六价铬致BEAS-2B细胞DNA损伤修复基因转录组学特征分析  

Transcriptome analysis character on Cr(Ⅵ) exposure related DNA repair genes

作　　者：哈飞再 郑湃[2] 冯慧敏 苏泽康 胡贵平 王天成[1] 贾光[2] HA Fei-zai;ZHENG Pai;FENG Hui-min;SU Ze-kang;HU Gui-ping;WANG Tian-cheng;JIA Guang(Department of Laboratory Medicine,Peking University Third Hospital,Beijing 100191,China;Department of Occupational and Environmental Health Science,School of Public Health,Peking University,Beijing 100091,China;School of Medical Science and Engineering,Beihang University,Beijing 100191,China)

机构地区：[1]北京大学第三医院检验科,北京100191 [2]北京大学公共卫生学院劳动与环境学系,北京100191 [3]北京航空航天大学医学科学与工程学院,北京100191

出　　处：《毒理学杂志》2021年第4期289-292,304,305,共6页Journal of Toxicology

基　　金：国家自然科学基金(81673118)。

摘　　要：目的研究六价铬暴露对细胞DNA损伤修复相关基因的影响。方法将人支气管上皮细胞系(BEAS-2B)暴露于0.20、0.60、1.80μmol/L六价铬24 h,提取RNA进行转录组学的测定。分析得到不同剂量组的差异表达mRNA并与AmiGO 2数据库进行比对,提取并分析DNA修复相关基因的差异表达、功能、互作网络及候选基因。结果六价铬染毒后共得到3959个差异基因,其中下调基因共有2928个,上调基因有1031个。在不同染毒剂量下,低、中和高染毒组各有506、981以及2472个差异基因。对提取的DNA修复相关基因分析的结果显示,SMC1A基因在3个剂量组中均差异表达;有11个基因在中、高剂量组中均差异表达,其中有3个基因参与DNA双链断裂的修复,分别为BRCA2、RAD51B和PRKDC,在高剂量组中与对照组差异表达的倍数分别为0.70(P=0.005)、0.19(P=0.003)和0.52(P=0.007);MGME1基因涉及线粒体DNA的修复,相对于对照组,中、高剂量组表达改变倍数为0.75(P<0.001)、0.67(P=0.025)。结论六价铬染毒后DNA部分修复基因表达发生了改变,其中DNA双链断裂修复相关基因BRCA2、RAD51B和线粒体DNA修复基因MGME1可作为进一步研究的候选基因。Objective To investigate the effect of Cr(Ⅵ)exposure on DNA repair related genes.Methods Human bronchial epithelial cell line(BEAS-2 B)cells were exposed to Cr(Ⅵ)at concentrations of 0.20,0.60,and 1.80μmol/L for 24 h.After extracting RNA,samples were set to the whole transcriptome sequencing.Differently expressed genes were compared with the AmiGO 2 database and genes with annotation of DNA repair were withdrawn for further analysis.The fold change,function of these DNA repair genes and constructed network to select candidate genes were all analyzed.Results A total of 3959 differentially expressed(DE)genes were identified,with 2928 up regulation genes and 1031 down regulation genes.There were 506981 and 2472 DE genes in low,middle and high dose group,respectively.The result of DNA repair related gene analysis showed that SMC1 A gene was differentially expressed in the three dose groups.There were 11 genes differentially expressed in the medium and high dose groups,among which three genes were involved in the repair of DNA double strand breaks,namely BRCA2,RAD51 B and PRKDC.The multiple of differential expression in the high dose group was 0.70(P=0.005),0.19(P=0.003)and 0.52(P=0.007)compared with the control group,respectively.MGME1 was involved in the progress of mitochondrial DNA repair,and the fold change in middle and high dose group were 0.75(P<0.001)and 0.67(P<0.025).Conclusion The expression of DNA repair genes changed after Cr(Ⅵ)exposure.The DNA double-strand break genes BRCA2,RAD51 B and the mitochondrial DNA repair gene MGME1 can be used as candidate genes for the repair mechanism research.

关 键 词：六价铬 DNA修复 DNA双链断裂 基因表达谱 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]