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

1.人体器官/组织的长期维持：人甲状腺组织和骨髓细胞在改良的SCID(严重联合免疫缺陷)小鼠中长期保持(~3年)。人甲状腺组织的放射性损伤：对60岁左右的老年头颈部癌患者的正常甲状腺组织进行了3年的X射线照射。10~20Gy10~20Gy11例甲状腺组织中未发现k-ras、P53、c-Kit、β-catenin和Ret基因突变，24~65Gy11例甲状腺组织中有6例P53和c-Kit基因突变。(1)年龄敏感性：年轻Graves病患者(20岁)6~16Gy137&gt；Csγ照射后，有27.3%的甲状腺组织检测到P53和c-KIT基因突变。人甲状腺激素的分泌在9Gy射线照射和~(131)~(131)Gt；I(0.5MBq)照射后也受到明显抑制，提示辐射敏感性随年龄增加而增加。(2)剂量率效应：在高剂量率(1.1Gymin)下，11Gy以上的Graves病患者(20y)的11例人甲状腺组织中发生了6种p53和c-kit基因突变。然而，在低剂量率照射(0.4mGymin)后，未观察到突变，这表明在人甲状腺组织的辐射诱变中存在显著的剂量率效应。基因芯片对8,500个基因表达的改变也存在剂量率效应。(3)核辐射：原子辐射(0.2Gy中子+0.2Gy射线γ)诱导基因表达的改变。辐射引起的骨髓损伤：SCID小鼠受到致死剂量的γ射线(2Gy射线)照射后，可以通过静脉注射存活下来。注射人骨髓细胞。注射给SCID小鼠的人骨髓细胞随着γ剂量的增加而减少，如0、0.5、1和2Gy3个剂量组分别为38.0、37.3、25.4和2.7%。

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.