| Project/Area Number |
15406010
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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 | 海外学術 |
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| Research Field |
Human pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
FUKUMOTO Manabu Tohoku University, Institute of Development, Aging & Cancer, Professor, 加齢医学研究所, 教授 (60156809)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Yuichi Cancer Institute, Department of Pathology, Senior Researcher, 癌研究所, 主任研究員 (80222975)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | radiation carcinogenesis / Plutonium / Thorotrast / internal exposure / human / angiosarcoma / mesothelioma / α-particles / 肝 |
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| Research Abstract |
A radiological contrast medium Thorotrast (Th) which contains a natural α-particle emitter, ThO_2 was used during World War II. After injection, Thorotrast deposited mainly in the liver and malignant liver tumors were induced by chronic exposure to α-particles. Relative risk of angiosarcoma (AS) is prominent and the frequency of intrahepatic cholangiocarcinoma (CCC) is also high in the patients with Thorotrast. The workers exposed to α-particles in plutonium (Pu) producing plant, Mayak of USSR were also suffered from AS and CCC in the liver. Pathological specimens of Mayak cases are kept in the South Ural Biophysics Institute (SUBI). Analysis of molecular mechanisms in Th- and Pu-induced liver tumors makes it possible to elucidate carcinogenic mechanisms of radiation in humans.
During the experimental term supported by this grant, we visited Russia twice and discussed once in Germany. Considering that SUBI is closed to the people outside, our success to have met them directly and borrow
… More
ed pathological specimen was epoch-making. We first tried to analyze genetic changes in Mayak cases but failed because of their storage conditions. Therefore, we made autoradiograms by exposing more than 6 months to confirm the distribution of α-particles on the histological sections. Almost all of the deposited Th was observed in macrophages whereas Pu was not seen. Th was apparently found both on the sections of AS and CCC from Th laden liver tissues, the number of 〓-tracks was higher in CCC cases than in AS cases. In MYAKAS, α-tracks were emited from parenchymal cells and leukocytes. The quantification of α-tracks and structural remodeling of the liver is underway to clarify their relationship. We found 3 cases of mesothelioma which were induced by extravasatiion of Th out of 238 cases of Th-induced tumors. During stay in SUBI we found 7 cases of malignant mesothlioma and brought back their pathological blocks to Japan. We are also collecting Asbestos-induced mesotheliomas in Japan. We are performing immunohistochemical analysis of SV40 virus particles and growth factors to elucidate radiation carcinogenesis in humans. Less
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