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

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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.