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1997 Fiscal Year Final Research Report Summary

Relationship between DNA Repair and Carcinogenesis in Radiosensitive Mutant Mice

Research Project

Project/Area Number 07670263
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OGIU Toshiaki  The 5th Research Group, Supervising Researcher, 第5研究グループ, 総合研究官 (40106183)

Co-Investigator(Kenkyū-buntansha) WATANABE Fumiaki  The 5th Research Group, National Institute, Post Doctoral Fellow, 第5研究グループ, 科学技術特別研究員
NISHIMURA Mayumi  The 5th Research Group, Researcher, 第5研究グループ, 研究員
SHIMADA Yoshiya  The 5th Research Group, Senior Researcher, 第5研究グループ, 主任研究官 (10201550)
ISHII Hiroko (OHBA Hiroko)  The 5th Research Group, Senior Researcher, 第5研究グループ, 主任研究官 (70159672)
Project Period (FY) 1995 – 1997
Keywordsscid Mice / Immunodeficiency / Radiosensitivity / DNA repair / Radiation carcinogenesis / Susceptibility for tumor development / Thymic lymphoma / DNA-dependent protein kinase
Research Abstract

Severe combined immunodeficient (scid) mice are known to be radiosensitive due to their heritable defects of repair of double strand breaks induced by ionizing radiation. We studied the effects of scid mutation on the acute as well as late effects of radiation. Acute 50% lethal dose of gamma-rays for scid, Fl and C.B-17 mice was 4.1,6.5 and 7.1 Gy, respectively. When mice were irradiated with same dose, survival period of Fl mice was shorter than that of C.B-17 mice. The bone marrow cells of scid mice were also radiosensitive as compared to those from other 2 strains. Bone marrow cells from Fl mice were slightly but significantly more radiosensitive than that from C.B-17 mice. These results mean that scid hetrozygotes are more resistant to ionizing radiation when compared with scid homozygotes, but more sensitive than wild-type. In late effect studies, groups of scid, Fl and C.B-17 mice were exposed to a single whole body dose of 1-3 Gy of gamma-rays. Results clearly indicated that scid mice were extremely susceptible for induction of thymic lymphomas as compared to other 2 strains. No difference for induction of thymic lymphomas was observed between Fl mice and C.B-17 mice. Ethyl-nitrosourea, a strong lymphomagen, was administered to scid mice. However, incidence of thymic lymphomas were not so high. These results indicate that close relationship between radiosensitivity and susceptibility for radiogenic development of thymic lymphomas was proved, but effect of scid heterozygosity was not demonstrated. Almost all thymic lymphomas of scid mice were CD4/CD8 double positive. In other organs, relationship between radiosensitivity and susceptibility for tumor development was not demonstrated in this system. Further studies are needed to analyze the effects of scid mutation radiation-induced development of solid tumors.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kubota、Y.: "Reduced fidelity of DNA synthesis in cell extracts from chemically induced primary thymic lymphomas of mice." Cancer Res.55. 3777-3780 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inano, H.: "Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats" J.Steroid Biochem.Molec.Biol.54. 47-53 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogiu, T.: "Genetic regulation of development of thymic lymphomas induced by N-propyl-N-nitrosourea in the rat" Japanese Journal of Cancer Research. 86. 638-644 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suwa, A.: "Autoantibodies to DNA-dependent protein kinase:Probes for the catalytic subunit" J.Clin.Invest.97. 1417-1421 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teraoka, H.: "CPP32/Yama/apopain cleaves the catalytic component of DNA dependent protein kinase in the holoenzyme" FEBS Letters. 393. 1-6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi, S.: "Comparison of dose-dependent enhancing effects of γ-ray irradiation on urethen-induced lung tumorigenesis in athymic nude(un/nu)mice and euthymic(nu/+)littermates" Journal of Cancer Research and Clinical Oncology. 122. 231-236 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimada, Y.: "Heterogneous aging of macrophage-lineage cells in the capacity for TNF production and self renewal in C57/BL/6 mice" Mechanism of Aging and Development. 87. 183-195 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagasawa, M.: "Nuclear translocation of the catalytic component of DNA-dependent protein kinase upon growth stimulation in normal human Tlymphocytes" Cell Stracture and Function. 22. 585-594 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chibazakura, T.: "Phospholylation of human general transcription factors TATA-binding protein and transcription factor IIB by DNA-dependent protein kinase synergistic stimulation of RNA polymerase" Eur.J.Biochem.247. 1166-1173 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi, S.: "Increased sensitivity of scid heterozygous mice to ionizing radiation" International Journal of Radiation Biology. 72. 537-545 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, H.: "Comparison of tumorigenesis between accelerated heavy ions and X-rays in B6C3F1 mice" Journal of Radiation Research. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogiu, T.: "Text Book of Human-Radiation Interface" National Institute of Radiological Sciences, 381 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogiu, T.: "Proceedings of the International Workshop on Comparative Evaluation of Health Effects of Environmental Toxicants derived from Advanced Technology" National Institute of Rediological Sciences(in press), (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kubota Y., Murakami-Murofushi, K., Shimada, Y., Ogiu, T,Oikawa, T.: "Reduced fidelity of DNA synthesis in cell extracts from chemically induced primary thymic lymphomas of mice." Cancer Res.55. 3777-3780 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inano, H., Ishii-Ohba, H., Suzuki, K., Yamanouchi, H., Onoda, M., Wakabayashi, K.: "Chemoprevention by dietary dehydroepiandro-sterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats." J.Steroid Biochem.Mlec.Biol.54. 47-53 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogiu, T., Fukami, H., Nishimura, M., Matsuyama, M.: "Genetic regulation of development of thymic lymphomas induced by N-propyl-N-nitrosourea in the rat." Jpn.J.Cancer Res.86. 638-644 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suwa, A., Hrakata, M., Takeda, Y., Okano, Y., Mimori, T., Inada, S., Watanabe, F., Teraoka, H., Dynan, W.S., Hardin, J.A.: "Autoantibodies to DNA-dependent protein kinase : Probes for the catalytic subunit." J.Clin.Invest.97. 1417-1421 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teraoka, H., Yumoto, Y., Watanabe, F., Tsukada, K., Suwa, A., Enari, M., Nagata, S.: "CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme." FEBS Letters. 393. 1-6 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayshi, S., Otsu, H., Noda, Y., Ogiu, T.: "Comparison of dose-dependent enhancing effects of gamma-ray irradiation on urethan-induced lung tumorigenesis in athymic nude (nu/nu) mice and euthymic (nu/ ; ) littermates." J.Cancer Res.Clin.Oncol.122. 231-236 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimada, Y., Ito, H.: "Heterogenous aging of macrophage-lineage cells in the capacity for TNF production and self renewal in C57/BL/6 mice." Mech.Ageing Develop.87. 183-195 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagasawa, M., Watanabe F., Suwa, A., Yamamoto, K., Tsukada, K., Teraoka, H.: "Nuclear translocation of the catalytic component of DNA-dependent protein kinase upon growth stimulation in normal human T lymphocytes." Cell Stracture and Function. 22. 585-594 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chibazakura, T., Watanabe, F., Kitajima, S., Tsukada, K., Yasukouchi, Y., Teraoka, H.: "Phospholylation of human general transcription factors TATA-binding protein and transcription factor IIB by DNA-dependent protein kinase synergistic stimulation of RNA polymerase II basal transcription in vitro." Eur.J.Biochem.247. 1166-1173 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kinebuchi, M., Matsuura, A., Ogiu, T., Kikuchi, K.: "Deviated overexpression of TCR-beta, TCR-gamma, CD-4, and CD-8 on thymic lymphomas induced by 1-propyl-1-nitrosourea." J.Immunol.159. 748-756 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, S., Nishimura, M., Shimada, Y., Suzuki, F., Matsuoka, A., Sakamoto, H., Hayashi, M., Sofuni, T., Sado, T., Ogiu, T.: "Increased sensitivity of scid heterozygous mice to ionizing radiation." Int.J.Radiat.Res.72. 537-545 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, H., Ogiu, T., Nishimura, M., Masaoka, Y., Kurosumi, M., Takahashi, T., Oguri, T., Shoji, S., Katoh, O.: "Comparison of tumorigenesis between accelerated haevy ions and X-rays in B6C3F1 mice." J.Radiat.Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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