Development and analysis of human organ/tissue damage by fission radionuclides

1.用人体器官和组织(甲状腺、骨髓细胞、肺、胚胎组织)建立SCID小鼠模型2.裂变放射性核素对人体组织的影响：(1)测量了UTRKINKI(1W，最大剂量为10~7N/cm~2·秒)产生的裂变中子和γ射线在小鼠体内的剂量率，每小时0.2GY中子和0.2GYγ射线.(2)对11周龄Graves病患者移植的人甲状腺组织和人胚胎肺组织进行每周剂量0.2Gy射线照射6次和4次.在甲状腺和肺组织中未检测到P53、K-ras、c-Kit、β-catenin、Ret、Bak、Braf突变，而大剂量(11-33Gy137&gt；Cs)γ-射线在20例人甲状腺组织中诱发了8种突变(6种P53和2种c-Kit)。基因芯片分析(8500个基因)显示，中子(0.2Gy4)照射1周后，甲状腺组织的59.7个基因和肺组织的18.5个基因的基因表达增加或减少了4倍。3.给有人甲状腺组织的SCID小鼠每周给予~(131)&gt；I的作用：0.5MBq/只。暴露时间超过37周的18例甲状腺组织中有6例发生突变，而暴露时间在36周以下的24例甲状腺组织中仅有2例发生突变，7例P53突变和1例β-连环蛋白突变。单次剂量0.06-0.5MBq/只小鼠可诱导25-51.5个基因的基因表达增加或减少4倍，提示放射性碘的作用很强。4.在切尔诺贝利核电站灾难放射性核素暴露的清除者中，观察到WT1基因异常过表达，2人成为白血病。还检测了放射性核素接触者子女的微卫星突变。5.活性己糖相关化合物对γ射线诱发的先天性畸形和白血病有明显的抑制作用。

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.