Differential radiation sensitivity to morphological, functional and molecular changes of human thyroid tissues and bone marrow cells maintained in SCID mice

Morphology and function of human organs and tissues are well maintained in the improved SCID (severe
combined immunodeficient) mice for a long period (∼3 years). To study the radiation-induced damage on
human thyroid gland, human thyroid tissues transplanted to SCID mice were consecutively exposed to Xrays
or 137Cs -rays at high and low dose rates for approximately 2 years. Consecutive irradiation resulted
in the disappearance of follicles and significant decrease of thyroid hormone secretion. Mutations in p53
and c-kit genes were induced significantly in human thyroid tissues from old head and neck cancer patients
(av. 56.8 years, 4 males) and a Graves’ disease patient (20 years, male) over the dose of 24 Gy (44.7 ± 5.9 Gy,
mean ± S.E) and 11 Gy (20.2 ± 7.8 Gy), respectively, while mutations were not detected at lower doses nor
in unexposed matched controls (p < 0.01). There were significant differences in mutation frequency in the
transplanted human thyroid tissues (31 years, female) between high dose rate (1.19 Gy/min; 8 in 20 tissues)
and low dose rate (0.00023 Gy/min; 0 in 14 tissues) exposures (p < 0.01). Mutations were not detected in
RET, K-ras and ˇ-catenin genes. Expression analysis by GeneChip indicated that gene expression was also
well maintained in the transplanted human thyroid tissues. However, lower doses (1 or 3 Gy) of 137Cs -
rays can induce changes in gene expression in the transplanted human thyroid tissues. Furthermore, fatally
irradiated SCID mice could survive with human bone marrow cell transplantation. When about half of
mouse bone marrows were replaced by human bone marrow cells, the human bone marrow cells showed
high sensitivity to -irradiation; 28.0% and 0.45% survival after 0.5 and 2.0 Gy exposures, respectively