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氯化镉在Balb/c3T3细胞转化过程中对细胞凋亡的影响
Apoptosis induced by cadmium chloride during the early stage of transformation of Balb/c 3T3 cells
【摘要】 目的探讨氯化镉(CdCl2)在Balb/c 3T3细胞转化过程中对细胞凋亡的影响及其分子机制。方法N-甲基-N′-硝基-N-亚硝基胍(MNNG)启动后,CdCl2持续处理Balb/c 3T3细胞14 d,建立两阶段细胞转化模型。苔盼蓝排染法检测CdCl2的细胞毒性,AnnexinV-FITC/PI双染色结合流式细胞仪检测细胞凋亡率,小鼠毒理基因芯片检测CdCl2促癌作用过程中的基因表达变化。结果1 mg/L MNNG启动后,324μg/L CdCl2持续处理能诱导细胞转化灶的出现。CdCl2处理2 d后细胞存活率降低,凋亡率显著升高。同时基因表达谱分析筛选出的差异表达基因中,有11个基因的功能与细胞凋亡有关,10个基因的功能与细胞抗氧化机制有关。结论CdCl2在促癌过程能诱导Balb/c 3T3细胞凋亡,同时影响凋亡和抗氧化相关基因的表达。
【Abstract】 Objective To study the effects of cadmium chloride(CdCl2) on the apoptosis of Balb/c 3T3 cells during the tumor-promoting phase of two-stage cell transformation test,and to elucidate the involved gene expression changes.Methods Balb/c 3T3 cells were treated with N-methyl-N′-nitro-N-nitrosoguanidine(MNNG) as initiator and CdCl2 as promoter to generate the two-stage cell transformation model.The cytotoxicity of CdCl2 was measured by trypan blue exclusion assay,and the cellular apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry.The gene expression changes induced by CdCl2 during the tumor-promoting phase were determined by mouse toxicology gene chip analysis.Results After 1 mg/L MNNG initiated,324 μg/L CdCl2 could promote the transformation of Balb/c 3T3 cells.The cell viability was decreased and the percentage of apoptotic cells was increased significantly after CdCl2 treatment for 2 days.Additionally,in all differentially expressed genes induced by CdCl2,11 genes were related to apoptosis and 10 genes were related to antioxidation.Conclusion CdCl2 can induce apoptosis in Balb/c 3T3 cells during the tumor-promoting phase,and change the transcriptional expression of some genes related to apoptosis or antioxidation.
【Key words】 Apoptosis; Cell transformation; Balb/c 3T3; Cadmium chloride; Gene chip;
- 【文献出处】 毒理学杂志 ,Journal of Toxicology , 编辑部邮箱 ,2007年03期
- 【分类号】R730.2
- 【被引频次】2
- 【下载频次】147