Research on the mechanisms for radioadaptive response

• Project/Area Number: 25340041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Nenoi Mitsuru 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 人材育成センター, センター長(定常) (10164659)
• Co-Investigator(Kenkyū-buntansha): 王 冰 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線影響研究部, チームリーダー(定常) (10300914) ; 塚本 智史 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 技術安全部, 主任研究員(定常) (80510693)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 放射線適応応答 / マウス胎児 / 発生異常 / 系統差 / 受精卵移植 / 母体内因子

Outline of Final Research Achievements

When the pregnant mice of ICR strain and C57BL strain are exposed to low dose radiation, the fetuses transiently acquire a resistance against the following high dose radiation in regards to the frequency of malformation occurrence. In order to reveal the mechanisms for this so-called radioadaptive response (RAR), in vitro-fertilized eggs from donors of RAR-proficient mouse strains (ICR or C57BL) were transplanted into the recipient (surrogate) mothers of RAR-deficient strain (C3H), and induction of RAR in the fetuses was tested. Induction of RAR in the fetuses obtained from the reversed strain combination of the donor and the recipient was also tested. As a result, we revealed that the strain-dependent RAR factor existed in the body of the recipient mother mice, and that EGF and bFGF are the components of responsible maternal factors for the strain-dependent RAR.

Research Products

• [Journal Article] Differences in sustained alterations in protein expression between livers of mice exposed to high-dose and low-dose rate radiation. (2017)
  • Author(s): Tetsuo Nakajima, Bing Wang, Tetsuya Ono, Yoshihiko Uehara, Shingo Nakamura, Kazuaki Ichinohe, Ignacia Braga-Tanaka III, Satoshi Tanaka, Kimio Tanaka, Mitsuru Nenoi
  • Journal Title: Journal of Radiation Research Volume: 印刷中 Issue: 4 Pages: 421-429
  • DOI: 10.1093/jrr/rrw133
  • Peer Reviewed / Open Access
• [Journal Article] NCRP解説書24「低線量放射線の健康影響：放射線生物学・疫学の統合の展望」 (2017)
  • Author(s): 今岡達彦, 勝部孝則, 川口勇生, 臺野和広, 土居主尚, 中島徹夫, 森岡孝満, 山田裕, 王冰, 神田玲子, 西村まゆみ, 二宮康晴, 村上正弘, 吉永信治, 柿沼志津子
  • Journal Title: 保健物理 Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver. (2016)
  • Author(s): Tetsuo Nakajima, Guillaume Vares, Bing Wang, Mitsuru Nenoi
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146730-e0146730
  • DOI: 10.1371/journal.pone.0146730
  • Peer Reviewed / Open Access
• [Journal Article] Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice. (2015)
  • Author(s): Bing Wang, Kaoru Tanaka, Takanori Katsube, Yasuharu Ninomiya, Guillaume Vares, Qiang Liu, Akinori Morita, Tetsuo Nakajima, Mitsuru Nenoi
  • Journal Title: Journal of Radiation Research Volume: 56 Issue: 5 Pages: 760-767
  • DOI: 10.1093/jrr/rrv030
  • NAID: 120006959730
  • Peer Reviewed / Open Access
• [Journal Article] Carbon ion beam combined with cisplatin effectively disrupts triple negative breast cancer stem-like cells in vitro. (2015)
  • Author(s): Sei Sai, Guillaume Vares, Eun Ho Kim, Kumiko Karasawa, Bing Wang, Mitsuru Nenoi, Yoshiya Horimoto, Mitsuhiro Hayashi
  • Journal Title: Molecular Cancer Volume: 14 Issue: 1 Pages: 1-13
  • DOI: 10.1186/s12943-015-0429-7
  • Peer Reviewed / Open Access
• [Journal Article] Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells (2015)
  • Author(s): Vares G, Sai S, Wang B, Fujimori A, Nenoi M, Nakajima T.
  • Journal Title: Cancer Letter Volume: 362 Issue: 2 Pages: 167-173
  • DOI: 10.1016/j.canlet.2015.03.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In vivo radioadaptive response: a review of studies relevant to radiation-induced cancer risk. (2015)
  • Author(s): Nenoi,M., Wang,B., Vares,G
  • Journal Title: Human and Experimental Toxicology Volume: 34 Issue: 3 Pages: 272-283
  • DOI: 10.1177/0960327114537537
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells. (2014)
  • Author(s): Ninomiya Y, Cui X, Yasuda T, Wang B, Yu D, Sekine-Suzuki E, Nenoi M
  • Journal Title: BMB Rep Volume: 47 Pages: 575-580
  • Peer Reviewed / Open Access
• [Journal Article] Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR and is not dependent on DNA double-strand breaks. (2014)
  • Author(s): Katsube T, Mori M, Tsuji H, Shiomi T, Wang B, Liu Q, Nenoi M, Onoda M
  • Journal Title: J Biochem Volume: 156 Pages: 85-95
  • Peer Reviewed
• [Journal Article] AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation. (2014)
  • Author(s): A. Morita, S. Ariyasu, B. Wang, T. Asanuma, T. Onoda, A. Sawa, K. Tanaka, I. Takahashi, S. Togami, M. Nenoi, T. Inaba and S. Aoki.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 450 Issue: 4 Pages: 1498-1504
  • DOI: 10.1016/j.bbrc.2014.07.037
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diet-Induced Obesity Modulates Epigenetic Responses to Ionizing Radiation in Mice. (2014)
  • Author(s): Vares G, Wang B, Ishii-Ohba H, Nenoi M, Nakajima T
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e106277-e106277
  • DOI: 10.1371/journal.pone.0106277
  • Peer Reviewed / Open Access
• [Journal Article] 活性酸素種と抗酸化能の観点からの放射線適応応答の考察 (2014)
  • Author(s): 二宮康晴、王冰、根井充
  • Journal Title: Radiation Biology Research Communications Volume: 49 Pages: 396-409
  • NAID: 40020314335
  • Peer Reviewed
• [Journal Article] 低線量放射線被ばくと認知症発症―マウスモデルでの検証― (2014)
  • Author(s): 田中薫、季斌、王冰、根井充
  • Journal Title: Isotope News Volume: 726 Pages: 25-27
• [Journal Article] Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice (2014)
  • Author(s): Wang B, Tanaka K, Ji B, Ono M, Fang Y, Ninomiya Y, Maruyama K, Izumi-Nakajima N, Begum N, Higuchi M, Fujimori A, Uehara Y, Nakajima T, Suhara T, Ono T, Nenoi M
  • Journal Title: J Radiat Res Volume: 55 Issue: 1 Pages: 84-96
  • DOI: 10.1093/jrr/rrt096
  • Peer Reviewed
• [Journal Article] Low-Dose Total Body Carbon-Ion Irradiations Induce Early Transcriptional Alteration without Late Alzheimer’s Disease-Like Pathogenesis and Memory Impairment in Mice. (2014)
  • Author(s): Bing Wang, Kaoru Tanaka, Bin Ji, Maiko Ono, Yaqun Fang, Yasuharu Ninomiya, Kouichi Maruyama, Nakako Izumi-Nakajima, Nasrin Begum, Makoto Higuchi, Akira Fujimori, Yoshihiko Uehara, Tetsuo Nakajima, Testuya Suhara, Mitsuru Nenoi.
  • Journal Title: Journal of Neuroscience Research Volume: 92 Issue: 7 Pages: 915-926
  • DOI: 10.1002/jnr.23363
  • Peer Reviewed
• [Journal Article] Sodium orthovanadate (vanadate), a potent mitigator of radiation-induced damage to the hematopoietic system in mice (2013)
  • Author(s): Wang B, Tanaka K, Morita A, Ninomiya Y, Maruyama K, Fujita K, Hosoi Y, Nenoi M
  • Journal Title: J. Radiat. Res Volume: 54 Issue: 4 Pages: 620-629
  • DOI: 10.1093/jrr/rrs140
  • Peer Reviewed
• [Journal Article] 放射線感受性個人差要因の解明とリスク低減化を目指して。 (2013)
  • Author(s): 根井充、中島徹夫、王冰、石井洋子、Guillaume Vares、勝部孝則、二宮康晴、田中薫、小池亜紀、小池学
  • Journal Title: 放射線科学 Volume: 56 Pages: 4-17
  • Peer Reviewed
• [Presentation] XRCC4 and Artemis participate in the DNA damage response to heavy ion-beams in human cells. (2016)
  • Author(s): 勝部孝則, Qiang Liu, 王冰, Yi Xie, 二宮康晴, 根井充
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 神奈川県、横浜市
  • Year and Date: 2016-11-30
• [Presentation] 低線量或は高線量X線被ばく後のマウス肝臓におけるメタボローム解析 (2016)
  • Author(s): 中島徹夫, Guillaume Varès, 二宮康晴, 王冰, 勝部孝則, 田中薫, 劉翠華, 平川博一, 丸山耕一, 藤森亮, 根井充
  • Organizer: 第54回日本生物物理学会年会
  • Place of Presentation: 茨城県、つくば市
  • Year and Date: 2016-11-25
• [Presentation] p53標的創薬研究から得られたp53転写調節剤5-クロロ-8-キノリノールの放射線防護作用機構解析 (2016)
  • Author(s): 森田明典, 高橋一平, 笹谷めぐみ, 青木伸, 王冰, 有安真也, 田中薫, 澤晶子,西友里恵, 寺岡達郎, 氏田将平, 谷本圭司, 根井充, 神谷研二, 永田靖, 細井義夫, 稲葉俊哉
  • Organizer: 第59回日本放射線影響学会大会
  • Place of Presentation: 広島県、広島市
  • Year and Date: 2016-10-26
• [Presentation] GFPトランスジェニックマウスの骨髄における放射線感受性に関する解析 (2016)
  • Author(s): 二宮康晴, 田中薫, 根井充, 王冰
  • Organizer: 第59回日本放射線影響学会大会
  • Place of Presentation: 広島県、広島市
  • Year and Date: 2016-10-26
• [Presentation] 日本酒（純米酒、純米吟醸酒）摂取の肝臓代謝への影響と放射線影響修飾効果 (2016)
  • Author(s): 中島徹夫, Guillaume Varès, 王冰, 根井充
  • Organizer: 第70回日本栄養・食糧学会
  • Place of Presentation: 兵庫県、神戸市
  • Year and Date: 2016-05-13
• [Presentation] Effects from chronic restraint-induced stress and total body irradiation on the hematopoietic system in mice. (2015)
  • Author(s): Bing Wang, Kaoru Tanaka, Takanori Katsube, Yasuharu Ninomiya, Guillaume Vares, Qiang Liu, Akinori Morita, Tetsuo Nakajima, and Mitsuru Nenoi
  • Organizer: The 61st Annual Meeting of the Radiation Research Society
  • Place of Presentation: Weston, Florida, USA
  • Year and Date: 2015-09-19
• [Presentation] Effects from chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes. (2015)
  • Author(s): Takanori Katsube, Bing Wang, Kaoru Tanaka, Yasuharu Ninomiya, Guillaume Vares, Qiang Liu, Akinori Morita, Tetsuo Nakajima, and Mitsuru Nenoi
  • Organizer: The 61st Annual Meeting of the Radiation Research Society
  • Place of Presentation: Weston, Florida, USA
  • Year and Date: 2015-09-19
• [Presentation] Radio-sensitivity Modifying Factors (2015)
  • Author(s): Mitsuru Nenoi, Bing Wang, Tetsuo Nakajima, Akira Fujimori, Guillaume Vares, Takanori Katsube, Yasuharu Ninomiya, Kaoru Tanaka, Cuihua Liu
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Reduction of High-dose-radiation-induced Delayed Genotoxic Effects by Radioadaptive Response and Mild Diet Restriction in Mice. (2015)
  • Author(s): Bing Wang, Kaoru Tanaka, Yasuharu Ninomiya, Takanori Katsube, Kouichi Maruyama, Guillaume Vares, Kiyomi Eguchi Kasai, Mitsuru Nenoi
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] A Comparative Study of Mediation of Chronic Drinking of Two Kinds of Japanese Sake on Radiation-induced Metabolic Alteration. (2015)
  • Author(s): Tetsuo Nakajima, Guillaume Vares, Bing Wang, Mitsuru Nenoi
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Study on Heavy-ion-irradiation-induced Adaptive Response in Mice. (2015)
  • Author(s): Kaoru Tanaka, Bing Wang, Yasuhara Ninomiya, Kouichi Maruyama, Guillaume Vares, Kazuko Fujita, Kiyomi Eguchi Kasai, Mitsuru Nenoi
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25
• [Presentation] Histone H2AX Phosphorylation After Hydrogen Peroxide Treatment Is Mediated By ATR and Not Depending on DNA Double-strand Breaks. (2015)
  • Author(s): Takanori Katsube, Masahiko Mori, Hideo Tsuji, Tadashi Shiomi, Bing Wang, Qiang Liu, Mitsuru Nenoi, Makoto Onoda
  • Organizer: International Congress of Radiation Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] A potent mitigator of radiation-induced damage to the hematopoietic system in mice. (2014)
  • Author(s): Mitsuru Nenoi, Bing Wang, Kaoru Tanaka, Akinori Morita
  • Organizer: The 7th National Congress of Radiation Medicine and Protection
  • Place of Presentation: 重慶（中国）
  • Year and Date: 2014-10-16 – 2014-10-17
  • Invited
• [Presentation] 日本酒の継続的摂取が放射線影響に与える修飾効果について (2014)
  • Author(s): 中島徹夫、Guillaume Vares、王冰、石井洋子、根井充
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] 低線量率放射線長期被ばく下での放射線抵抗性獲得に関する考察 (2014)
  • Author(s): 根井充、王冰、Guillaume Vares
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] Obesity-related Modulation of Radiation Responses in the Mouse Liver: the Role of miRNAs. (2014)
  • Author(s): Vares,G., Nakajima,T., Wang,B., Ishii,H., Nenoi,M
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] 重粒子線誘発マウス適応応答の機構研究(予備的研究) (2014)
  • Author(s): 田中薫、王冰、二宮康晴、丸山耕一、ヴァレス・ギヨーム、藤田和子、笠井清美、根井充
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] GFPトランスジェニックマウスの放射線感受性の解析 (2014)
  • Author(s): 二宮康晴、田中薫、王冰、石井洋子、根井充
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] FISH法による身体拘束ストレスの放射線感受性修飾作用に関する解析 (2014)
  • Author(s): 勝部孝則、田中薫、王冰、二宮康晴、ヴァレス ギョーム、劉強、森田明典、中島徹夫、根井充
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] 8-キノリノール誘導体AS-2のp53依存性アポトーシス抑制機構 (2014)
  • Author(s): 浅沼哲雄、森田明典、小野田貴祥、有安真也、王冰、澤晶子、田中薫、高橋一平、根井充、稲葉俊哉、青木伸
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] 新規放射線防護剤候補化合物の活性評価 (2014)
  • Author(s): 小野田貴祥、森田明典、浅沼哲雄、有安真也、澤晶子、王冰、田中薫、根井充、青木伸
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] Transcription factors potentially involved in gene regulation after long-term, low dose-rate irradiation. (2013)
  • Author(s): Mitsuru Nenoi, Guillaume Vares, Yoshihiko Uehara, Tetsuya Ono, Tetsuo Nakajima, Bing Wang, Keiko Taki, Tsuneya Matsumoto, Yoichi Oghiso, Kimio Tanaka, Kazuaki Ichinohe, Shingo Nakamura, Satoshi Tanaka
  • Organizer: The 3rd Asian Congress of Radiation research
  • Place of Presentation: Beijing
• [Presentation] Failed verification of Alzheimer’s desease-like alterations in mouse brain after exposure to low dose radiation. (2013)
  • Author(s): Wang,B., Tanaka,K., Ji,B., Ono,M., Fang,Y., Ninomiya,Y., Maruyama,K., Nakajima,N., Begum,N., Higuchi,N., Fujimori,A., Uehara,Y., Nakajima,T., Suhara,T., Ono,T., Nenoi,M.
  • Organizer: The 3rd Asian Congress of Radiation Research
  • Place of Presentation: Beijing
  • Invited
• [Presentation] Induction of adaptive response (Yonezawa Effect) by combination of irradiations with different LET values in mice. (2013)
  • Author(s): Tanaka,K., Wang,B., Ninomiya,Y., Maruyama,K., Vares,G., Morimoto,Y., Fujita,K., Eguchi-Kasai,K., Nenoi,M
  • Organizer: The 3rd Asian Congress of Radiation Research
  • Place of Presentation: Beijing
• [Presentation] 胎児・成体マウスにおける放射線誘発適応応答は重粒子線にも当て嵌まるか? VI.成体マウスを用いた実験結果のまとめ(PartII)。 (2013)
  • Author(s): 田中薫、王冰、二宮康晴、丸山耕一、ヴァレス・ギヨーム、藤田和子、笠井清美、根井充
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
• [Book] Dietary Modification of Mouse Response to Total-Body-Irradiation. In “Evolution of Ionizing Radiation Research” (ed. Mitsuru Nenoi) (2015)
  • Author(s): Wang B, Tanaka K, Katsube T, Maruyama K, Ninomiya Y, Nenoi M
  • Publisher: In Tech (Rijeka, Croatia)
• [Book] Evolution of Ionizing Radiation Research (2015)
  • Author(s): Mitsuru Nenoi (エディター)
  • Total Pages: 306
  • Publisher: In Tech (Rijeka, Croatia)
• [Remarks] 国立研究開発法人量子科学技術研究開発機構放射線医学総合研究所
  • URL: http://www.nirs.go.jp/index.shtml
• [Remarks] 国立研究開発法人量子科学技術研究開発機構
  • URL: http://www.qst.go.jp/