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

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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.