s): Fujimoto N, Chaizhunussova N, Shabdarbayeva D, Gnyrya V, Azhimkhanov A, Kolbayenkov A, Zhumadilov K, Stepanenko V, Hoshi M
  • Organizer: 9th international conference semipalatinsk test site, Kurchatov, Kazakhstani
  • Int'l Joint Research
• [Presentation] International collaboration of radiation risk evaluation in Semipalatinsk, 4th dosimetry and health risk assessment in the Semipalatinsk cohort of subjects (2021)
  • Author(s): Hoshi M
  • Organizer: 4th Dosimetry Meeting
  • Int'l Joint Research
• [Presentation] Animal exposure experiments using Mn-56 dioxide radioactive microparticles, (2021)
  • Author(s): Hoshi M, Chaizhunusova N, Zhumadilov K, Uzbekov D, Shabdarbaeva D, Kairkhanova Y, Amantaeva G, Ruslanova B, Apbassova M et al
  • Organizer: 9th international conference semipalatinsk test site, Kurchatov, Kazakhstani
  • Int'l Joint Research
• [Presentation] International collaboration between Kazakhstan and Japan; Studies with Shakarim University (2021)
  • Author(s): M. Hoshi, S. Duyssembayev, Z. Serikov, A. Klivenko, K. Zhumadilov, A. Zhumalina, P. Kazymbet, M. Bakhtin, A. Sakaguchi, M. Yamamoto, S. Endo, H. Satoh, S. Toyoda, N. Kawano
  • Organizer: Shakarim University Symposium
  • Int'l Joint Research