摘要
目的研究常用近交系品系C57BL/6J(B6)和129X1/SvJ(129)小鼠急性砷暴露后肝脏全基因组DNA甲基化的差异。方法将健康成年清洁级雄性野生型B6和129小鼠各18只按体重随机分别分为3组,分别为对照组(生理盐水,24 h),亚砷酸钠(5 mg/kg)染毒后6 h、24 h组,每组各6只。采用一次性灌胃方式进行染毒,采用ELISA法检测肝脏中全基因组DNA甲基化水平,采用Western blot法检测肝脏中DNA甲基转移酶DNMT1、DNMT3a、DNMT3b以及砷甲基化相关酶亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)、甲硫氨酸合成酶(methionine synthetase,MTR)、砷甲基转移酶(CYT19)蛋白的表达水平。结果与对照组相比,亚砷酸钠处理后6 h的129小鼠肝脏中全基因组DNA甲基化水平降低,亚砷酸钠处理后24 h的B6小鼠肝脏中全基因组DNA甲基化水平升高,差异均有统计学意义(P<0.05)。在基础水平下,129小鼠肝脏中全基因组DNA甲基化水平高于B6小鼠,差异有统计学意义(P<0.05);亚砷酸钠处理后24 h时,129小鼠肝脏中全基因组DNA甲基化水平低于B6小鼠,差异有统计学意义(P<0.05)。与对照组相比,亚砷酸钠染毒后24 h的B6小鼠肝脏中DNMT1、DNMT3a、DNMT3b的蛋白表达水平均较高,而亚砷酸钠染毒后6 h的129小鼠肝脏中DNMT1、DNMT3a的蛋白表达水平均较低,差异有统计学意义(P<0.05)。基础水平下的129小鼠肝脏中DNMT1、DNMT3a、DNMT3b的蛋白表达水平及亚砷酸钠染毒后24 h的129小鼠肝脏中DNMT3b的蛋白表达水平均高于B6小鼠,差异有统计学意义(P<0.05)。与对照组相比,仅亚砷酸钠染毒后24 h的B6小鼠肝脏中MTHFR、MTR的蛋白表达水平均较高,差异有统计学意义(P<0.05);而亚砷酸钠染毒129小鼠肝脏中MTHFR、MTR、CYT19的蛋白表达水平均无明显变化。基础水平下的129小鼠肝脏中MTHFR、MTR的蛋白表达水平及亚砷酸钠染毒后6 h的129小鼠肝脏中MTHFR的蛋白表达水平均高于B6小鼠,差异有统
Objective To analyze the differences in genome-wide DNA methylation in the liver between C57 BL/6 J(B6)and129 X1/SvJ(129)mice after acute arsenic exposure.Methods Healthy male B6 and 129 mice(weight:20-25 g)of clean grade aged 8 to 12 weeks were randomly divided into three groups by body weight,Veh(physiological saline,24 h),6 and 24 h5 mg/kg arsenic-treated groups(n=6).5 mg/kg sodium arsenite was administrated by gavage once.The level of genome-wide DNA methylation in the liver was measured by ELISA kit,the protein levels of DNMT1,DNMT3 a,DNMT3 b and arsenic-methylation-related enzymes MTHFR,MTR and CYT19 in the liver were detected by Western blot,6 and 24 h after exposure to sodium arsenite.Results Compared with the control group,the genome-wide DNA methylation level was significantly decreased in the liver of 129 mice 6 h after arsenite administration(P<0.05),and was significantly increased in the liver of B6 mice 24 h after arsenite administration(P<0.05).The genome-wide DNA methylation level in the liver of 129 mice of control group was significantly higher than that of B6 mice of control group(P<0.05);The genome-wide DNA methylation level in the liver of 129 mice was significantly lower than that of B6 mice 24 h after arsenite administration(P<0.05).Compared with the control group,protein levels of DNMT1,DNMT3 a and DNMT3 b were significantly increased in the liver of B6 mice 24 h after arsenite administration(P<0.05),but protein levels of DNMT1 and DNMT3 a were significantly decreased in the liver of 129 mice 6 h after arsenite administration(P<0.05).Protein levels of DNMT1,DNMT3 a and DNMT3 b of control group and the protein levels of DNMT3 b 24 h after arsenite administration in the liver of 129 mice were significantly higher than those of B6 mice(P<0.05).Compared with the control group,only protein levels of MTHFR and MTR were significantly increased in the liver of B6 mice 24 h after arsenite administration(P<0.05);Howere,protein levels of MTHFR,MTR and CYT19 were not significantly different in the liv
作者
周若楠
武瑞瑞
陈欣
徐晓航
陈诗敏
王惠惠
徐苑苑
ZHOU Ruo-nan;WU Rui-rui;CHEN Xin;XU Xiao-hang;CHEN Shi-min;WANG Hui-hui;XU Yuan-yuan(Laboratory of Chronic Diseases and Environmental Genomics,School of Public Health,China Medical University,Shenyang,Liaoning 110122,China)
出处
《环境与健康杂志》
CAS
北大核心
2019年第8期671-675,共5页
Journal of Environment and Health
基金
国家自然科学基金(81573187)
辽宁省“兴辽英才”项目(XLYC1807225).
