EFFECT OF RADIATION EXPOSURE ON HUMAN ORGAN/TISSUE AND I'TS EXPERIMENTAL PROTECTION AND THERAPY

辐射暴露对人体器官/组织及其实验保护和治疗的影响

基本信息

批准号：
12308029
负责人：
NOMURA Taisei
金额：
$ 28.47万
依托单位：
OSAKA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12308029/
关键词：
radiation damage in human tissue improved SDID mice mouse with human tissues ^<137>Cs γ-rays radio-iodine mutation in human thyroid tissue human thyroid hormone GeneChip 137Csガンマ線ヒト甲状腺障害放射線ヨード超臨界事故

项目摘要

1. Long maintenance of human organ/tissue : Human thyroid tissues and bone marrow cells were maintained in the improved SCID (severe combined immunodeficient) mice for long period (〜3 years).2. Radiation-induced damage on human thyroid tissues: Normal thyroid tissues from old head and neck cancer patients (about 60 y) were exposed to X-rays for 3 years. No mutations were observed in k-ras, p53,c-kit,β-catenin and Ret genes after 10-20 Gy, but 6 mutations were detected in p53 and c-kit genes in 11 thyroid tissues after 24-65 Gy.(1) Age sensitivity: Mutations of p53 and c-kit genes were also observed in 27.3% of human thyroid tissues from young Graves' disease patient(20 y) after 6-16 Gy of ^<137>Cs γ-ray exposure. Secretion of human thyroid hormone was also inhibited significantly after 9 Gy exposure and ^<131>I(0.5 MBq), indicating higher radio-sensitivity at younger age.(2) Dose rate effect: Six mutations in p53 and c-kit genes were induced in 11 human thyroid tissues of Graves' disease patient (20 y) over 11 Gy at high dose rate (1.1 Gy/min). However, no mutations were observed following low dose rate exposure(0.4 mGy/min), suggesting significant dose rate effects in radiation mutagenesis in human thyroid tissues. Dose rate effects were also observed in the change of the expression of 8,500 genes by GeneChip.(3) Nuclear radiation : Atomic radiation(0.2 Gy neutron+0.2 Gy γ-rays) induced the change of gene expression.3. Radiation-induced bone marrow damage: SCID mice exposed to lethal doses of y -rays (2 Gy) can survive for life by i.v. injection of human bone marrow cells. Human bone-marrow cells injected to SCID mice decreased with higher doses of γ-rays,e.g.,38.0,37.3,25.4 and 2.7% at 0,0.5,1 and 2 Gy.

1。人体器官/组织的长期维持：长期（〜3年），人类甲状腺组织和骨髓细胞保持在改善的SCID（严重的合并免疫缺陷）小鼠中。2。辐射引起的对人甲状腺组织的损害：旧头颈癌患者（约60 Y）的正常甲状腺组织暴露于X射线3年。在10-20 Gy后K-RAS，p53，c-kit，β-catenin和ret基因中未观察到突变，但是在24-65 Gy（1）年龄敏感性后，在p53和c-kit敏感性的11个甲状腺组织中，在11个甲状腺组织中发现了6个突变：p53和C-Kit基因的突变：p53和C-Kit nory（p53和c-kit）的突变受到人类疾病的突变：27.3％的人（27.3％）在27.3％的患者中（27.3％）（27.3％）（27.3％）（27.3％）（27.3％''（27.3％） y）6-16 Gy ^<137> CSγ射线暴露。 9 Gy暴露和 ^<131> I（0.5 MBQ）的分泌也很明显地抑制，表明较小的无线电敏感性。（2）剂量率效应：p53和C-kit基因中的6种突变被诱发的11 G型患者（20 Y）Gy/min（gy）的11 Gy（1.2 y gy）诱导的p53和C-kit基因。然而，在低剂量率暴露（0.4 mgy/min）后未观察到突变，表明人甲状腺组织中辐射诱变的显着剂量率影响。还观察到剂量速率的效应在8,500基因的表达变化中。（3）核辐射：原子辐射（0.2 Gy中子+0.2Gyγ射线）诱导了基因表达的变化。3。辐射引起的骨髓损伤：暴露于致命剂量Y -rays（2 Gy）的SCID小鼠可以生存生命。注射人骨髓细胞。注射到SCID小鼠的人骨髓细胞随着较高剂量的γ射线降低，例如38.0,37.3,25.4和2.7％，在0,0.5,1和2 Gy时。