Project/Area Number |
16201013
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Risk sciences of radiation/Chemicals
|
Research Institution | Osaka University |
Principal Investigator |
NOMURA Taisei Osaka University, Graduate School of Medicine, Professor Emeritus, 名誉教授 (90089871)
|
Co-Investigator(Kenkyū-buntansha) |
HONGYO Tadashi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90271569)
NAKAJIMA Hiroo Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20237275)
OKA Yoshihiro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (20273691)
FUJIKAWA Kazuo Kinki University, Faculty of Science and Technology, Professor, 理工学部, 教授 (90247958)
ADACHI Shigeki National Institute of Biomedical Innovation, Designated Researcher, 特任研究員 (60379261)
梁 治子 大阪大学, 医学系研究科, 助手 (90301267)
|
Project Period (FY) |
2004 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥49,270,000 (Direct Cost: ¥37,900,000、Indirect Cost: ¥11,370,000)
Fiscal Year 2006: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2005: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2004: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
|
Keywords | fission radionuclides / mouse with human tissues / organ and tissue damage / mutation in human tissues / change in gene expression / functional damage / severe combined immuno-deficiency / radioactive iodine / 放射線ヨード / 放射線ヒト臓器・組織障害 / ヒト甲状腺ホルモン分泌能 |
Research Abstract |
1.Production of SCID mice with human organs and tissues (thyroid, bone marrow cells, lung, embryonic tissues) 2.Effects of fission radionuclides on human tissues. (1) Dose rate of fission neutron and γ-rays from UTR-KINKI (1W, max 10^7n/cm^2-.sec) in the mouse body was measured; 0.2 Gy neutron and 0.2 Gy γ-rays per hour. (2) Weekly doses of 0.2 Gy of neutron were given 6 times to the transplated human thyroid tissues from Graves' disease patients and also 4 times to the human lung tissues grown from embryonic lung at 11 weeks. No p53, K-ras, c-kit, β-catenin, RET, bak, BRAF mutations were detected by these doses in the thyroid and lung tissues, while large doses (11-33 Gy) of ^<137>Cs γ-rays induced 8 mutations (6 p53 and 2 c-kit) in 20 irradiated human thyroid tissues. GeneChip analyses (8500 genes) revealed 4 fold increases or decreases of gene expression in 59.7 genes of thyroid tissues and 18.5 genes of lung tissues 1 week after exposure to neutrons (0.2 Gy × 4). 3.Effects of ^<131>I : 0.5 MBq/mouse of ^<131>I was given weekly to SCID mice with human thyroid tissues. Six mutations were induced in 18 thyroid tissues exposed for more than 37 weeks, but only 2 mutations in 24 tissues for less than 36 weeks; 7 p53 and 1 β-catenin mutations. Single dose of 0.06-0.5 MBq/mouse of ^<131>I induced 4 fold increases or decreases in gene expression of 25-51.5 genes, suggesting very strong effects of radioiodine. 4.In the liquidators exposed to radionuclides from the catastrophe of Chernobyl nuclear plant, abnormal overexpression of WT1 gene was observed and 2 became leukemia. Microsatellite mutation was also examined in the children of liquidators exposed to radionuclides. 5.^<137>Cs γ-ray induced congenital malformation and leukemia were inhibited significantly by active hexose correlated compound.
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