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RADIATION-INDUCED LONG LIVED RADICALS CAUSING MUTATION AND TRANSFORMATION

Research Project

Project/Area Number 13480171
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionNagasaki University

Principal Investigator

WATANABE Masami  Nagasaki University, Graduate Stool of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20111768)

Co-Investigator(Kenkyū-buntansha) KODAMA Seiji  Nagasaki University, Graduate Stool of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (00195744)
鈴木 啓司  長崎大学, 大学院・医歯薬学総合研究科, 助手 (00196809)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsLong-lived radicals / Vitamin C / Mutation / Transformation / Chromosome aberration Cell Death / 細胞死 / スルフィニル基 / 細胞癌化
Research Abstract

Many researches studying in area of radiation biology have been believed that active short life-time radicals such as OH and H radicals, play an important role to express genoto do effects of radiation h cells, such as mutation and cancer induction. However, we found a new type of radicals with long life-time (T_<1/2>20hr) in gamma ray hmdiated golden hamster embryo (GHE) cells at room temperature by using ESR spectroscopy. It may be more important in mutation induction than the active short live radials. When Vitamin C (MA) is added to the gamma-or X-irradiated cells at 20 min or 6 hr after the irradiation, respectively, LLR are scavenged by them simuhaneousty with the drastic suppression of genotoxicity such as mutation and transformation. Since reactive oxygen species (ROS) disappear within microsecond after the irradiation, AsA do not scavenge the ROS but LLR. Therefore, we have proposed that LLR must be responsible radicals for inducing mutation, and probably important for the genotoxicity in the irradiated mammalian cells. Addition of AsA to the cells before or after irradiation does not have any effects on reducing cell death and chromosomal aberration. By the studies using ESEEM spectroscopy, we found that LLR probably locate in interior of biopolymers where few water molecules exist. By further analysis of the ESR spectra of LLR and comparison of the yields of radicals in proteins and DNA, we reached to the conclusion that LLR are produced in protein and assigned as sulfinyl radicals as oxidized cysteine groups. LLR are not produced in DNA or in lipids. Our result show that the LLR produced in protein is responsible for the gene mutation in irradiated cells. Although this contradicts now common view in the radiation biology, many unresolved phenomena in the radiation biology can be explained well.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Tominaga, H., Kodama S, Matsuda, N., Suzuki, K., Watanabe, M: "Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation"J.Radiat.Res.. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Urushibara A, Kodama S, Suzuki K, Desa M.B., Suzuki F, Tsutsui T, Watanabe M.: "Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells"Biochem Biophys Res Commun.. 313・4. 1037-1043 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Undarmaa, B., Kodama, S., Suzuki, K., Niwa, O., Watanabe, M.: "X-ray-induced telomeric instability in Atm-deficient mouse cells"Biochem Biophys Res Commun.. 315. 51-58 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hamada, N., Kodama, S., Suzuki, K., Watanabe, M.: "Gap junctional intercellular communication and cellular response to heat stress"Carcinogenesis. 24・11. 1723-1728 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagai, J., Masui, K., Itagaki, Y., Shiotani., Kodama, S., Watanabe, M., Miyazaki, T.: "Long-loved mutagenic radicals induced in mammalian cells by ionaizing radiation are mainly localized to proteins"Radiat.Res.. 160・1. 95-102 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashino, G., Kodama, S., Nakayama, Y., Suzuki, K., Fukase, K., Goto, M, Watanabe, M.: "Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrime fibroblast cells."Free Radical Biology and Medicine. 35・4. 438-443 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ghosh, J.D., Izumida, Y., Suzuki, K., Kodama, S., Watanabe, M.: "Dose-dependent biphasic accumulation of p53 protein in normal human embryo cells following X-irradiation."Radiat.Res.. 53. 305-311 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki, M., Nakano, K., Suzuki, K., Watanabe.M.: "Influence of the sampling time on chromosomal aberrations at G2 phase h Syrian hamster embryonic cells irradiated with different types of radiation."Int.J.Radiat.Biol.. 76(6). 8154-8821 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Roy, K., Kodama, S., Suzuki, K., Fukase, F., Watanabe.M.: "Hypoxi relieves X-ray-induced delayed effect in normal human embryo cells."Radiat.Res.. 154. 659-666 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagai, J., Kumada, T., Watanabe.M., Miyazaki, T.: "Electron spin echo study of long-lived radicals which cause mutation in gamma-ray irradiated mammalian cells."Spectrochimica Acta Part A : Mol. & BiomolSpectrvscopy. 56. 2509-2516 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuda, N., Horikawa, M., Wang, L.-H., Yoshida, M., Okaichi, K., Okumura, Y., Watanabe, M.: "Differential activation of ERK 1/2 and JNK in normal human fibroblast-like cells in response to UVC radiation under different oxygen tensions."Photo chem. Photobiol. 72. 334-339 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki, K., Kodama, S., Watanabe, M.: "Extremely low-dose ionizing radiation causes activation of MAP kinase pathway and enhances proliferation of normal human diploid cells."Cancer Res.. 61(14). 5396-5401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yanase, H., Ando, H., Horikawa, M., Watanabe.M., Mori, T., Matsuda, N.: "Possible involvement of ERK 112 in UVA-induced melanogenesis in cultured normal human epidermal melanocyles."Pigment Cell Res.. 14(2). 103-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kodama, S., Suzuki, K., Watanabe.M.: "Culure condition dependent senescence like growth arrest and immortalization in rodent embryo cells."Radiat.Res.. 155(1 Pt2). 254-262 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki, K., Mori, I., Nakayama, Y., Miyakoda, M., Kodama, S., Watanabe.M.: "Radiation-induced senescence-like growth arrest requires p53 function, but not telomere shortening."Radiat.Res.. 155(1 Pt2). 248-253 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashino, G., Kodama, S., Suzuki, K., Oshimura, M., Watanabe, M: "Preferential expression of an intact WRN gene in Wemer Syndrome cell lines in which a normal chromosome 8 has been introduced"Biochem.Biophys.ResCommun.. 289(1). 111-115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyakoda, M., Suzuki, K., Kodama, S., Watanabe, M.: "Activation of ATM by heat shock and phosphorylation of p53."Oncogene. 21(7). 1090-1096 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakahata, K., Miyakoda, M., Suzuki, K., Kodama, S., Watanabe, M.: "Heat shock induces centrosomal dysfunction, and causes non-apoptotic catastrophe in human tumor cells."Intern.J Hyper. (Japanese). 18(4). 332-343 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagai, J., Nakama, M., Miyazaki, T., Ise, T., Kodama, S., Watanabe, M.: "Scavenging of long-lived radicals by (-)-epigalloctechin-3-O-gallate and simultaneous suppression of mutation in irradiated mammalian cells."Radiat.Phys.Chem.. 64. 293-297 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki, K., Yokoyama, S., Waseda, S., Kodama, S., Watanabe, M.: "Delayed reactivation of p53 in the progeny of cells surviving ionizing radiation."Cancer Res.. 63(Mar.1). 936-941 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagai, J., Maui, K., Itagaki, J., Shiotani, M., Kodama, S., Watanabe, M., Miyazaki, T.: "Long-lived, mutagenic radicals induced in mammalian cells by ionizing radiation are mainly localized to proteins."Radiat Res.. 160(1). 95-102 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hamada, N., Kodama, S., Suzuki, K., Watanabe, M.: "Gap junctional intercellular communication and cellular response toheat stress."Caminogenesis. 24(11). 1723-1728 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashino, G., Kodama, S., Nakayama, Y., Suzuki, K., Fukase, K., Goto, M., Watanabe, M.: "Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Wemer syndrome fibroblast cells."Free Radical Biology and Medicine. 35(4). 438-443 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuda, N., Horikawa, M., Yoshida, M., Watanabe.M, Nagahata, M., Teramoto, A., Abe, K: "Enhanced DNA synthesis accompanied by constitutive phaophorylation of the ERK pathway in human fibroblasts cultured on a polyeectrolyte complex."Biomaterials. 24. 4771-4776 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki, K, Ojima, K, Kodama, S., Watanabe, M.: "Radiation-induced DNA damage and delayed induced genomic instability."Oncogene. 22. 6988-6993 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki M., Tsuruoka, C., Kanai, T., Kato, T., Yatagai, F., Watanabe.M: "Qualitative and quantitative difference in mutation induction between carbon-and neon-ion beams in normal cells."Biol Sci.Sapce. 17(4). 302-305 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagai, J, Kawaura, T., M yazaki, T., Prosy, M, Prost, E, Watanabe, M., Quetin-Leclercq, J.: "Test for antioxidant ability by scavenging long-lived mutagenic radicals in mammalian cells and by blood test with intentional radicals : An application of gallic acid. Radiat."Radiat.Phys.Chem.. 66. 17-25 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Urushibara, A, Kodama, S, Suzuki, K, Desa MB., Suzuki, F., Tsutsui, T., Watanabe, M.: "Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells."Biochem.Biophys Res.Commun. 313(4). 1037-1043 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Undarmaa, B, Kodama, S, Suzuki, K, Niwa, O., Watanabe, M.: "X-ray-induced telomeric instability in Aim-deficient mouse cells."Biochem.Biophys Res.Commun. 315(1). 51-58 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ojima, M, Hamano, H, Suzuki, M, Suzuki, K, Kodama, S., Watanabe, M.: "Delayed induction of telomere instability in normal human fibroblast cells by ionizing radiation."J.Radiat Res.. 45(1). 1-13 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tominaga, H, Kodama S, Matsuda, N., Suzuki, K, Watanabe, M.: "Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation."J.Radiat Res.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tominaga, H., Kodama S, Matsuda, N., Suzuki, K., Watanabe, M: "Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation"J.Radiat.Res.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Urushibara A, Koddama S, Suzuki K, Desa M.B., Suzuki F, Tsutsui T, Watanabe M.: "Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells"Biochem Biophys Res Commun.. 313・4. 1037-1043 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Undarmaa, B., Kodama, S., Suzuki, K., Niwa, O., Watanabe, M.: "X-ray-induced telomeric instability in Atm-deficient mouse cells"Biochem Biophys Res Commun.. 315. 51-58 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamada, N., Kodama, S., Suzuki, K., Watanabe, M.: "Gap junctional intercellular communication and cellular response to heat stress"Carcinogenesis. 24・11. 1723-1728 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kumagai, J., Masui, K., Itagaki, Y., Shiotani, M., Kodama, S., Watanabe, M., Miyazaki, T.: "Long-loved mutagenic radicals induced in mammalian cells by ionaizing radiation are mainly localized to proteins"Radiat.Res.. 160・1. 95-102 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kashino, G., Kodama, S., Nakayama, Y., Suzuki, K., Fukase, K., Goto, M., Watanabe, M.: "Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrime fibroblast cells"Free Radical Biology and Medicine. 35・4. 438-443 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] G.Kashini, S.Kodama, K.Suzuki, M.Oshimura, M.Watanabe: "Preferential expression of an intact WRN gene in Werner Syndrome cell lines in which a normal chromosome 8 has been introduced"Biophys. Biochem. Res. Commun.. 289・1. 111-115 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Miyakoda, K.Suzuki, S.Kodama, M.Watanabe: "Activation of ATM by heat shock and phosphorylation of p53"Oncogene. 21・7. 1090-1096 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Nakahata, M.Miyakoda, K.Suzuk i, S.Kodama, M.Watanabe: "Heat shock induces centrosomal dysfunction, and causes non-apoptotic catastrophe in human tumor cells"Intern. J. Hyper.. 18・4. 332-343 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Goto, M.Watanabe, F.Yatagai: "Delayed cell cycle progression in human lymphoblastoid cells radiation correlates with the extremely localized DNA damage"Radiat. Res.. 158. 678-686 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] J.Kumagai, M.Nakama, T.Ise, S.Kodama, M.Watanabe, T.Miyazaki: "Scavenging of long-lived radicals by (-)-epigallocatechin-3-O-gallate and simultaneous suppression of mutation in irradiated mammalian cells"Radiat. Phys. Chem.. 64. 293-297 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, S.Yokoyama, S.Waseda, S.Kodama, M.Watanabe: "Delayed reactivation of p53 in the progeny of cells surviving ionaizing"Cancer Res.. 63(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] G.Kashino, S.Kodama, K.Suzuki, M.Oshimura, M.Watanabe: "Preferential expression of an intact WRN gene in Werner Syndrome cell lines in which a normal chromosome 8 has been introduced"Biophys.Biochem.Res.Commun. 289・1. 111-115 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Miyakoda, K.Suzuki, S.Kodama, M.Watanabe: "Activation of ATM by heat shock and phosphorylation of p53"Oncogene. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Nakahata, M.Miyakoda, K.Suzuki, S.Kodama, M.Watanabe: "Heat shock induces centrosomal dysfunction, and causes non-apoptotic catastrophe in human tumor cells"Intern.J.Hyper.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] J.Kumagai, T.Kawaura, T.Miyazaki, M.Prost, E.Prost, M.Watanabe, J.Quetin-Leclercq: "Analysis of the Protective Effects of Gallic Acid Against Long-Lived Radicals Produced in g-ray Irradiated Cells and against Hemolysis Produced by Chemical Radicals in Blood Cells. Comparison of Both Methods"Free Radical Res.. (in Press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] J.Kumagai, M.Nakama, T.Ise, S.Kodama, M.Watanabe, T.Miyazaki: "Scavenging of long-lived radicals by (-)-epigallocatechin-3-0-gallate and simultaneous suppression of mutation in irradiated mammalian cells"Radiat.Phys.Chem.. (in Press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Suzuki, S.Kodama, M.Watanabe: "Extremely low-dose ionizing radiation causes activation of MAP kinase pathway and enhances proliferation of normal human diploid cells"Cancer Res.. 61・14. 5396-5401 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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