小鼠氚水内污染诱导的DNA甲基化改变
郑璐琳1，黄铖铖1，孙秀锦1，包广粮2，孙亮1，陈秋1，崔凤梅1
基金项目：基金项目：国家自然科学基金（30800922，81172706） 作者简介：郑璐琳(1987年出生), 女, 在读研究生, 放射毒理学方向 通信联系人：崔凤梅(1975年出生), 女, 副教授, 放射毒理学方向.

（1. 苏州大学医学部放射医学与防护学院,苏州 215123； 2. 中国科学院上海应用物理研究所,上海 201800）
摘要：本文建立氚水染毒小鼠模型，采用甲基化DNA免疫沉淀-芯片(MeDIP-chip)杂交技术分析小鼠肝组织基因启动子CpG甲基化情况，并检测了肺、肝、肾脏组织DNMT1的表达水平。结果显示，不同浓度氚染毒10 d的小鼠肝脏组织基因组出现了新的甲基化位点，而且高浓度和低浓度染毒组的共同发生甲基化的基因有19个，17个发生在启动子的CpG。随着氚水10 初始注入量增加，累积剂量增大，肺、肝、肾组织DNMTl表达量相应降低。氚水初始注入量为5.55×105 Bq/g时，随注入后时间延长，累积剂量增大，DNMTl表达量下降后再恢复。实验结果提示，甲基化改变的差异基因可能在氚水内照射损伤时起调控作用，不同组织中DNMT1的检测可用于辐射损伤的早期检测或损伤恢复的评估。

关键词：DNA甲基化；氚；DNMT1
中图分类号：R818.03
The change of DNA methylation induced by HTO internal exposure in mice
Zheng Lulin1, Huang Chengcheng1, Sun Xiujing1, Bao Guangliang2, Sun Liang1, Chen Qiu1, Cui Fengmei1
(1. School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou 215123; 2. Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 200000)

Abstract: We established a mouse model of internal radiation of triated water(HTO). The methylation levels of promoter CpG were assessed by immunoprecipitation-chip (MeDIP-chip) hybridization of DNA methylation and the expression of DNA methyltransferase（DNMT1）were detected in different organs. The results showed some genes were getting methylated in mouse liver tissue 10 days after injection with different concentration of HTO, and there were the 30 same 19 genes getting methylated in both high and low concentration groups, 17 of them were at promotor CpG. With the increase concentration of HTO, the expression level of DNMT1 decreased in lung, liver and renal tissues. And when the concentration was 5.55×105 Bq/g, as time moved on, cumulative dose increased, the expression level of DNMT1 decreased and then went up. These results indicated those genes getting methylated probably be involved in regulating the 35 process of radiation damage caused by HTO, and DNMT1 expression level in different organs could be used for early detection of radiation damage or evaluation of damage repairing.