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 li ne (HTori-3) has been investigated following exposure to single and fr actionated doses of gamma-irradiation. The human epithelial cells were irradiated in vitro and following passaging, transplanted to the athy mic nude mouse. Following a single exposure to gamma-irradiation in th e range 0.5-4 Gy, 22 tumours were observed in 45 recipients and follow ing three equal fractions in the range 0.5-4 Gy per fraction, 18 tumou rs were observed in 31 recipients. Tumours were undifferentiated carci nomas and were observed from 7 to 20 weeks after transplantation. They occurred after similar radiation doses to those received by the child ren in the Belarus region of Ukraine, who developed thyroid tumours. T he number of tumours observed, in each group receiving cells irradiate d with a single dose of gamma-irradiation in the range 0.5-4:Gy, was s imilar. Cell lines were established from some tumours and the tumorige nicity confirmed by retransplantation. These tumour cell lines were mo re radiosensitive than the human thyroid epithelial cell line they wer e derived from. This indicates that transformed cells were not being s elected from a subpopulation within the parent cell line but that radi ation-induced transformants were being induced de novo. The human orig in of the tumours was established by karyotyping, immunocytochemical d emonstration of human epithelial cytokeratins and p53 analysis. DNA fi ngerprinting 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 epi thelial 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 radia tion-induced transformation of human epithelial cells.