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

作　　者：敖琳[1] 高利宏[1] 胡冉[1] 杨梦苏[2] 曾志雄[2] 方志俊[2] 曹佳[1] 

机构地区：[1]第三军医大学预防医学院卫生毒理学教研室,重庆400038 [2]香港城市大学基因组科技应用研究中心

出　　处：《毒理学杂志》2007年第3期165-168,共4页Journal of Toxicology

基　　金：国家杰出青年基金资助项目(30125037);国家自然科学基金资助项目(30271136);国家973课题分题(2002CB512901)

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。Objective To study the effects of cadmium chloride （ CdCl2 ） on the apoptosis of Balb/c 3T3 cells during the tumorpromoting 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, 324μg/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.

关 键 词：细胞凋亡 细胞转化 BALB/C 3T3细胞 氯化镉 基因芯片 

分 类 号：R99[医药卫生—毒理学]