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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/组织的长期保存：将人甲状腺组织和骨髓细胞长期保存在改良的严重联合免疫缺陷（SCID）小鼠体内（约3年）.人甲状腺组织的辐射损伤：对老年头颈癌患者（约60岁）的正常甲状腺组织进行了3年的X射线照射。10-20戈伊照射后，未发现k-ras、p53、c-kit、β-catenin和Ret基因突变，而24-65戈伊照射后，11例甲状腺组织中有6例p53和c-kit基因突变。(1)年龄敏感性：在6-16戈伊~（60）Gy ~（60 Gy）<137>在9戈伊照射和1 μ I（0.5 MBq）照射后，人甲状腺激素的分泌也受到显著抑制<131>，表明年轻时放射敏感性较高。(2)剂量率效应：在戈伊/min高剂量率照射下，11戈伊20岁Graves病患者甲状腺组织中有6例发生p53和c-kit基因突变。然而，在低剂量率暴露（0.4 mGy/min）后未观察到突变，这表明人类甲状腺组织中的辐射诱变具有显著的剂量率效应。在基因芯片检测的8,500个基因的表达变化中也观察到了剂量率效应。(3)核辐射：原子辐射（0.2戈伊+0.2戈伊射线）引起基因表达的改变.辐射诱导的骨髓损伤：暴露于致死剂量的γ射线（2戈伊）的SCID小鼠可以通过静脉注射人骨髓细胞而终身存活。注射到SCID小鼠的人骨髓细胞随着γ射线剂量的增加而减少，例如，0、0.5、1、2戈伊组分别为38.0、37.3、25.4、2.7%。