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1999 Fiscal Year Final Research Report Summary

Biological study on Prevention of Restenosis by Intra-arterial Irradiation

Research Project

Project/Area Number 10470193
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHIBUYA Hitoshi  Tokyo Medical and Dental Univ. Dept. Radiology, Professor, 医歯学総合研究科, 教授 (10014292)

Co-Investigator(Kenkyū-buntansha) FUKUDA Hozumi  Tokyo Med. and Dent. Univ. Dept. Radiology, Assistant Prof, 医歯学総合研究科, 助手 (60282753)
YOSHIMURA Ryoichi  Tokyo Med. and Dent. Univ. Dept. Radiology, Assistant Prof, 医歯学総合研究科, 助手 (40302864)
MIURA Masahiko  Tokyo Med. and Dent. Univ. Dept. Radiology, Assistant Prof, 歯学部, 助手 (10272600)
Project Period (FY) 1998 – 1999
Keywordsrestenosis / smooth muscle cells / PCNA / ionizing radiation
Research Abstract

The purpose of this study was to pursue the biological mechanisms by which ionizing radiation (IR) inhibits intimal hyperplasia after PTA. Since it is already known that growth inhibition of smooth muscle cells is a major factor of the phenomenon, we used primary cultured smooth muscle cells as a model. When cells were X-irradiated at a dose of 20 Gy, no apparent evidence of poptosis was obtained in terms of morphology at least up to 48h. None of enhanced expression of Fas or Fas-L, or activation of caspase-8 was observed following irradiation. Furthermore, cleavage of PKC-δ was not detected, indicating that apoptotic activities in smooth muscle cells following irradiation is quite low. It was thus suggested that apoptosis does not seem to be attributed to the IR-induced growth inhibition of smooth muscle cells. We found that PCNA-dependent DNA repair is functional in smooth muscle cells following X-irradiation and showed that another base excision repair (BER) pathway, pol β-dependent one, is not functional under the condition. These results strongly imply that PCNA-dependent DNA repair may be important to get apoptosis-refractory properties in smooth muscle cells. We also showed radiobiological properties of osteoradionercrosis (ORN) of the mandibular bone, which is caused by vessel damage in the bone, utilizing clinical data from pataients receiving Ir brachytherapy for oral tongue carcinoma. Cox proportional regression analysis revealed that biological effective dose (BED) using an α/β ratio for late responding tissues estimated at the surface of the lower lingual gum was the best prognosticator to predict ORN, and dose-response curves for ORN were obtained. These results provide useful information to analyze inhibitory effects of restenosis by intra-arterial irradiation.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Miura M.: "Biological response to ionizing radiation in mouse embryo fibroblasts with a targeted disruption of the DNA polymerase β gene"Radiation Research, in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura M.: "Differential effects of the insulin-like growth factor I receptor on radiosensitivity and spontaneous necrosis formation of human glioblastoma cells grown in spheroids"Experimental Cell Research. 250. 99-111 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura M.: "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair"Journal of Radiation Research. 40. 1-12 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura M.: "Factors affecting mandibular complications in low dose-rate brachytherapy for oral tongue carinoma with special reference to spacer"International Journal of Radiation Oncology, Biology, Physics. 41. 763-770 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura, M., Takeda, T., Sasaki, T., Inoue, T., Nakayama, T., Fukuda, H., Hoshi, A., Hoshina, M., and Shibuya, H.: "Factors affecting mandibular complications in low dose-rate brachytherapy for oral tongue carinoma with special reference to spacer."International Journal of Radiation Oncology, Biology, Physics. 41. 763-770 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura, M.: "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair."Journal of Radiation Research. 40. 1-12 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, H., Miura, M., and Sasaki, T.: "Differential effects of the insulin-like growth factor I receptor on radiosensitivity and spontaneous necrosis formation of human glioblastoma cells grown in spheroids."Experimental Cell Research. 250. 99-111 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura, M., Watanabe, H., Okochi, K., Sasaki, T., and Shibuya, H.: "Biological response to ionizing radiation in mouse embryo fibroblasts with a targeted disruption of the DNA polymerase β gene."Radiation Research. (in press). (2000)

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

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Published: 2001-10-23  

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