小剂量X射线对小鼠全基因组CpG岛甲基化水平的影响  

Genome-wide screening of CpG island methylation changes induced by low-dose X-ray radiation in mice

作　　者：王静子[1,2] 冒晓蓓[1,2] 张有为[1,2] 薛利军[1,2] 刘小北[1,2] 耿建[1,2] 任丽丽[1,2] 郁红菊[1,2] 陈龙邦[1,2] 褚晓源[1,2] 

机构地区：[1]南方医科大学南京临床学院 [2]南京军区南京总医院肿瘤内科,江苏南京210002

出　　处：《南方医科大学学报》2014年第2期228-231,共4页Journal of Southern Medical University

基　　金：南京军区医药卫生科研基金(11MA092)

摘　　要：目的探讨小剂量X射线(LDR)暴露对小鼠启动子CpG岛甲基化水平的影响。方法 BALB/c雄性小鼠20只按随机数字表法均分为2组:对照组和分次0.5 Gy(0.05 Gy/d×10 d)照射组。末次照射后2 h摘除眼球取血。采用Roche-NimbleGen小鼠甲基化DNA免疫共沉淀-芯片(MeDIP-chip),分析小鼠全血基因组启动子CpG岛甲基化改变,并利用MeDIP-qPCR(甲基化DNA免疫共沉淀—实时定量PCR)方法检测目的基因启动子区域DNA甲基化水平。结果与对照组相比较,分次照射组全血基因组共筛选出811个基因启动子区甲基化水平存在显著差异(P<0.05)。这些基因涉及几乎所有主要生物学过程。经MeDIP-qPCR验证,挑选出的8个基因(Rad23b、Tdg、Ccnd1、Ddit3、Llgl1、Rasl11a、Tbx2、Slc6a15)的甲基化水平与芯片结果一致。结论 LDR诱导特定基因的CpG岛发生高甲基化,可能参与LDR损伤的分子机制。Objective To study the methylation changes in promoter CpG islands induced by low-dose X-ray radiation （LDR）. Methods Twenty male BALB/c mice were randomly divided into control and fractionated radiation group exposed to 6 MV X-ray for 10 days （0.05 Gy/day）. All the mice were sacrificed 2 h after the last radiation on day 10, and blood samples were collected for detecting DNA methylation changes using Roche-NimbleGen mouse DNA methylation 3 ＆#215; 720K Promoter Plus CpG Island Array. MeDIP-qPCR was used to further validate the methylation status of specific genes. Results A total of 811 genes were found to show specific hypermethylation in fractional radiation group as compared with the control group, involving almost all the main biological processes by GO analysis. Eight candidate genes （Rad23b, Tdg, Ccnd1, Ddit3, Llgl1, Rasl11a, Tbx2, and Slc6a15） were confirmed to be hypermethylated in LDR samples by MeDIP-qPCR, consistent with the results of the methylation chip study. Conclusion LDR induces promoter hypermethylation on specific genes, which may contribute to radiation-induced pathogenesis.

关 键 词：低剂量辐射 甲基化 DNA免疫共沉淀-芯片 

分 类 号：R818[医药卫生—放射医学]