The effect of low-dose radiation exposure on germ cells in laboratory mouse and application trials in wild mouse.

• Project/Area Number: 20K12192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63040:Environmental impact assessment-related
• Research Institution: Hokkaido University of Science
• Principal Investigator: Nakata Akifumi 北海道科学大学, 薬学部, 准教授 (70415420)
• Co-Investigator(Kenkyū-buntansha): 三浦 富智 弘前大学, 被ばく医療総合研究所, 教授 (20261456) ; 山城 秀昭 新潟大学, 自然科学系, 准教授 (60612710) ; 篠田 壽 東北大学, 歯学研究科, 名誉教授 (80014025) ; 後藤 淳 新潟大学, 研究推進機構, 助教 (90370395)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 放射線 / 生殖腺 / 遺伝子発現 / メチル化 / 野生動物 / 生殖細胞 / 実験動物 / 生殖影響

Outline of Research at the Start

本研究では、放射線照射したラボマウスにおける体細胞および生殖細胞サンプルから染色体やエピジェネティクスな挙動、放射線に感受性のある遺伝子の解析を行い、放射性物質汚染地域に生息するアカネズミに生じた繁殖活動および生殖細胞における放射線の影響を評価する。
さらに、放射線照射したラボマウスから産子作出を行い、継世代影響の評価を担保することで、ラボとフィールドの双方に外挿できるモデルの開発を行い、放射線量が低減化している居住地域への住民の帰還の判断材料となる情報を提示する。

Outline of Final Research Achievements

In this study, we analyzed the effects of radiation on germ cells by conducting gene expression and genome-wide methylation analysis in the testes of laboratory mice exposed to acute high-dose ionizing radiation and chronic low-dose ionizing radiation. Our findings revealed alterations in genes expression involved in epigenetic regulation due to radiation exposure. Furthermore, we observed methylated regions not only in promoter regions but also in exon regions of the testes, without detecting clear differences attributed to radiation exposure. Additionally, we performed de novo assembly of contigs using RNA-seq in the field model animal, Apodemus speciosus, collected from radiation-contaminated areas.

Academic Significance and Societal Importance of the Research Achievements

慢性的な低線量長期被ばくによる生殖器官や生殖細胞への継世代影響に関する知見は限られている。本研究は、放射線による生物影響として、エピジェネティック制御に関与する遺伝子の発現とDNAメチル化の解析を行った。放射線照射したラボマウスの精巣では、遺伝子発現の変化がエピゲノムの変動を引き起こす可能性が示唆された。また、放射性物質汚染地域に生息する放射線影響モデル動物の遺伝的評価可能となれば、環境保護や公衆衛生の観点から低線量放射線被ばくに関するリスク評価において有用であることが期待される。

Research Products

• [Journal Article] Exosome-like vesicles released from ob/ob mouse adipose tissue enhance cell survival of cells with radiation-induced genomic instability (2023)
  • Author(s): Kentaro Ariyoshi, Yohei Fujishima, Valerie Swee Ting Goh, Akifumi Nakata, Kosuke Kasai, Mitsuaki A. Yoshida, Tomisato Miura
  • Journal Title: Journal of radiation research Volume: 64(2) Issue: 2 Pages: 352-357
  • DOI: 10.1093/jrr/rrac102
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytogenetic Biodosimetry in Radiation Emergency Medicine: 3. The Basics of Chromosomes for Biodosimetry (2022)
  • Author(s): Nakata A, Ariyoshi K, Abe Y, Fujishima Y, Goh VST, Nakayama R, Takebayashi K, Tran TM, Kasai K, Yoshida MA, Miura T.
  • Journal Title: Radiation Environment and Medicine Volume: 11 Issue: 2 Pages: 82-90
  • DOI: 10.51083/radiatenvironmed.11.2_82
  • ISSN: 2423-9097, 2432-163X
  • Year and Date: 2022-08-29
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytogenetic Biodosimetry in Radiation Emergency Medicine: 4. Overview of Cytogenetic Biodosimetry (2022)
  • Author(s): Nakayama R, Abe Y, Goh VST, Takebayashi K, Tran TM, Fujishima Y, Nakata A, Ariyoshi K, Kasai K, Anderson D, Hanada H, Yoshida MA, Ito K, Miura T.
  • Journal Title: Radiation Environment and Medicine Volume: 11 Issue: 2 Pages: 91-103
  • DOI: 10.51083/radiatenvironmed.11.2_91
  • ISSN: 2423-9097, 2432-163X
  • Year and Date: 2022-08-29
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytogenetic Biodosimetry in Radiation Emergency Medicine: 1. Blood Collection and Its Management (2022)
  • Author(s): Yohei Fujishima, Yu Abe, Valerie Goh Swee Ting, Ryo Nakayama, Kai Takebayashi, Akifumi Nakata, Kentaro Ariyoshi, Mai Tran Thanh, Kosuke Kasai, Hiroyuki Hanada, Mitsuaki A. Yoshida, Katsuhiro Ito, Tomisato Miura
  • Journal Title: Radiation Environment and Medicine Volume: 11 Issue: 1 Pages: 25-33
  • DOI: 10.51083/radiatenvironmed.11.1_25
  • ISSN: 2423-9097, 2432-163X
  • Year and Date: 2022-02-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytogenetic Biodosimetry in Radiation Emergency Medicine: 2. Biosafety and Chemical Safety in Biodosimetry Laboratory (2022)
  • Author(s): Kosuke Kasai, Yu Abe, Valerie Goh Swee Ting, Mai Tran Thanh, Yohei Fujishima, Ryo Nakayama, Kai Takebayashi, Akifumi Nakata, Kentaro Ariyoshi, Hiroyuki Hanada, Mitsuaki A. Yoshida, Katsuhiro Ito, Tomisato Miura
  • Journal Title: Radiation Environment and Medicine Volume: 11 Issue: 1 Pages: 34-39
  • DOI: 10.51083/radiatenvironmed.11.1_34
  • ISSN: 2423-9097, 2432-163X
  • Year and Date: 2022-02-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of sperm fertilization capacity of large Japanese field mice (Apodemus speciosus) exposed to chronic low dose-rate radiation after the Fukushima accident (2022)
  • Author(s): Nihei Kazu、Tokita Syun、Yamashiro Hideaki、Swee Ting Valerie Goh、Nakayama Ryo、Fujishima Yohei、Kino Yasushi、Shimizu Yoshinaka、Shinoda Hisashi、Ariyoshi Kentaro、Kasai Kosuke、Abe Yasuyuki、Fukumoto Manabu、Nakata Akifumi、Miura Tomisato
  • Journal Title: Journal of Radiation Research and Applied Sciences Volume: 15 Issue: 3 Pages: 186-190
  • DOI: 10.1016/j.jrras.2022.07.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human Resource Development for Cytogenetic Biodosimetry at Hirosaki University (2021)
  • Author(s): Tomisato Miura, Kosuke Kasai, Yu Abe, Yohei Fujishima, Valerie Goh Swee Ting, Ryo Nakayama, Kai Takebayashi, Naomi Sasaki, Kentaro Ariyoshi, Akifumi Nakata, Takakiyo Tsujiguchi, Katsuhiro Ito, Hiroyuki Hanada, Mitsuaki A. Yoshida
  • Journal Title: Radiation Environment and Medicine Volume: 10 Issue: 2 Pages: 102-107
  • DOI: 10.51083/radiatenvironmed.10.2_102
  • NAID: 40022662262
  • ISSN: 2423-9097, 2432-163X
  • Year and Date: 2021-08-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of Kumaizasa (<i>Sasa senanensis</i>) Leaf Extract on Innate Immune Regulation in HEK293 Cells and Macrophages (2021)
  • Author(s): SATO KEISUKE、TATSUNAMI RYOSUKE、NAKATA AKIFUMI、KOMATSU KEN-ICHI、HARAKAWA SHINJI、NEDACHI TAKAKI、HAKETA KAORU、INAGAWA HIROYUKI、WAKAME KOJI
  • Journal Title: Anticancer Research Volume: 41 Issue: 8 Pages: 4093-4100
  • DOI: 10.21873/anticanres.15212
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of Global DNA Methylation and Gene Expression of Izumo1 and Izumo1r in Gonads after High- and Low-Dose Radiation in Neonatal Mice (2021)
  • Author(s): Nakata Akifumi、Sato Keisuke、Fujishima Yohei、Ting Valerie Goh Swee、Nakayama Kanade、Ariyoshi Kentaro、Tsuruoka Chizuru、Shang Yi、Iizuka Daisuke、Kakinuma Shizuko、Yamashiro Hideaki、Miura Tomisato
  • Journal Title: Biology Volume: 10 Issue: 12 Pages: 1270-1270
  • DOI: 10.3390/biology10121270
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Contribution of light and electron microscopy in the identification of morphological alterations in large Japanese field mouse (Apodemus speciosus) testes exposed to low-dose-rate radiations. (2021)
  • Author(s): Gatti, M., Palmerini, M. G., Belli, M., Nottola, S. A., Fujishima, Y., Yamashiro, H., Nakata, A., Miura, T., & Macchiarelli, G.
  • Journal Title: Microscopie Volume: 31 Pages: 1-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Morphological reproductive characteristics of testes and fertilization capacity of cryopreserved sperm after the Fukushima accident in raccoon ( Procyon lotor ) (2021)
  • Author(s): Komatsu Kazuki、Iwasaki Tsugumi、Murata Kosuke、Yamashiro Hideaki、Goh Valerie Swee Ting、Nakayama Ryo、Fujishima Yohei、Ono Takumi、Kino Yasushi、Simizu Yoshinaka、Takahashi Atsushi、Shinoda Hisashi、Ariyoshi Kentaro、Kasai Kosuke et al.
  • Journal Title: Reproduction in Domestic Animals Volume: 56 Issue: 3 Pages: 484-497
  • DOI: 10.1111/rda.13887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transition of Radioactive Cesium Deposition in Reproductive Organs of Free-Roaming Cats in Namie Town, Fukushima (2021)
  • Author(s): Fujishima Yohei、Kino Yasushi、Ono Takumi、Goh Valerie Swee Ting、Nakata Akifumi、Ariyoshi Kentaro、Kasai Kosuke、Toyoda Tadashi、Akama Toru、Tazoe Hirofumi、Yamada Masatoshi、Yoshida Mitsuaki A.、Miura Tomisato
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 18 Issue: 4 Pages: 1772-1772
  • DOI: 10.3390/ijerph18041772
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Seasonal changes in the spermatogenesis of the large Japanese field mice (Apodemus speciosus) controlled by proliferation and apoptosis of germ cells (2020)
  • Author(s): Ito Jun、Meguro Kanna、Komatsu Kazuki、Ohdaira Takuya、Shoji Rina、Yamada Takahisa、Sugimura Satoshi、Fujishima Yohei、Nakata Akifumi、Fukumoto Manabu、Miura Tomisato、Yamashiro Hideaki
  • Journal Title: Animal Reproduction Science Volume: 214 Pages: 106288-106288
  • DOI: 10.1016/j.anireprosci.2020.106288
  • Peer Reviewed
• [Journal Article] Environmental radiation on large Japanese field mice in Fukushima reduced colony forming potential in hematopoietic progenitor cells without inducing genomic instability. (2020)
  • Author(s): Ariyoshi, Tomisato Miura, Kosuke Kasai, Valerie Swee Ting Goh, Yohei Fujishima, Akifumi Nakata, Atsushi Takahashi, Yoshinaka Shimizu, Hisashi Shinoda, Hideaki Yamashiro, Colin Seymour, Carmel Mothersill & Mitsuaki A. Yoshida.
  • Journal Title: International Journal of Radiation Biology Volume: 96 Issue: 6 Pages: 1-12
  • DOI: 10.1080/09553002.2020.1807643
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improved harvest and fixation methodology for isolated human peripheral blood mononuclear cells in cytokinesis-block micronucleus assay (2020)
  • Author(s): Goh Valerie Swee Ting、Nakayama Ryo、Blakely William F.、Abe Yu、Chua Christelle En Lin、Chew Zi Huai、Nakata Akifumi、Fujishima Yohei、Yoshida Mitsuaki A.、Kasai Kosuke、Ariyoshi Kentaro、Miura Tomisato
  • Journal Title: International Journal of Radiation Biology Volume: 97 Issue: 2 Pages: 194-207
  • DOI: 10.1080/09553002.2021.1844338
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extracellular vesicles released from irradiated neonatal mouse cheek tissue increased cell survival after radiation (2020)
  • Author(s): Ariyoshi Kentaro、Hiroyama Yota、Fujiwara Naoya、Miura Tomisato、Kasai Kosuke、Nakata Akifumi、Fujishima Yohei、Ting Goh Valerie Swee、Yoshida Mitsuaki A
  • Journal Title: Journal of Radiation Research Volume: 62 Issue: 1 Pages: 73-78
  • DOI: 10.1093/jrr/rraa106
  • Peer Reviewed
• [Journal Article] Assessment of chromosome aberrations in large Japanese field mice (Apodemus speciosus) in Namie Town, Fukushima (2020)
  • Author(s): Fujishima Yohei、Nakata Akifumi、Ujiie Risa、Kasai Kosuke、Ariyoshi Kentaro、Goh Valerie Swee Ting、Suzuki Kojun、Tazoe Hirofumi、Yamada Masatoshi、Yoshida Mitsuaki A.、Miura Tomisato
  • Journal Title: International Journal of Radiation Biology Volume: - Issue: 6 Pages: 1-9
  • DOI: 10.1080/09553002.2020.1787548
  • Peer Reviewed
• [Presentation] Induction of Myc Overexpression and Genomic Instability in Artificial Human Aneuploid Cells (2022)
  • Author(s): Ariyoshi K, Fujishima Y, Kasai K, Miura T, Nakata A, Yoshida M
  • Organizer: 日本放射線影響学会第65回大会
• [Presentation] Development of a rapid C-banding method for dicentric chromosome aberration analysis in biodosimetry (2022)
  • Author(s): Takebayashi K, Sasaki N, Nakayama R, Fujishima Y, Goh VST, Anderson D, Yoshida MA, Nakata A, Miura T
  • Organizer: 日本放射線影響学会第65回大会
• [Presentation] Comprehensive exploration for germline-specific radiosensitive biomarkers in the testis of large Japanese field mice（Apodemus speciosus）after the Fukushima accident (2022)
  • Author(s): Tokita S, Annnaka K, Nakayama R, Fujishima Y, Goh VST, Nakata A, Fukumoto M, Miura T, Yamashiro H.
  • Organizer: 日本放射線影響学会第65回大会
• [Presentation] 非繁殖期の野生アカネズミにおける抗インヒビン血清とアクチビンBによる採卵数及び体外卵成熟率への影響 (2022)
  • Author(s): 浅香里枝子、安中健人、時田駿、茅原誠、中田章史、三浦富智、山城秀昭
  • Organizer: 第63回日本卵子学会学術集会
• [Presentation] Experiments to obtain source efficiency of skin contaminated with solution containing alpha emitters (2022)
  • Author(s): Kim E, Narita M, Takashima Y, Nakata A, Tani K, Kurihara O
  • Organizer: International Conference on Individual Monitoring of Ionising Radiation (IM2022) and Neutron and Ion Dosimetry Symposium (NEUDOS-14
  • Int'l Joint Research
• [Presentation] 季節的変化に伴う野生アカネズミ精原幹細胞の自己複製および分化に関わる遺伝子の網羅的発現解析 (2022)
  • Author(s): 時田駿、米倉詩菜、安中健人、長谷川千尋、中田章史、三浦富智、山城秀昭
  • Organizer: 第115回日本繁殖生物学会
• [Presentation] 福島の野生動物 -アカネズミとプラナリア- に対する低線量放射線影響の可能性 (2021)
  • Author(s): 有吉健太郎、藤嶋洋平、Valerie GOH Swee Ting、高橋温、清水良央、篠田壽、葛西宏介、中田章史、三浦富智、吉田光明
  • Organizer: 日本放射線影響学会第64回大会
• [Presentation] 福島県の放射線汚染地域に生息するニホンザルにおける染色体転座解析 (2021)
  • Author(s): 藤嶋洋平、鈴木正敏、Valerie GOH Swee Ting、有吉健太郎、葛西宏介、中田章史、木野康志、岡壽崇、篠田壽、清水良央、高橋温、鈴木敏彦、吉田光明、三浦富智
  • Organizer: 日本放射線影響学会第64回大会
• [Presentation] 季節繁殖性の野生アカネズミにおける精原幹細胞の動態 (2021)
  • Author(s): 時田駿、米倉詩菜、岩崎亜美、村田康輔、中田章史、三浦富智、山城秀昭
  • Organizer: 第114回日本繁殖生物学会大会
• [Presentation] Lipin1遺伝子を誘導する桑葉（Morus australis）粉末の肝細胞癌発生予防作用 (2021)
  • Author(s): 若命浩二、中田章史、佐藤恵亮、小松健一、河西正文
  • Organizer: 第25回バイオ治療法研究会
• [Presentation] 福島県浪江町に生息する野生動物の臓器の放射性セシウム濃度測定と内部被ばく線量推定 (2020)
  • Author(s): 小野拓実、木野康志、高橋温、鈴木敏彦、清水良央、千葉美麗、藤嶋洋平、Valerie GOH、有吉健太郎、中田章史、鈴木正敏、山城秀昭、関根勉、篠田壽、三浦富智
  • Organizer: 日本放射線影響学会第63回大会
• [Presentation] 歯は個体被ばく量を評価するうえで有用である (2020)
  • Author(s): 高橋温、小野巧実、小荒井一真、岡壽崇、清水良央、千葉美麗、鈴木俊彦、有吉健太郎、葛西宏介、中田章史、藤嶋洋平、山城秀昭、関根勉、佐々木啓一、木野康志、三浦富智、篠田壽
  • Organizer: 日本放射線影響学会第63回大会
• [Presentation] 福島県の放射線汚染地域に生息する種々の野生動物における染色体解析 (2020)
  • Author(s): 藤嶋洋平、中田章史、Valerie GOH、葛西宏介、有吉健太郎、鈴樹亨純、山城秀昭、篠田壽、吉田光明、三浦富智
  • Organizer: 日本放射線影響学会第63回大会
• [Presentation] 被災アライグマにおける生殖機能への影響評価 (2020)
  • Author(s): 岩崎亜美、村田康輔、山城秀昭、Valerie GOH、中山亮、藤嶋洋平、小野巧実、木野康志、清水良央、高橋温、篠田壽、有吉健太郎、葛西宏介、鈴木正敏、福本学、吉田光明、中田章史、三浦富智
  • Organizer: 日本放射線影響学会第63回大会
• [Presentation] 放射線によるマウス生殖系列細胞の影響解析 (2020)
  • Author(s): 中田章史、坂本菜子、岡田栞奈、上田政二、五十嵐萌、江川祥子、飯塚大輔、鶴岡千鶴、尚奕、柿沼志津子、阿部靖之、山城秀昭、吉田光明、三浦富智
  • Organizer: 日本放射線影響学会第63回大会
• [Presentation] 被災アカネズミの保存凍結精子を用いた受精能評価 (2020)
  • Author(s): 二瓶和、 時田駿、村田康輔、岩崎亜美、山城秀昭、中田章史、藤嶋洋平、三浦富智
  • Organizer: 日本放射線影響学会第63回大会