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低剂量α粒子辐射可改变人MCF-7乳腺癌细胞中调节细胞凋亡的基因表达。

Low doses of alpha particle irradiation modify the expression of genes regulating apoptosis in human MCF-7 breast cancer cells.

作者信息

Soto Jesús, Sainz Carlos, González-Lamuño Domingo, Cos Samuel

机构信息

Department of Medical Physics, School of Medicine, University of Cantabria, 39011 Santander, Spain.

出版信息

Oncol Rep. 2006 Mar;15(3):577-81.

Abstract

The possibility of modifying apoptosis-related genes in tumor cells is an interesting line of research that calls for multidisciplinary experimentation to describe its characteristics and the conditions required. In vitro low doses of alpha particle irradiation due to radon have an antiproliferative effect on the growth of MCF-7 cells and increase the sensibility of cancer cells to taxol, a chemotherapeutic agent that induces cellular apoptosis. The present study examines the in vitro effects of low doses of alpha particle irradiation from the gas radon on the expression of some bcl-2 family apoptosis-related genes. The analyzed genes were bax, bcl-2 and bcl-x, with known responses to genotoxic stress (bcl-2) or ionising radiation (bax and bcl-x) in MCF-7 human breast cancer cells. The results obtained indicate that the cell line studied expresses the mentioned genes and they demonstrate that irradiation with low radon doses of MCF-7 cells induces underexpression of both bax and bcl-2 genes. Interestingly, the mRNA levels of the full-length bcl-x gene (bcl-xL) were overexpressed after irradiation, and we found significant mRNA levels of an alternative mRNA splicing form of the same gene (bcl-xS), which enhances the apoptotic sensitivity of the cell. The increased sensitivity to apoptosis resulting from bcl-xS overexpression is important because it might improve the efficacy of chemotherapeutic agents used to treat cancers which act through induction of apoptosis. The finding that low radiation doses of alpha particles from the gas radon modulate the expression of apoptosis-related genes suggests a therapeutic utility for this naturally occurring agent.

摘要

改变肿瘤细胞中与细胞凋亡相关基因的可能性是一个有趣的研究方向,这需要多学科实验来描述其特征和所需条件。体外低剂量氡致α粒子辐射对MCF-7细胞的生长具有抗增殖作用,并增加癌细胞对紫杉醇(一种诱导细胞凋亡的化疗药物)的敏感性。本研究检测了低剂量氡气α粒子辐射对一些bcl-2家族细胞凋亡相关基因表达的体外影响。所分析的基因是bax、bcl-2和bcl-x,它们在MCF-7人乳腺癌细胞中对遗传毒性应激(bcl-2)或电离辐射(bax和bcl-x)有已知反应。获得的结果表明,所研究的细胞系表达上述基因,并且结果表明低剂量氡辐射MCF-7细胞会导致bax和bcl-2基因的表达下调。有趣的是,全长bcl-x基因(bcl-xL)的mRNA水平在辐射后过表达,并且我们发现同一基因的一种选择性mRNA剪接形式(bcl-xS)有显著的mRNA水平,它增强了细胞的凋亡敏感性。bcl-xS过表达导致的对细胞凋亡敏感性增加很重要,因为它可能会提高用于治疗通过诱导细胞凋亡起作用的癌症的化疗药物的疗效。低剂量氡气α粒子辐射调节细胞凋亡相关基因表达这一发现表明这种天然存在的物质具有治疗用途。

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