α-粒子诱发BEP2D细胞癌变系的DNA断裂重接修复缺陷与XRCCs修复基因mRNA表达研究  

The studies of DNA double-strand break (DSB) rejoining and mRNA expression of repair gene XRCCs in malignant transformed cell lines of human bronchial epithelial cells generated by α-particles

作　　者：孙敬芬[1] 隋建丽[1] 耿煜[1] 周平坤[1] 吴德昌 

机构地区：[1]北京放射医学研究所,100850

出　　处：《中华放射医学与防护杂志》2002年第6期405-408,共4页Chinese Journal of Radiological Medicine and Protection

基　　金："十五"军队医学杰出中青年基金资助项目 ( 0 1J0 0 6 ) ;国家高技术研究发展 86 3计划资助项目 (Z0 0 1AA2 2 12 71)

摘　　要：目的　研究α粒子诱发人支气管上皮细胞 (BEP2D)癌变细胞系BERP35T 1和BERP35T 4的DNA断裂损伤修复能力 ,分析其DNA断裂修复基因XRCCs系列的mRNA表达。方法脉冲电场凝胶电泳法检测DNA双链断裂 ,RT PCR分析DNA修复基因的mRNA表达。结果　恶性转化细胞系BERP35T 1和BERP35T 4受 0～ 15 0Gyγ射线照射后修复 4h的DNA断裂残留损伤显著高于亲本BEP2D细胞 ,mRNA表达分析显示修复基因XRCC2、XRCC3和Ku80 (XRCC5 )表达下调 2 5～6 5倍 ,而BERP35T 4细胞中DNA PKcs(XRCC7)表达上调 2 4倍。结论　α粒子诱发恶性转化细胞系的DNA链断裂修复机理缺陷 ,其中部分原因是DNA修复基因的表达抑制。DNA修复缺陷将导致细胞基因组不稳定性 ,α粒子诱发细胞恶性转化机理可能与此相关。Objective To investigate the efficiency of γ-ray-induced DNA DSB rejoining and the mRNA expression of DNA repair genes in malignantly transformed cell lines of human bronchial epithelial cells generated by exposure to α-particles. Methods Pulsed field gel electrophoresis (PFGE) was used to detect DNA.DSBs mRNA expression was analyzed by RT-PCR. Results The residual DNA DSB damage level after 4hrs repair following 0-150 Gy of γ-irradiation in the malignantly transformed cell lines BERP35T-1 and BERP35T-4 was significantly higher than that in their parental BEP2D cells.The analysis of mRNA level revealed a 2.5-to 6.5-fold down-regulated expression of the DNA repair genes XRCC-2,XRCC-3 and Ku80(XRCC-5) in BERP35T-1 and BERP35T-4 cells as compared with the parental BEP2D cells.In contrast,the expression of DNA-PKcs(XRCC7) was 2.4-fold up-regulated in the transformed cell line BERP35T-4,in which there was a significantly higher pro-portion of polyloid cells. Conclusion This study results show that the deficiency of DNA DSB rejoining and depressed mRNA expression of DNA repair genes could be involved in the malignant transformation process of BEP2D cells induced by exposure to α-particles. ;

关 键 词：α-粒子 BEP2D细胞 癌变 DNA断裂 DNA修复基因 mRNA表达 肺癌 

分 类 号：R734.2[医药卫生—肿瘤]