PCB153对人B淋巴母细胞基因表达谱的影响  

Effects of PCB153 on gene expression profiles of human B lymphoblastoid cells

作　　者：宋鹏[1] 金凌之[1] 楼建林[1] 高明[1] 谭玉凤[1] 宋杨[1] 王禹[1] 刘克澄[1] 吴南翔[1] 

机构地区：[1]浙江省医学科学院卫生学研究所,浙江杭州310013

出　　处：《环境与健康杂志》2013年第1期27-31,共5页Journal of Environment and Health

基　　金：浙江省科技厅重大专项(2008C03001-1;2007C30015)

摘　　要：目的研究2,2’,4,4’,5,5’-六氯联苯(2,2’,4,4’,5,5’-hexachlorobiphenyl,PCB153)对人B淋巴母细胞基因表达谱的影响。方法采用0(对照)和25、100、200μmol/L的PCB153分别处理人B淋巴母细胞2、24、48 h,收集细胞后提取总RNA。PCB153处理24 h的RNA样本用Illumina人HT-12 v4全基因组表达谱芯片筛测差异表达基因,并对差异基因进行基因本体论(gene ontology,GO)分类分析。在PCB153处理2、24、48 h样本中用实时定量PCR对候选差异基因进行验证。结果芯片结果显示,各剂量PCB153处理样本中分别发现161、191、1 006个差异基因,三个剂量组重叠差异基因数为15个,其中,上调基因4个、下调基因11个。选取6个差异基因用定量PCR进行验证,发现2个上调基因(CCDC92和TMEM175)及3个下调基因(CCL22、STK38L和GZMK)的表达改变与芯片结果一致。基因CCDC92、CCL22、GZMK和TMEM175等可影响多种淋巴细胞功能,基因STK38L可作用于细胞周期和细胞凋亡等,基因CCL22和MTDH的异常表达则与多种癌症密切相关。结论体外急性染毒PCB153干扰了人B淋巴母细胞某些重要功能基因的表达,为多氯联苯毒性的分子作用机制提供了依据。Objective To study the effects of PCB153 on gene expression profiles of human B lymphoblastoid cells. Methods The ceils were harvested and total RNA was isolated after being exposed to PCB153 （0,25,100,200 txmol/L） for 2,24,48 h. Human HT-12 v4 of Illumina Bead Chip was applied to scan differentially expressed genes in 24 h treatment group. Gene ontology （GO） analysis was used to analyze the function of those differentially expressed genes. Quantitative PCR was used to validate the differential expression of candidate genes in all three treatment groups. Results A total of 161,191 and 1 006 differentially expressed genes were found in samples treated with low,morate and high concentrations of PCB153, respectively. There were an overlap of 15 differentially expressed genes among three treatment groups,with four genes up- regulated and 11 genes down-regulated. Six genes of them were selected for validating their expressions with quantitative PCR. The expressions of CCDC92 and TMEM175 genes were up-regulated while the expressions of CCL22 ,STK38L and GZMK were down-regulated,which were consistent with the results of microarray. CCDC92,CCL22,GZMK and TMEM175 genes might affect the function of various kinds of lymphocytes, and STK38 genes played an important role in cell cycle regulation and cell apoptosis,and the abnormal expression of CCL22 or MTDH genes was closely associated with many kinds of cancers. Conclusion PCB153 may disturb the expressions of some important genes in human B lymphoblastoid cells in vitro,which will contribute to the molecular mechanism underlying the toxicity of PCBs.

关 键 词：2 2' 4 4' 5' 5'-六氯联苯 人B淋巴母细胞系 基因芯片 

分 类 号：R994.6[医药卫生—毒理学]