Cell transformation route and the developmental mechanics which assumed chromosomal aneuploidy an origin

• Project/Area Number: 21310036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Masami 京都大学, 原子炉実験所, 教授 (20111768)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2009: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
• Keywords: 染色体異数化 / 中心体 / 細胞がん化 / ミトコンドリア機能 / 自然発がん / メロテリック結合 / 長寿命ラジカル / 微小核細胞融合法 / 擬二極分裂 / 染色体取り残し / 放射線発がん / 三倍体 / 四倍体 / 遺伝子発現

Research Abstract

It has been believed that the first target of radiation carcinogenesis is DNA. However, this is not proved for radiation carcinogenesis yet. We discovered that frequency of aneuploid cell was closely related to that of radiation-induced cell transformation, but gene mutation was not. Aneuploidy was seen in high frequency in early process of cell transformation. These results strongly suggest that a main target of carcinogenesis by low dose radiation is not DNA, but is centrosome, which are the proteins to constitute chromosomal homeostasis maintenance mechanism.

Research Products

• [Journal Article] 放射線発がんの主経路は染色体異数化を起源とする (2012)
  • Author(s): 渡邉正己
  • Journal Title: 保健物理 Volume: (印刷中)
  • NAID: 10030494860
  • Peer Reviewed
• [Journal Article] 放射線誘導長寿命ラジカルがDNA損傷を起源としない発がん経路の引き金 (2012)
  • Author(s): 渡邉正己、菓子野元郎、熊谷純
  • Journal Title: 日本化学会学会誌 Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Micronuclei formation induced by X-irradiation does not always result from DNA double-strand breaks (2012)
  • Author(s): Okada T, Kashino G, Nishiura H, TanoK, Watanabe M.
  • Journal Title: J Radiat Res(Tokyo) Volume: 53(1) Pages: 93-100
  • Peer Reviewed
• [Journal Article] The bystander effect is a novel mechanism of UVA-induced melanogenesis (2012)
  • Author(s): Nishiura H, Kumagai J, Kashino G, Okada T, Tano K, Watanabe M
  • Journal Title: Photochemistry and Photobiology Volume: 88(2) Pages: 389-397
  • Peer Reviewed
• [Journal Article] Micronuclei formation induced by X-irradiation does not always result from DNA double-strand breaks (2012)
  • Author(s): Okada T, Kashino G, Nishiura H, Tano K, Watanabe M
  • Journal Title: J Radiat Res (Tokyo) Volume: 53(1) Pages: 93-100
  • Peer Reviewed
• [Journal Article] 放射線生体影響を科学的に評価することが放射線防護の基盤-LNT仮説を見直す必要がある (2011)
  • Author(s): 渡邉正己
  • Journal Title: 特集保健物理からか対する放射線生物研究 Volume: 29(1) Pages: 1-4
• [Journal Article] Epigenetic gene silencing is a novel mechanism involved in delayed manifestation of radiationinducedgenomic instability in mammalian cells (2011)
  • Author(s): Suzuki K, Yamaji H, Kobashigawa S, Kawauchi R, Shima K, Kodama S, Watanabe M
  • Journal Title: Radiat Res Volume: 175(4) Pages: 416-423
  • Peer Reviewed
• [Journal Article] UV B-irradiation enhances the racemization and isomerizationof aspartyl residues and production of N(.)-carboxymethyl lysine(CML) in keratin of skin (2011)
  • Author(s): Mori Y, Aki K, Kuge K, Tajima S, Yamanaka N, Kaji Y, Yamamoto N, Nagai R, Yoshii H, Fujii N, Watanabe M, Kinouchi T, Fujii N.
  • Journal Title: J Chromatogr B Volume: 879(29) Pages: 3303-3309
  • Peer Reviewed
• [Journal Article] Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes (2011)
  • Author(s): Nawata H, Kashino G, Tano K, Daino K, Shimada Y, Kugoh H, Oshimura M, Watanabe M.
  • Journal Title: Pros ONE Volume: 6(9)
  • Peer Reviewed
• [Journal Article] Usefulness of hexamethylene tetramineas an adjuvant to radiation andcisplatin in the treatment of solidtumorsits independency of p53 status (2011)
  • Author(s): Masunaga S, Tano K, Nakamura J, Watanabe M, Kashino G, Takahashi A, Tanaka H, Suzuki M, Ohnishi K, Kinashi Y, Liu Y, Ohnishi T, Ono K
  • Journal Title: J Radiat Res(Tokyo) Volume: 51(1) Pages: 27-35
  • Peer Reviewed
• [Journal Article] Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes (2011)
  • Author(s): Nawata H, Kashino G, Tano K, Daino K, Shimada Y, Kugoh H, Oshimura M, Watanabe M
  • Journal Title: Pros ONE Volume: 6(9)
  • Peer Reviewed
• [Journal Article] Epigenetic Gene Silencing is a Novel Mechanism Involved in Delayed Manifestation of Radiation-Induced Genomic Instability in Mammalian Cells (2011)
  • Author(s): Suzuki K, Yamaji H, KObashigawa S, Kawauchi R, Shima K, Kodama S, Watanabe M
  • Journal Title: Radiat Res Volume: 175 Pages: 416-423
  • Peer Reviewed
• [Journal Article] An alternative mechanism for radioprotection by dim ethyl sulfoxide ; possible facilitation of DNA doublestrandbreak repair (2010)
  • Author(s): Kashino G, Liu Y, Suzuki M, MasunagaS, Kinashi Y, Ono K, Tano K, WatanabeM
  • Journal Title: J Radiat Res(Tokyo) Volume: 51(6) Pages: 733-470
  • Peer Reviewed
• [Journal Article] Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation (2010)
  • Author(s): Suzuki K, Kodama S, Watanabe M
  • Journal Title: Mutat Res Volume: 683(1-2) Pages: 29-34
  • NAID: 120006983691
  • Peer Reviewed
• [Journal Article] SOD1 Is essential for the viability ofDT40 cells and nuclear SOD1 Functions as a guardian of genomic DNA (2010)
  • Author(s): Inoue E, Tano K, Yoshii H, Nakamura J, Tada S, Watanabe M, Seki M, EnomotoT
  • Journal Title: JNucleic Acids Volume: 5 Pages: 795946-795946
  • Peer Reviewed
• [Journal Article] FEN1functions in long patch base excision repair under conditions of oxidative stress in vertebrate cells (2010)
  • Author(s): Asagoshi K, Tano K, Chastain PD 2nd, Adachi N, Sonoda E, Kikuchi K, Koyama H, Nagata K, Kaufman DG, Takeda S, Wilson SH, Watanabe M, Swenberg JA, Nakamura J
  • Journal Title: Mol Cancer Res Volume: 8(2) Pages: 204-215
  • Peer Reviewed
• [Journal Article] DNA polymerases nuand theta are required for efficient immunoglobulin V gene diversification in chicken (2010)
  • Author(s): Kohzaki M, Nishihara K, Hirota K, Sonoda E, Yoshimura M, Ekino S, Butler JE, Watanabe M, HalazonetisTD, Takeda S
  • Journal Title: J Cell Biol Volume: 189(7) Pages: 1117-1127
  • Peer Reviewed
• [Journal Article] Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine in the treatment of solid tumors : compared with its effect combined with tirapazamine (2010)
  • Author(s): Masunaga SI, Tano K, Nakamura J, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Ono K
  • Journal Title: Exp Ther Med Volume: 1 Pages: 169-174
  • Peer Reviewed
• [Journal Article] SOD1 Is essential for the viability ofDT40 cells and nuclear SOD1 functions as a guardian of genomic DNA (2010)
  • Author(s): Asagoshi K, Tano K, Chastain PD 2nd, Adachi N, Sonoda E, Kikuchi K, Inoue E, Tano K, Yoshii H, Nakamura J, Tada S, Watanabe M, Seki M, Enomoto T
  • Journal Title: JNucleic Acids Volume: 5 Pages: 795946-795946
  • Peer Reviewed
• [Journal Article] SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA (2010)
  • Author(s): Inoue E, Tano K, Yoshii H, Nakamura J, Tada S, Watanabe M, Seki M, Enomoto T
  • Journal Title: J Nucleic Acids (On Line Journal) Volume: 2010
  • Peer Reviewed
• [Journal Article] An alternative mechanism for radioprotection by dimethyl sulfoxide ; possible facilitation of DNA double-strand break repair. (2010)
  • Author(s): Kashino G, Liu Y, Suzuki M, Masunaga S, Kinashi Y, Ono K, Watanabe M
  • Journal Title: J Radiat Res Volume: 51 Pages: 733-740
  • NAID: 10026964239
  • Peer Reviewed
• [Journal Article] Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylatedliposomal doxorubicin in vivo, referring to the effect on quiescent cells (2009)
  • Author(s): Masunaga S, Kono K, Nakamura J, Tano K, Yoshida H, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Liu Y, Ono K
  • Journal Title: Oncol Rep Volume: 21(5) Pages: 1307-1312
  • Peer Reviewed
• [Journal Article] Evaluation of the potential of hexamethylenetetramine, compared withtirapazamine, as a combined agent with gamma-irradiation and cisplatin treatment in vivo (2009)
  • Author(s): Masunaga S, Tano K, Watanabe M, Kashino G, Suzuki M, Kinashi Y, OnoK
  • Journal Title: Br J Radiol Volume: 82(977) Pages: 392-400
  • Peer Reviewed
• [Journal Article] Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing anhTERT gene (2009)
  • Author(s): Ariyoshi K, Suzuki K, Goto M, Oshimura M, Ishizaki K, Watanabe M, Kodama S
  • Journal Title: J Radiat Res(Tokyo) Volume: 50(3) Pages: 253-259
  • Peer Reviewed
• [Journal Article] Induction of DNA double-strand breaks and cellular migration through bystander effects in cells irradiated with the slit-type micro planar 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, LiuYong, Masunaga S, Watanabe M, Ono K
  • Journal Title: Intern JRadiat Oncol Biol Phys Volume: 74(1) Pages: 229-236
  • Peer Reviewed
• [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 Volume: 171(12) Pages: 198-203
  • Peer Reviewed
• [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 Radiat Res(Tokyo) Volume: 50(2) Pages: 127-137
  • NAID: 10025911412
  • Peer Reviewed
• [Journal Article] Phosphorylated H2AXfoci 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) Volume: 50(2) Pages: 151-160
  • NAID: 10025911507
  • Peer Reviewed
• [Journal Article] Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over thePARP-1-proficient cells exposed to MMS (2009)
  • Author(s): Pachkowski BF, Tano K, Afonin V, Elder RH, Takeda S, Watanabe M, Swenberg JA, Nakamura J
  • Journal Title: Mutat Res Volume: 671(1-2) Pages: 93-99
  • Peer Reviewed
• [Journal Article] Long-term persistence ofX-ray-induced genomic instability in quiescent normal human diploid cells (2009)
  • Author(s): Suzuki K, Kashino G, Kodama S, Watanabe M
  • Journal Title: Mutat Res Volume: 671(1-2) Pages: 33-39
  • Peer Reviewed
• [Journal Article] Establishment of ponasterone A-inducible the wild-typep53 protein-expressing clones fromHSC-1 cells, cell growth suppression byp53 expression and the suppression mechanism (2009)
  • Author(s): Hori M, Suzuki K, Udono MU, Yamauchi M, Mine M, Watanabe M, Kondo S, Hozumi Y
  • Journal Title: Arch Dermatol Res Volume: 301(9) Pages: 631-646
  • Peer Reviewed
• [Journal Article] Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2 (2009)
  • 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(2) Pages: 233-238
  • Peer Reviewed
• [Journal Article] Long-term persistence of X-ray-induced genomic instability in quiescent normal human diploid cells (2009)
  • Author(s): Suzuki K, Kashino G, Kodama S, Watanabe M
  • Journal Title: Mutation Res 671(1-2) Pages: 33-39
  • NAID: 120006983991
  • Peer Reviewed
• [Journal Article] Introduction of a normal human chromosome 8 corrects abnormal phenotype of Werner syndrome cells immortalized by expressing an hTERT gene (2009)
  • Author(s): Ariyoshi K, Suzuki K, Goto M, Oshimura, Ishizaki K, Watanabe M, Kodama S
  • Journal Title: J Radiat Res 50(3) Pages: 93-99
  • NAID: 10025911840
  • Peer Reviewed
• [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 17182 Pages: 198-203
  • Peer Reviewed
• [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 Radiat Res 50(2) Pages: 127-137
  • NAID: 10025911412
  • Peer Reviewed
• [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 50(2) Pages: 151-160
  • NAID: 10025911507
  • Peer Reviewed
• [Journal Article] Target of radiation carcinogenesis is protein : Becoming triploid is proximate cause of cell transformation (2009)
  • Author(s): Watanabe M, Yoshii H
  • Journal Title: Radiation Health Risk Sciences(eds by Nakashima M, et al.) Springer Pages: 212-215
• [Presentation] 放射線発がんにおけるミトコンドリア機能撹乱の関与 (2011)
  • Author(s): 渡邉正己、田野恵三、渡邉喜美子、菓子野元郎、熊谷純
  • Organizer: 日本放射線影響学会
  • Place of Presentation: 神戸商工会議所会館(兵庫)
  • Year and Date: 2011-11-17
• [Presentation] The origin of radiation carcinogenesis is not DNA damage (2011)
  • Author(s): Hasami Watanabe, Kimiko Watanabe, Genro Kashino, Jun Kumagai, Keizo Tano
  • Organizer: International Congress of Radiation Reearch
  • Place of Presentation: Warszawa, Poland
  • Year and Date: 2011-08-30
• [Presentation] 放射線発がんへのミトコンドリアの関与、ワークショップ『放射線生物学と活性酸素(酸化ストレス)-ミトコンドリアの役割-』 (2011)
  • Author(s): 渡邉正己、菓子野元郎、熊谷純、渡邉喜美子、田野恵三
  • Organizer: 第54回日本放射線影響学会学術大会
  • Place of Presentation: 神戸
• [Presentation] Biological effects of low dose radiation, A Symposium on"UrgentSymposium for The accidents in Fukushima Daiichi nuclear power plant" (2011)
  • Author(s): Watanabe M
  • Organizer: IUPAC International Congress of Analytical Sciences 2011
  • Place of Presentation: Kyoto, Japan.(Invited)
• [Presentation] Non-targeted effects-its mechanism and significance (2011)
  • Author(s): Watanabe M, Watanabe K, Kashino G, Kumagai J, Tano K. Symposium on
  • Organizer: 14th International Congress of Radiation Research 2011
  • Place of Presentation: Warszawa, Poland.(Invited)
• [Presentation] The origin of radiation carcinogenesis is chromosomal aneuploid (2010)
  • Author(s): Watanabe M, Watanabe K, Kashino G, Nawata H, Tano K, Kumagai J, Watanabe M, Watanabe K, Kashino G, Nawata H, Tano K, Kumagai J
  • Organizer: In a Symposium of European Radiation Reseach Society 2010
  • Place of Presentation: Stockholm, Sweden.(Invited)
• [Presentation] The origin of radiation carcinogenesis is chromosomal aneuploid (2010)
  • Author(s): Watanabe M, Watanabe K, Kashino G, Nwawata T, Tano K, Kumagai J
  • Organizer: European Radiation Research
  • Place of Presentation: Stockholm
• [Presentation] Carcinogenesis by low dose radiation passes through the same route as natural carcinogenesis (2009)
  • Author(s): Watanabe M, Watanabe K, Yoshii H, Nawata H, Tano K
  • Organizer: 37th Annual Meeting of the European Radiation Research Society
  • Place of Presentation: Prague
• [Presentation] Aneuploidy cause cell transformation (2009)
  • Author(s): Nawata H, Yoshii H, Watanabe M
  • Organizer: 55th Annual Meeting of Radiation Research Society
  • Place of Presentation: Savannah, GA
• [Presentation] The role of radicals in bystander effect through the secreted factors from irradiated cells (2009)
  • Author(s): Kashino G, Kumagai J, Ono K, Watanabe M
  • Organizer: 55th Annual Meeting of Radiation Research Society
  • Place of Presentation: Savannah, GA
• [Remarks]
  • URL: http://www.rri.kyoto-u.ac.jp/rb-rri/