Radiation-induced long-lived radicals causing mutation and carcinogenesis

2008 Fiscal Year Final Research Report

• Project/Area Number: 16101002
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Masami Kyoto University, 原子炉実験所, 教授 (20111768)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Keiji 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (00196809) ; KODAMA Seiji 大阪府立大学, 産学官連携機構, 教授 (00195744) ; KUMAGAI Jun 名古屋大学, 大学院・工学研究科, 准教授 (20303662) ; SHIMADA Yoshiya 放射線医学総合研究所, プロジェクトリーダー (10201550)
• Project Period (FY): 2004 – 2008
• Keywords: 放射線 / 突然変異 / 細胞がん化 / 長寿命ラジカル

Research Abstract

放射線を照射された細胞に複数の長寿命ラジカル(LLR^*)が誘導されることがわかった。その代表的なものが、システイン残基を持つタンパク質に生じたスルフィニルラジカル(R-CH2-SO・)およびセミキセノンラジカルである。これらは、放射線被ばく後、1時間~10時間の間にミトコンドリアで誘導され、細胞内の高分子タンパクをゆっくりラジカル化することによって、細胞の様々な高度機能障害を生じさせることが明らかとなった。

Research Products

• [Journal Article] Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene (2009)
  • Author(s): Ariyoshi K, Suzuki K, Goto M, Oshimura M, Ishizaki K, Watanabe M, Kodama S
  • Journal Title: J. Radiat. Res. (in press)
• [Journal Article] Evaluation of the potential of hexamethylenetetramineas a combined agent with gamma-ray irradiation and cisplatin treatment in vivo, compared with tirapazamine (2009)
  • Author(s): Masunaga S, Tano K, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Ono K, Nakamura J
  • Journal Title: British J Radiol Jan 19(Epub ahead of print)
• [Journal Article] Induction of DNA double-strand breaks and cellular migration through bystander effects in cells irradiated with the slit-type microplanar beam of the SPring-8 synchrotron (2009)
  • Author(s): Kashino G, Kondoh T, Nariyama N, Umetani K, Ohigashi T, Shinohara K, Kurihara A, Fukumoto M, Tanaka H, Maruhashi A, Suzuki S, Kinashi Y, Liu Yong, Masunaga S,Watanabe M, Ono K
  • Journal Title: Intern J Radiat Oncol Biol Phys (in press)
• [Journal Article] Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells (2009)
  • Author(s): Masunaga S, Kono K, Nakamura J, Tano K, Yoshida Y, Watanabe M, Kashino G, Suzuki M, Kinashi Y, and Ono K
  • Journal Title: Oncology Report 21 Pages: 1307-1312
• [Journal Article] The contribution of radiation-induced large deletion of the genome to chromosomal instability (2009)
  • Author(s): Toyokuni H, Maruo A, Suzuki K, Watanabe M
  • Journal Title: Radiat Res 171 Pages: 198-203
• [Journal Article] Intervention of oxygen-control ability to radiation sensitivity, cell aging and cell transformation (2009)
  • Author(s): Yoshii H, Watanabe M
  • Journal Title: J RadiatRes (Tokyo) 50 Pages: 127-137
• [Journal Article] Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities (2009)
  • Author(s): Yoshikawa T, Kashino G, Ono K, Watanabe M
  • Journal Title: J Radiat Res(Tokyo) 50 Pages: 151-160
• [Journal Article] Establishment of ponasterone A-inducible the wild-type p53 protein-expressing clones from HSC-1 cells, cell growth suppression by p53 expression and the suppression mechanism (2008)
  • Author(s): Hori M, Suzuki K, Udono MU, Yamauchi M,Mine M, Watanabe M, Kondo S, Hozumi Y
  • Journal Title: Arch Dermatol Res Nov 14
• [Journal Article] p53 status-dependent sensitization of humantumour cells to hyperthermia by plant flavonol (2008)
  • Author(s): Hamamoto T, Suzuki K, Yamauchi M,Kodama S, Sasaki H, Watanabe M
  • Journal Title: Int J Hyperthermia 24 Pages: 415-425
• [Journal Article] Growth of persistent foci of DNA damage checkpoint factors is essential for amplification of G1 checkpoint signaling (2008)
  • Author(s): Yamauchi M, Oka Y, Yamamoto M, Niimura K, Uchida M, Kodama S, Watanabe M, Sekine I, Yamashita S, Suzuki K
  • Journal Title: DNA Repair(Amst) 7 Pages: 405-417
• [Journal Article] Different involvement of radical species in irradiated and bystander cells (2008)
  • Author(s): Harada T, Kashino G, Suzuki K, Matsuda N, Kodama S, Watanabe M
  • Journal Title: Int J Radiat Biol 84 Pages: 809-814
• [Journal Article] Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2 (2008)
  • Author(s): Takada S, Inoue E, Tano K, Yoshii H, Abe T, Yoshimura A, Akita M, Tada S, Watanabe M, Seki M, Enomoto T
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 233-238
• [Journal Article] Alteration of p53-binding protein 1 expression during skin carcinogenesis : association with genomic instaibility (2008)
  • Author(s): Naruke Y, Nakashima M, Suzuki K, Matsuu-Matsuyama M, Shichijo K, Kondo H, Sekine I
  • Journal Title: Cancer Sci 99(5) Pages: 946-951
• [Journal Article] Foci formation of p53-binding protein 1 in thyroid tumors:activation of genomic instaibility duringthyroid carcinogenesis (2008)
  • Author(s): Nakashima M, Suzuki K, Meirmanov S, Naruke Y, Matsuu-Matsuyama M, Shichijo K, Saenko V, Kondo H, Hayashi T, Ito M,Yamashita S, Sekine I
  • Journal Title: Int J Cancer 122(5) Pages: 1082-1088
• [Presentation] Mitchondria and cell transformation, In an International Symposim on "The participation of the energy metabolic system in radiation carcinogenesis process" (2008)
  • Author(s): Yoshi H, Watanabe M
  • Organizer: The 51th Annual Meeting of Japanese Radiation Research Society
  • Place of Presentation: Kokura(Invited)
  • Year and Date: 20081119-21
• [Presentation] Mutagenic slow releasing long-lived radicals are produced from dysfunctional mitochondria (2008)
  • Author(s): Kumagai J, Miura K, Kashino, Watanabe M
  • Organizer: In an International Symposim on "The participation of the energy metabolic systemin radiation carcinogenesis process",The 51thAnnual Meeting of Japanese RadiationResearch Society
  • Place of Presentation: (Invited)
  • Year and Date: 20081119-21
• [Presentation] The mainroute of radiation-induced carcinogenesis isthe same as that of natural carcinogenesis (2008)
  • Author(s): Watanabe M, Yoshii H, Watanabe K
  • Organizer: The 54th Annual Meeting of the Radiation Research Society
  • Place of Presentation: Boston, USA(Invited)
  • Year and Date: 20080921-24
• [Presentation] Target of radiation carcinogenesis is protein (2008)
  • Author(s): Watanabe M
  • Organizer: The First InternationalSymposium on the Establishment of a NewDiscipline" Medical Care for Hibakusha"
  • Place of Presentation: Nagasaki(Invited)
  • Year and Date: 20080131-0201
• [Presentation] Is there a non-targeted route in radiation carcinogenesis? Is There a Non-targeted Route in Radiation Carcinogenesis Process? -Candidate Playing an Important Role (2008)
  • Author(s): Watanabe M
  • Organizer: In an International Symposium of Kyoto University RRI
  • Place of Presentation: Kumatori, Japan(Invited)
  • Year and Date: 2008-12-18
• [Presentation] How to set Ikaros up as the villain in radiation lymphoma-genesis (2008)
  • Author(s): Simada Y
  • Organizer: In an International Symposium of Kyoto University RRI
  • Place of Presentation: Kumatori, Japan(Invited)
  • Year and Date: 2008-12-18
• [Presentation] Amplification of intranuclear DNA damaging signal reduces genome reorganization involved in radiation-induced carcinogenesis (2008)
  • Author(s): Suzuki K
  • Organizer: in an International Symposium of Kyoto University RRI
  • Place of Presentation: Kumatori, Japan(Invited)
  • Year and Date: 2008-12-18
• [Presentation] A Role of Chromosomal Instability in Carcinogenesis and Cellular Senescence (2008)
  • Author(s): Kodama S
  • Organizer: in an International Symposium of Kyoto University RRI
  • Place of Presentation: Kumatori, Japan(Invited)
  • Year and Date: 2008-12-18
• [Presentation] Main route of radiation-carcinogenesis is DNA damage- independentpathway. (2007)
  • Author(s): Watanabe M, Yoshii H, Watanabe K, Suzuki K, Kodama S, Kumagai J
  • Organizer: 13th International Congress of Radiation Research
  • Place of Presentation: San Francisco(Invited)
  • Year and Date: 20070708-12
• [Presentation] Plenary Lecture I, The mainroute of radiation carcinogenesis-The firsttarget of radiation-induced carcinogenesis isnot DNA (2007)
  • Author(s): Watanabe M
  • Organizer: International Symposium of Korea University Brain Korea 21 Program for Biomedical Sciences
  • Place of Presentation: Seoul(Invited)
  • Year and Date: 2007-01-23
• [Book] 突然変異は放射線発がんの主因ではない、モデルが拓く放射線防護研究の新たな展開-第一回放射線防護研究センターシンポジウム(根井充編)(64-70) (2007)
  • Author(s): 渡辺正己
  • Total Pages: 64-70
  • Publisher: 放射線医学総合研究所
• [Book] 放射線発がんの主たる標的はDNAではない可能性が高い(25(5)) (2007)
  • Author(s): 渡辺正己
  • Total Pages: 176-181
  • Publisher: ESI-NEWS
• [Remarks]
  • URL: http://www.rri.kyoto-u.ac.jp/rb-rri/