MNNG诱导的DNA损伤对人肺癌H1299细胞中FOXO1亚细胞定位的影响  

The subcellular transportation of FOXO1 responds to DNA damage induced by MNNG in human lung cancer cells

作　　者：徐韬钧[1] 张洪开[1] 肖莎[1] 于爱鸣[1] 

机构地区：[1]中国医科大学生物化学与分子生物学教研室,辽宁沈阳110001

出　　处：《解剖科学进展》2013年第1期23-26,共4页Progress of Anatomical Sciences

摘　　要：目的探讨甲基硝基亚硝基胍(MNNG)对DNA造成损伤后,对人叉头蛋白转录因子(FOXO1)核质分布的影响。方法体外培养人肺腺癌细胞系H1299,经不同浓度MNNG处理细胞后,采用彗星电泳、细胞免疫荧光、Western blot等方法,对细胞DNA损伤程度、FOXO1核质定位情况及GADD45蛋白表达变化进行检测。结果 H1299细胞DNA损伤程度随MNNG处理浓度增加而显著增强,伴随DNA损伤程度的加深,FOXO1转录因子在核内的分布逐渐增加,且在细胞DNA发生损伤4h后GADD45表达升高。结论 MNNG能造成H1299细胞DNA损伤,并促进FOXO1转录因子的核转位,从而启动损伤修复过程。Objective To investgate the subcellular localization of human forkhead O1 transcription factor （FOXO1） responding to DNA damage induced by N-methyl-N＇-nitro-N-nitrosoguanidine（MNNG）. Methods H1299 cells were cultured and treated with various concentrations of MNNG in vitro. The DNA damage and subcellular localization of FOXO1 were determined by comet assay and immunofluorescence analysis respectively. The expression of GADD45 was quantified by western blot. Results More serious DNA damage was found as the increased concentrations of MNNG, and the expression level of FOXO1 also increased with the nuclear translocation in H1299 cells. And expression level of GADD45 started to increase at 4 hours after DNA damage was induced. Conclusion MNNG could cause DNA damage with dose dependent and promote nuclear translocation of FOXO 1 to activate DNA repair response.

关 键 词：FOXO1 DNA损伤 甲基硝基亚硝基胍 人肺癌 

分 类 号：R734.2[医药卫生—肿瘤] Q78[医药卫生—临床医学]