TRF1和TRF2在砷致MGC803细胞染色体畸变中的作用

Role of TRF1, TRF2 in Chromosomal Aberrance of MGC803 Cells Induced by Arsenic

为了分析端粒重复序列结合因1和2(TRF1和TRF2)在砷致MGC803细胞染色体畸变中的作用,探讨砷致细胞增殖及癌变的可能机制,以人MGC803细胞为实验对象,采用染色体分析检测畸变率及有丝分裂指数(MI)、Western印迹检测TRF1、TRF2、PCNA表达。结果表明,0.625μmol/LAs2O3处理MGC803细胞4周后,PCNA表达及有丝分裂指数均高于对照组,显示细胞分裂增殖增强;染色体分析显示畸变率明显高于对照组,畸变类型以融合染色体(即双或多着丝粒、环形染色体)为主;同时,Western印迹分析结果表明TRF1表达上升,而TRF2表达下降。研究结果提示低浓度砷通过上调TRF1表达和下调TRF2表达,导致染色体畸变率增加以及基因组稳定性下降,从而加快细胞增殖。

The purpose of this experiment is to investigate the role of telomeric repeat binding factorl, 2 （TRF1, TRF2） in the process of chromosomal aberrance of MGC803 cells induced by arsenic, and to explore the possible mechanism of cell proliferation and carcinogenesis induced by arsenic. Human gastric cancer MGC803 cells were used in the experiments, the aberrated rate and mitotic index of MGC803 cells were detected by chromosomal analysis. Expression of TRF1, TRF2 and PCNA were detected by Western blot. Both mitotic index and expression of PCNA in MGC803 cells exposure to 0.625 μtmol/L As2O3 for 4 week were higher than that of the controls. Chromosomal analysis indicated that the aberrance rates of MGC803 cells were significantly higher than that of the controls, and the most type of aberrances was chromosomal fusion （double or multi-centromere, ringed chromosome）. Western blot analysis showed the expression of TRF1 was up-regulated while TRF2 was downregulated. The present results suggest that the up-regulation of TRF1 and down-regulation of TRF2 could increased chromosomal aberration rate and genome instability in MGC803 cells by long-term exposure to low concentration arsenic.