Advanced research on the biological effects of genotoxic stress using different irradiation conditions and induced pluripotent cells

• Project/Area Number: 25340033
• 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: Hiroshima University
• Principal Investigator: KAWAI HIDEHIKO 広島大学, 原爆放射線医科学研究所, 助教 (30379846)
• Co-Investigator(Kenkyū-buntansha): SHIMAMOTO AKIRA 広島大学, 大学院医歯薬保健学研究院(薬), 准教授 (70432713)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 放射線照射条件 / iPS細胞 / 放射線 / 急照射 / 緩照射 / ゲノム安定性 / ゲノム編集

Outline of Final Research Achievements

In order to uncover the underlying mechanisms of genotoxic stress-induced biological effects, we have analyzed the cellular and molecular responses to various types of genotoxic stress in various types of cultured cell lines, including human induced pluripotent stem (hiPS) cells and p53-mutated iPS cells. As a result, we have found that iPS cells maintain their genomic stability thorough both p53-depnendent and -independent apoptotic pathways. These results provide important clues to the understanding of the mechanisms of maintaining genomic stability in multi-potent or tissue stem cells, and the improvement of the quality control of those cells.

Research Products

• [Journal Article] Mitochondrial reactive oxygen species perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of PP2A in low-dose irradiated human fibroblasts. (2016)
  • Author(s): Shimura T, Sasatani M, Kamiya K, Kawai H, Inaba Y, Kunugita N.
  • Journal Title: Oncotarget Volume: 7 Issue: 3 Pages: 3559-70
  • DOI: 10.18632/oncotarget.6518
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hepcidin-2 in mouse urine as a candidate radiation-responsive molecule. (2016)
  • Author(s): Iizuka D, Yoshioka S, Kawai H, Okazaki E, Kiriyama K, Izumi S, Nishimura M, Shimada Y, Kamiya K, Suzuki F.
  • Journal Title: J Radiat Res Volume: 57(2) Issue: 2 Pages: 142-149
  • DOI: 10.1093/jrr/rrv098
  • Peer Reviewed / Open Access
• [Journal Article] A novel ATM/TP53/p21-mediated checkpoint only activated by chronic γ-irradiation (2014)
  • Author(s): CAO Lili, KAWAI Hidehiko, SASATANI Megumi, IIZUKA Daisuke, MASUDA Yuji, INABA Toshiya, SUZUKI Keiji, OOTSUYAMA Akira, UMATA Toshiyuki, KAMIYA Kenji, SUZUKI Fumio
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e104279-e104279
  • DOI: 10.1371/journal.pone.0104279
  • NAID: 120006986457
  • Peer Reviewed / Open Access
• [Journal Article] Selective enhancing effect of Early mitotic inhibitor 1 depletion on sensi tivity of doxorubicin. (2013)
  • Author(s): Shimizu N, Nakajima NI, Tsunematsu T, Ogawa I, Kawai H, Hirayama R, Fujimori A, Yamada A, Okayasu R, Ishimaru N, Takata T, Kudo Y.
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 24 Pages: 17238-17252
  • DOI: 10.1074/jbc.m112.446351
  • Peer Reviewed
• [Presentation] ハイスループット解析技術による放射線照射環境下での細胞応答の研究 (2015)
  • Author(s): 河合秀彦，曹麗麗，金井昭教，稲葉俊哉，神谷研二，鈴木文男
  • Organizer: 第１回放射線ワークショップ
  • Place of Presentation: 富山市
  • Year and Date: 2015-10-16
• [Presentation] 放射線照射環境での細胞応答の解析 (2015)
  • Author(s): 河合秀彦
  • Organizer: 変異機構研究会第２８回夏の学校
  • Place of Presentation: 小牧市
  • Year and Date: 2015-07-25
  • Invited
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2015)
  • Author(s): 金井昭教，長町安希子，河合秀彦，松井啓隆，神谷研二，稲葉俊哉
  • Organizer: 第４０回中国地区放射線影響研究会
  • Place of Presentation: 東広島市
  • Year and Date: 2015-07-17
• [Presentation] 放射線によるDNA損傷シグナル活性化におけるRAD18の寄与 (2015)
  • Author(s): 笹谷めぐみ，徐衍賓，河合秀彦，飯塚大輔，神谷研二
  • Organizer: 第５６回原子爆弾後障害研究会
  • Place of Presentation: 広島市
  • Year and Date: 2015-06-07
• [Presentation] γ線照射環境での細胞運命決定とその制御因子の同定 (2015)
  • Author(s): 曹麗麗，河合秀彦，稲葉俊哉，鈴木文男，神谷研二
  • Organizer: 第５６回原子爆弾後障害研究会
  • Place of Presentation: 広島市
  • Year and Date: 2015-06-07
• [Presentation] 低線量（率）放射線がマウス着床前期胚発生過程に与える影響 (2015)
  • Author(s): 清水なつみ，河合秀彦，笹谷めぐみ，遠藤充浩，稲葉俊哉，神谷研二
  • Organizer: 第５６回原子爆弾後障害研究会
  • Place of Presentation: 広島市
  • Year and Date: 2015-06-07
• [Presentation] An Integrated Approach Using High-throughput Sequencing and Imaging Technologies to the Study of Cellular Responses to Low Dose Radiation (2015)
  • Author(s): Kawai H, Cao L, Shimizu N, Matsui H, Kanai A, Hirouchi T, Inaba T, Kamiya K, Suzuki F.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Differential Response to Acute and Chronic Low Dose Gamma Irradiation in Primary Human Endothelial Cells (2015)
  • Author(s): Zaharieva E, Kawai H, Inaba T, Matsuura S, Kamiya K.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] The Effect of Low Dose Radiation on The Development of Early Mouse Embryos (2015)
  • Author(s): Shimizu N, Kawai H, Sasatani M, Endoh M, Inaba T, Kamiya K.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] DNA Damage Response in Human Induced Pluripotent Stem Cells (2015)
  • Author(s): Shimamoto A, Kagawa H, Kawai H, Sakuma T, Yamamoto T, Shiotani B, Tahara H.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Enhanced DNA End Resection and Subsequent Responses During The Processing of Complex DNA Double Strand Breaks Induced By Heavy Ion Beams (2015)
  • Author(s): Yajima H, Liu C, Xue L, Fujisawa H, Nakajima N, Kawai H.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] RAD18 Activates The G2/M Checkpoint Through DNA Damage Signaling to Maintain Genome Integrity By Ionizing Radiation (2015)
  • Author(s): Sasatani M, Xu Y, Kawai H, Cao L, Tateishi S, Li J, Iizuka D, Kamiya K.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Novel Mechanism of Human PCNA Ubiquitination Mediated by Two E2- E3 Pairs (2015)
  • Author(s): Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, Masutani C, Hishida T, Suzuki F, Kamiya K.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] The function of Chromatin Remodeling Complexes in Cell-fate Decision in Response to Chronic Ionizing Irradiation (2015)
  • Author(s): Cao L, Kawai H, Inaba T, Suzuki F, Kamiya K.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Analysis of Radiation Induced Mutations Using Next Generation Sequencer (2015)
  • Author(s): Kanai A, Nagamachi A, Kawai H, Matsui H, Kamiya K, Inaba T.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto, JAPAN
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Comprehensive analyses of cellular responses to chronic γ-irradiation (II) (2015)
  • Author(s): 河合秀彦、曹麗麗、清水なつみ、笹谷めぐみ、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] Analysis of radiation induced mutations using next generation sequencer (2015)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、神谷研二、稲葉俊哉
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] Effects of low dose gamma irradiation on primary human endothelial cells (2015)
  • Author(s): Elena Zaharieva、河合秀彦、稲葉俊哉、松浦伸也、神谷研二
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] The effect low dose radiation exposure in the first hours after fertilization on the development of early mouse embryos (2015)
  • Author(s): 清水なつみ、河合秀彦、笹谷めぐみ、遠藤充浩、稲葉俊哉、神谷研二
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] DNA Damage Response in Human Induced Pluripotent Stem Cells (2015)
  • Author(s): 嶋本顕、香川晴信、河合秀彦、佐久間哲史、山本卓、塩谷文章、田原栄俊
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] Perturbation of AKT/cyclin D1 signaling pathway by oxidative stresses following low dose long-term fractionated radiation in human human fibroblasts (2015)
  • Author(s): 志村勉、笹谷めぐみ、神谷研二、河合秀彦、 欅田尚樹
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] Dose rate-dependent cellular senescence in response to chronic γ-irradiation via the ATM/TP53/p21 pathway (2015)
  • Author(s): 曹麗麗、河合秀彦、笹谷めぐみ、飯塚大輔、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 広島大学原爆放射線医科学研究所第５回国際シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-03
• [Presentation] 異なる線量率での放射線被曝環境と細胞運命決定機構 (2014)
  • Author(s): 河合秀彦、曹麗麗、笹谷めぐみ、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-02
  • Invited
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2014)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、稲葉俊哉
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-02
• [Presentation] γ線照射環境での線量率依存的な老化様細胞増殖停止はATM/TP53/P21経路依存的である (2014)
  • Author(s): 曹麗麗、河合秀彦、笹谷めぐみ、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-02
• [Presentation] RAD18 mediates DNA damage signaling to activate G2/M checkpoint for maintaining genome integrity after ionizing radiation exposure (2014)
  • Author(s): 徐衍賓、笹谷めぐみ、河合秀彦、曹麗麗、飯塚大輔、神谷研二
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-02
• [Presentation] 大量データ解析を駆使した放射線影響解析手法の確立にむけて (2014)
  • Author(s): 松井啓隆、河合秀彦、金井昭教、稲葉俊哉
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-01
• [Presentation] 人工多能性幹細胞（iPS 細胞）のX 線高感受性の分子機構 (2014)
  • Author(s): 嶋本顕、香川晴信、河合秀彦、佐久間哲史、山本卓、塩谷文章、田原栄俊
  • Organizer: 日本放射線影響学会 第57回大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-01
• [Presentation] 放射線照射環境における線量率に依存した細胞運命決定機構の解析 (2014)
  • Author(s): 河合秀彦、曹麗麗、清水なつみ、笹谷めぐみ、飯塚大輔、金井昭教、松井啓隆、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 第39回 中国地区放射線影響研究会
  • Place of Presentation: 広島市
  • Year and Date: 2014-07-18
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析にむけた方法論の確立 (2014)
  • Author(s): 金井昭教、松井啓隆、長町安希子、河合秀彦、稲葉俊哉
  • Organizer: 第39回 中国地区放射線影響研究会
  • Place of Presentation: 広島市
  • Year and Date: 2014-07-18
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2014)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、稲葉俊哉
  • Organizer: 第55回原子爆弾後障害研究会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-06-01
• [Presentation] γ線照射環境下での線量率依存的な細胞運命決定とその分子機構の解析 (2014)
  • Author(s): 曹麗麗、河合秀彦、笹谷めぐみ、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 第55回原子爆弾後障害研究会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-06-01
• [Presentation] 糖鎖修飾を指標とした放射線被ばくのバイオマーカー探索 (2014)
  • Author(s): 飯塚大輔、桐山慧大、岡崎恵美、河合秀彦、泉俊輔、神谷研二
  • Organizer: 第55回原子爆弾後障害研究会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-06-01
• [Presentation] Ｅ３ユビキチンライゲースRAD18が放射線損傷応答におよぼす寄与 (2014)
  • Author(s): 徐衍賓、笹谷めぐみ、河合秀彦、飯塚大輔、神谷研二
  • Organizer: 第55回原子爆弾後障害研究会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-06-01
• [Presentation] A combination of experimental and bioinformatics approaches for assessing the biological effects of ionizing radiation (2014)
  • Author(s): 河合秀彦、曹麗麗、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、笹谷めぐみ、神谷研二、鈴木文男
  • Organizer: 広島大学原爆放射線医科学研究所・第４回国際シンポジウム
  • Place of Presentation: 広島市
• [Presentation] iPS cells show hypersensitivity to X-irradiation than isogenic somatic cells, leading to p53-depedent apoptosis (2014)
  • Author(s): 香川晴信、河合秀彦、佐久間哲史、山本卓、嶋本顕、田原 栄俊
  • Organizer: 広島大学原爆放射線医科学研究所・第４回国際シンポジウム
  • Place of Presentation: 広島市
• [Presentation] DOSE-RATE-DEPENDENT CELLULAR RESPONSES TO CHRONIC γ-IRRADIATION (2013)
  • Author(s): 曹麗麗、河合秀彦、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、笹谷めぐみ、神谷研二、鈴木文男
  • Organizer: THE 3rd ASIAN CONGRESS OF RADIATION RESEARCH
  • Place of Presentation: 北京 中国
• [Presentation] γ線照射環境下における細胞応答の線量率依存性の解析 (2013)
  • Author(s): 河合秀彦、曹麗麗、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、笹谷めぐみ、神谷研二、鈴木文男
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2013)
  • Author(s): 金井昭教、長町安希子 、河合秀彦、松井 啓隆、稲葉 俊哉
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
• [Presentation] 人工多能性幹細胞における X 線に対する高感受性細胞死の p53 依存的な誘導機構の解明 (2013)
  • Author(s): 香川晴信、河合秀彦、佐久間哲史、山本卓、塩谷文章、嶋本顕、田原 栄俊
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸市
• [Presentation] 恒常的な放射線被曝環境下のゲノム安定性維持にはATM-p53-p21経路の活性化が必要である
  • Author(s): 曹麗麗、河合秀彦、笹谷めぐみ、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、神谷研二、鈴木文男
  • Organizer: 第54回原子爆弾後障害研究会
  • Place of Presentation: 広島市
• [Presentation] 低線量率放射線被曝生体影響の細胞生物学的研究
  • Author(s): 河合秀彦
  • Organizer: 第54回原子爆弾後障害研究会
  • Place of Presentation: 広島市
  • Invited
• [Presentation] 放射線照射環境下での細胞応答とその分子機構
  • Author(s): 河合秀彦、曹麗麗、飯塚大輔、松井啓隆、金井昭教、稲葉俊哉、笹谷めぐみ、神谷研二、鈴木文男
  • Organizer: 第38回中国地区放射線影響研究会
  • Place of Presentation: 広島市