Riches A C, Herceg Z, Bryant P E, Wynford-Thomas D
School of Biological and Medical Sciences, University of St Andrews, Fife, UK.
Int J Radiat Biol. 1994 Dec;66(6):757-65.
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.
在对人甲状腺上皮细胞系（HTori - 3）进行单次和分次γ射线照射后，对辐射诱导的细胞转化进行了研究。将人上皮细胞在体外进行照射，传代后移植到无胸腺裸鼠体内。单次暴露于0.5 - 4 Gy范围内的γ射线后，在45只受体中观察到22个肿瘤；在每次分次剂量为0.5 - 4 Gy且共分三次照射后，在31只受体中观察到18个肿瘤。肿瘤为未分化癌，在移植后7至20周出现。它们是在与乌克兰白俄罗斯地区患甲状腺肿瘤的儿童所接受的辐射剂量相似的情况下发生的。在接受0.5 - 4 Gy范围内单次γ射线照射的每组细胞中观察到的肿瘤数量相似。从一些肿瘤中建立了细胞系，并通过再次移植证实了其致瘤性。这些肿瘤细胞系比它们所源自的人甲状腺上皮细胞系对辐射更敏感。这表明转化细胞并非从亲代细胞系中的亚群中挑选出来，而是辐射诱导的转化体是从头诱导产生的。通过核型分析、人上皮细胞角蛋白的免疫细胞化学证明以及p53分析确定了肿瘤的人类起源。DNA指纹图谱证实肿瘤源自原始细胞系。已证明人上皮细胞难以通过辐射暴露实现转化。这个人甲状腺上皮细胞系可通过单次和分次γ射线照射实现转化，有望成为研究人上皮细胞辐射诱导转化机制的有用模型。
