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Radiation-induced gene expression in MCF-7 cells.

机译:辐射诱导的MCF-7细胞中的基因表达。

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PURPOSE: Detection of gene targets applicable to biological dosimetry and early detection of radiation-induced cell damage. MATERIALS AND METHODS: MCF-7 human mammary carcinoma cells were exposed to 2 and 6 Gy X-rays. Expression of 1176 genes was traced with the Atlas Human 1.2 Array (Clontech). RESULTS: (1) Based on data reproducibility (about 98%), a new and improved analysis was employed. (2) Normalization of data using ubiquitin or total gene expression led to the same results. (3) Dose-dependent gene expression was shown for six genes, which were constantly expressed over 1 day (three genes), 2 days (two) and 3 days (one). Differential gene expression was confirmed by RTQ-PCR. Three of the six genes were novel radiation-induced gene targets. (4) When analysing the expression of all genes, the processes of cell degradation (e.g. cell death and protein catabolism) were activated. Simultaneously, inhibition not only of cell proliferation, but also of other cellular functions (e.g. cell repair) was found. Hence, cell death appears a process of 'active silencing'. CONCLUSIONS: With the screening method applied, six radiation-induced gene targets were found, three of which were novel genes. Their applicability in other cell models remains to be tested. Different sets of genes have to be considered for dose assessment, owing to their changes in gene expression with time after irradiation. Furthermore, it has to be investigated whether 'active silencing' represents a general principle of radiation-induced cell death.
机译:目的:检测适用于生物剂量学的基因靶标,以及及早发现辐射引起的细胞损伤。材料与方法:将人乳腺癌MCF-7细胞暴露于2和6 Gy X射线。用Atlas Human 1.2 Array(Clontech)追踪了1176个基因的表达。结果:(1)基于数据可重复性(约98%),采用了一种新的和改进的分析方法。 (2)使用泛素或总基因表达对数据进行归一化得到相同的结果。 (3)显示了六个基因的剂量依赖性基因表达,它们在1天(三个基因),2天(两个)和3天(一个)中持续表达。通过RTQ-PCR确认差异基因表达。六个基因中的三个是新的辐射诱导基因靶标。 (4)当分析所有基因的表达时,激活了细胞降解过程(例如细胞死亡和蛋白质分解代谢)。同时,发现不仅抑制细胞增殖,而且抑制其他细胞功能(例如细胞修复)。因此,细胞死亡似乎是“主动沉默”的过程。结论:采用筛选方法,发现了六个辐射诱导的基因靶标,其中三个是新基因。它们在其他细胞模型中的适用性还有待测试。由于辐射后基因表达随时间的变化,因此必须考虑使用不同的基因组进行剂量评估。此外,还必须研究“主动沉默”是否代表了辐射诱导的细胞死亡的一般原理。

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