Zitzelsberger H, Bruch J, Smida J, Hieber L, Peddie C M, Bryant P E, Riches A C, Fung J, Weier H U, Bauchinger M
Institute of Radiobiology, GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Neuherberg, Germany.
Int J Cancer. 2001 Jun 20;96(3):166-77. doi: 10.1002/ijc.1015.
In vitro model cell systems are important tools for studying mechanisms of radiation-induced neoplastic transformation of human epithelial cells. In our study, the human thyroid epithelial cell line HTori-3 was analyzed cytogenetically following exposure to different doses of alpha- and gamma-irradiation and subsequent tumor formation in athymic nude mice. Combining results from G-banding, comparative genomic hybridization, and spectral karyotyping, chromosome abnormalities could be depicted in the parental line HTori-3 and in nine different HTori lines established from the developed tumors. A number of chromosomal aberrations were found to be characteristic for simian virus 40 immortalization and/or radiation-induced transformation of human thyroid epithelial cells. Common chromosomal changes in cell lines originating from different irradiation experiments were loss of 8q23 and 13cen-q21 as well as gain of 1q32-qter and 2q11.2-q14.1. By comparison of chromosomal aberrations in cell lines exhibiting a different tumorigenic behavior, cytogenetic markers important for the tumorigenic process were studied. It appeared that deletions on chromosomes 9q32-q34 and 7q21-q31 as well as an increased copy number of chromosome 20 were important for the tumorigenic phenotype. A comparative breakpoint analysis of the marker chromosomes found and those observed in radiation-induced childhood thyroid tumors from Belarus revealed a coincidence for a number of chromosome bands. Thus, the data support the usefulness of the established cell system as an in vitro model to study important steps during radiation-induced malignant transformation in human thyroid cells.
体外模型细胞系统是研究辐射诱导人上皮细胞发生肿瘤转化机制的重要工具。在我们的研究中，对人甲状腺上皮细胞系HTori-3进行了细胞遗传学分析，该细胞系先接受不同剂量的α射线和γ射线照射，随后在无胸腺裸鼠体内形成肿瘤。结合G显带、比较基因组杂交和光谱核型分析的结果，可以描绘出亲本细胞系HTori-3以及从所形成肿瘤中建立的9个不同HTori细胞系中的染色体异常情况。发现一些染色体畸变是猿猴病毒40永生化和/或辐射诱导人甲状腺上皮细胞转化的特征。源自不同辐射实验的细胞系中常见的染色体变化包括8q23和13cen-q21缺失以及1q32-qter和2q11.2-q14.1增加。通过比较具有不同致瘤行为的细胞系中的染色体畸变，研究了对致瘤过程重要的细胞遗传学标记。结果表明，9q32-q34和7q21-q31染色体缺失以及20号染色体拷贝数增加对致瘤表型很重要。对所发现的标记染色体与在白俄罗斯儿童辐射诱导甲状腺肿瘤中观察到的染色体进行比较断点分析，发现一些染色体带存在一致性。因此，这些数据支持所建立的细胞系统作为体外模型用于研究人甲状腺细胞辐射诱导恶性转化过程中重要步骤的有效性。
