Riches A, Herceg Z, Wang H, Bryant P, Armitage M, Gamble S, Arrand J, O'Reilly S, Seymour C, Mothersill C
School of Biological and Medical Sciences, University of St. Andrews, Scotland, United Kingdom.
Radiat Oncol Investig. 1997;5(3):139-43. doi: 10.1002/(sici)1520-6823(1997)5:3<139::aid-roi11>3.0.co;2-1.
It has proved difficult to develop suitable models to study radiation-induced carcinogenesis by using human epithelial cells. However, immortalised human epithelial cell lines have proved useful. Unirradiated cells from the human keratinocyte cell line (HPV-G) and the human embryonic lung cell line (L132) were found to be tumourigenic in T-cell-deficient mice; thus, they are not suitable for transformation studies. Human urothelial cell lines (SV-HUC-1, NT11, BC16) and the human thyroid epithelial cell line (HTori-3) were nontumourigenic. The urothelial cell lines were refractory to radiation-induced carcinogenesis, and only one small tumour was observed in 57 mice that received irradiated cells. Whereas tumours were not produced following irradiation of these urothelial cells, changes in anchorage-independent growth were observed after a single dose of 8 Gy gamma-irradiation but not after 2 or 4 Gy. Irradiation of the human thyroid epithelial cell line (HTori-3) in vitro resulted in tumour formation. Passaging of the cells in vitro before injection did not seem to be critical. Some of the cell lines derived from the primary thyroid tumours exhibited p53 mutations in exons 5, 6, 7, and 8, as detected by single-stranded conformational polymorphism (SSCP) analysis. Thus, the human thyroid epithelial cell line (HTori-3) looks promising as a model for investigating the molecular events in radiation-induced carcinogenesis.
事实证明，利用人类上皮细胞开发合适的模型来研究辐射诱导的致癌作用是困难的。然而，永生化的人类上皮细胞系已被证明是有用的。人们发现，来自人类角质形成细胞系（HPV-G）和人类胚胎肺细胞系（L132）的未受辐射的细胞在T细胞缺陷小鼠中具有致瘤性；因此，它们不适合用于转化研究。人类尿路上皮细胞系（SV-HUC-1、NT11、BC16）和人类甲状腺上皮细胞系（HTori-3）不具有致瘤性。尿路上皮细胞系对辐射诱导的致癌作用具有抗性，在接受辐射细胞的57只小鼠中仅观察到一个小肿瘤。虽然这些尿路上皮细胞在辐射后未产生肿瘤，但在单次8 Gyγ射线照射后观察到了不依赖贴壁生长的变化，而在2 Gy或4 Gy照射后未观察到。体外照射人类甲状腺上皮细胞系（HTori-3）导致肿瘤形成。注射前在体外传代细胞似乎并不关键。通过单链构象多态性（SSCP）分析检测到，一些源自原发性甲状腺肿瘤的细胞系在第5、6、7和8外显子中存在p53突变。因此，人类甲状腺上皮细胞系（HTori-3）作为研究辐射诱导致癌作用中分子事件的模型看起来很有前景。
