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Studies on characteristics and mechanism of radiation carcinogenesis in radiosensitive strains of mice

Research Project

Project/Area Number 11670233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

OGIU Toshiaki  National Institute of Radiological Sciences, Low Does Radiation Effects Research Project, Project Leader, 放射線安全研究センター・低線量生体影響プロジェクト, プロジェクトリーダー (40106183)

Co-Investigator(Kenkyū-buntansha) TSUJI Hideo  National Institute of Radiological Sciences, Ditto, Team Leader, 放射線安全研究センター・低線量生体影響プロジェクト, チームリーダー (40163795)
ISHII Hiroko (OHBA Hiroko)  National Institute of Radiological Sciences, Ditto, Senior Researcher, 放射線安全研究センター・低線量生体影響プロジェクト, 主任研究員 (70159672)
SHIMADA Yoshiya  National Institute of Radiological Sciences, Ditto, Sub-Project Leader, 放射線安全研究センター・低線量生体影響プロジェクト, サブプロジェクトリーダー (10201550)
NISHIMURA Mayumi  National Institute of Radiological Sciences, Ditto, Senior Researcher, 放射線安全研究センター・低線量生体影響プロジェクト, 主任研究員 (70218204)
UKAI Hideki  National Institute of Radiological Sciences, Ditto, National Institute Post Doctoral Fellow, 放射線安全研究センター・低線量生体影響プロジェクト, (研究協力者)科学技術特別研究員
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsRadiation carcinogenesis / C.B-17 Scid mice / DNA repair / DNA-PKcs / C.B-17 mice / Thymic lymphoma / Nochi1 / Mutation / 放射線発ガン / Notch1 / 遺伝子欠失 / 骨髄移植 / Y染色体
Research Abstract

The C.B-17 Scid mouse demonstrates immunodeficiency and also radio sensitivity similar to human ataxia-telangiectasia because of mutation in the DNA-PKcs gene. This strain of mice was also susceptible to radiation induction of thymic lymphomas. Therefore, characteristics of radiation carcinogenesis and molecular mechanisms were examined in this study. Scid, C.B-17 and their hybrid F1 mice were irradiated with gamma-rays and spectrum of carcinogenesis was first examined. Scid mice were extremely susceptible to the induction of thymic lymphomas by ionizing radiation, but not C.B-17 and F1 mice. Then irradiated Scid mice were transplanted with normal bone marrow cells of C.B-17 mice just after gamma-ray-irradiation to suppress induction of thymic lymphomas and thereby to examine carcinogenesis in various organs other than the thymus. This treatment completely reduced development of thymic lymphomas, but no excess of other tumors was demonstrated comparing with that in C.B-17 and F1 mice. Next, Scid mice with C3H background (C3H Scid mice) were used to examine effects of genetic background on radiosensitivity and radiation carcinogenesis. C3H Scid were demonstrated to be more radiosensitive and more susceptible to radiation induction of thymic lymphomas compared with C.B-17 Scid mice. Furthermore, presence of modifier gene was suspected Mutations of various cancer-related genes were examined with thymic lymphomas, and mutation of the Notch1 gene encoding cell surface receptor was frequently observed. Length of this gene is 45.6 kb with 34 exons. Although Genomic rearrangement was observed in about 20% of thymic lymphomas of STS and C.B-17 mice, that was more frequent in C.B-17 Scid mice. Detected rearrangements are deletion, IAP insertion and inversion. Furthermore, abnormal mRNA and protein were demonstrated in the tumors. Then, it is suggested that Notch1 gene is an oncogene, which is continuously active and may have a important role in thymic lymphomagenesis.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (38 results)

All 2002 2001 2000 1999 1997 Other

All Journal Article (14 results) Book (1 results) Publications (23 results)

  • [Journal Article] Spectrum of Znfn1a1 (Ikaros) inactivation and its association with loss of heterozygosity in radiogenic T-cell lymphomas in susceptible B6C3F1 mice.2002

    • Author(s)
      Kakinuma, S., Nishimura, M., Sasanuma, S., Mita, K., Suzuki, G., Katsura, Y., Sado, T., Shimada, Y.
    • Journal Title

      Radiat.Res. 157

      Pages: 331-340

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Characteristic association of K-ras gene mutation with loss of heterozygosity in X-ray-induced thymic lymphomas of B6C3F1 mice.2001

    • Author(s)
      Yoshiya Shimada, et al.
    • Journal Title

      International Journal of Radiation Biology 77

      Pages: 465-473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 Scid mice.2001

    • Author(s)
      Mayumi Nishimura, et al.
    • Journal Title

      Mutation Research 486

      Pages: 275-283

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Single nucleotide instability without microsatellite instability in rat mammary carcinomas.2001

    • Author(s)
      Watanabe, N., Okochi, E., Y.Shimada, Y., Yanagihara, K., Yoshida, M., Takahashi, S., Mochizuki, M., Sugimura, T., Nagao, M., Ushijima, T
    • Journal Title

      Cancer Res. 61

      Pages: 2632-2640

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Characteristic association of K-ras gene mutation with loss of heterozygosity in X-ray-induced thymic lymphomas of B6C3F1 mice.2001

    • Author(s)
      Shimada, Y., Nishimura, M., Kakinuma, S., Ogiu, T., Suzuki, G., Nakata, Y., Sasanuma, S., Mita, K., Sado, T.
    • Journal Title

      Int.J.Radiat.Biol. 77

      Pages: 465-473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 Scid mice.2001

    • Author(s)
      Nishimura, M., Kakinuma, S., Wakana, S., Mita, K., Sado, T., Ogiu, T., Shimada, Y.
    • Journal Title

      Mutat.Res. 486

      Pages: 275-283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice.2001

    • Author(s)
      Nose, M., Uzawa, A., Ogiu, T., Suzuki, G.
    • Journal Title

      J.Radiat.Res. 42

      Pages: 191-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Absence of linkage between radiosensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat.2000

    • Author(s)
      Toshiaki Ogiu, et al.
    • Journal Title

      Radiation Research 154

      Pages: 113-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on chromosome 11 in murine thymic lymphomas.2000

    • Author(s)
      Yoshiya Shimada, et al.
    • Journal Title

      Radiation Research 154

      Pages: 293-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Absence of linkage between radio sensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat.2000

    • Author(s)
      Ogiu, T., Nishimura, M., Watanabe, F., Ukai, H., Ishii-Ohba, H., Shimada, Y., Tsuji, H., Sakurai, J., Hino, O.
    • Journal Title

      Radiat.Res. 154

      Pages: 113-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on chromosome 11 in murine thymic lymphomas.2000

    • Author(s)
      Shimada, Y., Nishimura, M., Kakinuma, S., Okumoto, M., Shiroishi, T., Clifton, K.H., Wakana, S.
    • Journal Title

      Radiat.Res. 154

      Pages: 293-300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Low frequency of ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of scid mice.1999

    • Author(s)
      Mayumi Nishimura, et al.
    • Journal Title

      Radiation Research 151

      Pages: 142-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Low frequency of ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of Scid mice.1999

    • Author(s)
      Nishimura, M., Wakana, S., Kakinuma, S., Mita, K., Ishii, H., Kobayashi, S., Ogiu, T., Sado, T., Shimada, Y.
    • Journal Title

      Radiat.Res. 151

      Pages: 142-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Journal Article] Increased sensitivity of scid heterozygous mice to ionizing radiation.1997

    • Author(s)
      Shigeru Kobayashi, et al.
    • Journal Title

      International Journal of Radiation Biology 72

      Pages: 537-545

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Book] Proceedings of International Symposium on Radiation and Homeostasis2002

    • Author(s)
      Toshiaki Ogiu, et al.
    • Publisher
      Elsevier Science, Netherlands (印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shigeru Kobayashi, et al.: "Increased sensitivity of scid heterozygous mice to ionizing radiation"International Journal of Radiation Biology. 72. 537-545 (1997)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mayumi Nishimura, et al.: "Low frequency of ras gene mutation in spontaneous and gamma-ray-indticed thymic lymphomas of scid mice"Radiation Research. 151. 142-149 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshiaki Ogiu, et al.: "Absence of linkage between radiosensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat"Radiation Research. 154. 113-116 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshiya Shimada, et al.: "Radiation-associated loss of heterozygosity at the Znfnlal (Ikaros)locus on chromosome 11 in murine thymic lymphomas"Radiation Research. 154. 293-300 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshiya Shimada, et al.: "Characteristic association of K-ras gene mutation with loss of heterozygositv in X-ray-induced thymic lymphomas of B6C3F1 mice"International Journal of Radiation Biology. 77. 465-473 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mayumi Nishimura, et al.: "Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 Scid mice"Mutation Research. 486. 275-283 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshiaki Ogiu, et al.: "Proceedings of International Symposium on Radiation and Homeostasis"Elsevier Science, Netherlands(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi,S.: "Increased sensitivity of scid heterozygous mice to ionizing radiation."Int.J.Radiat.Res.. 72. 537-545 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinebuchi,M.: "Deviated overexpression of TCR-β, TCR-γ, CD-4, and CD-8 on thymic lymphomas induced by 1-propyl-1-nitrosourea."Journal of Immunology. 159. 748-756 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,H.: "Comparison of tumorigenesis between accelerated haevy ion and X-rays in B6C3F1 mice."Journal of Radiation Research. 39. 93-100 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishimura,M.: "Low frequency of ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of scid mice."Radiation Research. 151. 142-149 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogiu,T.: "Absence of linkage between radiosensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat."Radiation Research. 154. 113-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimada,Y..: "Characteristic association of K-ras gene mutation with loss of heterozygosity in X-ray-induced thymic lymphomas of B6C3F1 mice."Int.J.Radiat.Res.. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogiu,T.: "Comparative Evaluation of Environmental Toxicants (ed.by J.Inaba and Y.Nakamura)"Kodansha Scientific Ltd.,Tokyo. 311 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogiu,T.: "Proceedings of the International Symposium on Biological Effects of Low Dose Radiation (ed.by F.Sato,Y.Yamada,J.Onodera)"Institute of Environmental Sciences, Aomori. 249 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi S.: "Increased sensitivity of scid heterozygous mice to ionizing radiation"Int.J.Radiat.Res.. 72. 537-545 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kinebuchi M.: "Deviated overexpression of TCR-β,TCR-γ,CD-4,and CD-8 on thymic lymphomas induced by 1-propyl-1-nitrosourea"Journal of Immunology. 159. 748-756 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe H.: "Comparison of tumorigenesis between accelerated haevy ion and X-rays in B6C3F1 mice"Journal of Radiation Research. 39. 93-100 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishimura M.: "Low frequency of ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of scid mice"Radiation Research. 151. 142-149 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 石井洋子: "Scidマウスの放射線感受性と発がん感受性"放射線科学. 42(Supple). 70-75 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogiu T.: "Absence of linkage between radiosensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat"Radiation Research. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogiu T.: "Comparative Evaluation of Environmental Toxicants (ed.by J.Inaba and Y.Nakamura)"Kodansha Scientific Ltd.,Tokyo. 311 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogiu T.: "Proceedings of the International Symposium on Biological Effects of Low Dose Radiation (ed.by F.Sato)"Institute of Environmental Sciences,Aomori(in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2021-11-25  

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