Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Viral Vector Facility, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Mol Cancer Res. 2019 Apr;17(4):937-948. doi: 10.1158/1541-7786.MCR-18-0938. Epub 2019 Jan 16.
Radiation is used in multiple procedures as a therapeutic and diagnostic tool. However, ionizing radiation can induce mutations in the DNA of irradiated cells, which can promote tumorigenesis. As malignant transformation is a process that takes many years, there are intermediate stages of cells that have initiated the process but have not yet evolved into cancer. The study here aimed to investigate the effect of ionizing radiation on normal and partially transformed human mammary epithelial cells. Breast primary epithelial cells were derived from normal breast tissue from two different donors and modified by transduction with the SV40 small and large T antigen and genes to obtain partially transformed cells and also with to completely and experimentally transform them. After exposure to different doses of ionizing radiation, oncogenic features were analyzed by means of an anchorage-independent growth assay and 3D cell culture. The addition of radiation exposure resulted in an increase in the number and size of colonies formed in each of the conditions analyzed and in the reduction of the capacity of partially transformed cells to form properly polarized 3D structures. Moreover, partially transformed cells require lower doses of radiation than healthy cells to enhance anchorage-independent growth capacity. Although cells from different donors have a different degree of sensitivity in the response to radiation, a higher sensitivity to the radiation-induced cell transformation process was observed in those cells that had already initiated the oncogenic process, which require higher doses of radiation to complete the transformation process. IMPLICATIONS: Individuals carrying accumulation of genetic alterations may have an increased susceptibility to radiation-induced neoplastic transformation.
辐射被广泛应用于多种治疗和诊断程序中。然而，电离辐射会导致受照射细胞的 DNA 突变，从而促进肿瘤发生。由于恶性转化是一个需要多年时间的过程，因此存在已经启动但尚未发展为癌症的细胞中间阶段。本研究旨在探讨电离辐射对正常和部分转化的人乳腺上皮细胞的影响。乳腺原代上皮细胞源自两位不同供体的正常乳腺组织，通过转导 SV40 小和大 T 抗原以及 基因来获得部分转化细胞，并通过转导 基因使其完全和实验性转化。在暴露于不同剂量的电离辐射后，通过非依赖性生长测定和 3D 细胞培养分析致癌特征。在分析的每种条件下，添加辐射暴露会导致形成的菌落数量和大小增加，并且部分转化细胞形成适当极化 3D 结构的能力降低。此外，部分转化细胞比健康细胞需要更低剂量的辐射来增强非依赖性生长能力。尽管来自不同供体的细胞在对辐射的反应中具有不同的敏感性，但在已经启动致癌过程的细胞中观察到对辐射诱导的细胞转化过程更高的敏感性，这些细胞需要更高剂量的辐射来完成转化过程。意义：携带遗传改变积累的个体可能对辐射诱导的肿瘤转化具有更高的易感性。
