Radiation-induced transformation of SV40-immortalized human thyroid epithelial cells by single and fractionated exposure to gamma-irradiation in vitro

Radiation-induced transformation of a human thyroid epithelial cell line (HTori-3) has been investigated following exposure to single and fractionated doses of gamma-irradiation. The human epithelial cells were irradiated in vitro and following passaging, transplanted to the athymic nude mouse. Following a single exposure to gamma-irradiation in the range 0.5-4 Gy, 22 tumours were observed in 45 recipients and following three equal fractions in the range 0.5-4 Gy per fraction, 18 tumours were observed in 31 recipients. Tumours were undifferentiated carcinomas and were observed from 7 to 20 weeks after transplantation. They occurred after similar radiation doses to those received by the children in the Belarus region of Ukraine, who developed thyroid tumours. The number of tumours observed, in each group receiving cells irradiated with a single dose of gamma-irradiation in the range 0.5-4 Gy, was similar. Cell lines were established from some tumours and the tumorigenicity confirmed by retransplantation. These tumour cell lines were more radiosensitive than the human thyroid epithelial cell line they were derived from. This indicates that transformed cells were not being selected from a subpopulation within the parent cell line but that radiation-induced transformants were being induced de novo. The human origin of the tumours was established by karyotyping, immunocytochemical demonstration of human epithelial cytokeratins and p53 analysis. DNA fingerprinting confirmed that the tumours were derived from the original cell line. Human epithelial cells have proved difficult to transform by exposure to radiation. This human thyroid epithelial cell line can be transformed by single and fractionated doses of gamma-irradiation and promises to be a useful model for studying the mechanisms of radiation-induced transformation of human epithelial cells.