| Project/Area Number |
10470193
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SHIBUYA Hitoshi Tokyo Medical and Dental Univ. Dept. Radiology, Professor, 医歯学総合研究科, 教授 (10014292)
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| 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)
姫野 佳郎 東京医科歯科大学, 医学部, 助手 (50238325)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | restenosis / smooth muscle cells / PCNA / ionizing radiation / smooth muscle cell |
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| 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.
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