摘要
目的探讨基因启动子甲基化水平与全氟辛烷磺酸(PFOS)诱导的肝毒性早期过程相关性。方法在雌性SD大鼠受孕后2～21 d采用PFOS(0.1、0.6、2.0 mg/kg)灌胃染毒;在子鼠出生后21 d收集肝脏组织样本,用亚硫酸氢钠测序聚合酶链式反应法(BSP)结合质粒克隆后测序,检测烟酰胺腺嘌呤二核苷酸:醌氧化还原酶1(NQO1)和肉毒碱棕榈酰转移酶1A(CPT1A)基因启动子区域甲基化状态。结果与对照组(0%)比较,高剂量PFOS组子鼠肝脏NQO1基因甲基化状态有所上升,-573、-523、-507 3个位点分别升高了10%,而中低剂量组无变化(均为0%);CPT1A基因启动子区域甲基化状态无明显变化。结论出生前暴露于PFOS的子鼠肝脏中NQO1基因启动子甲基化水平升高。
Objective To examine the possibility of early epigenetic alteration in perfluorooctane sulphonate（PFOS）-exposed rat liver.Methods Pregnant Sprague-Dawley（SD） rats were exposed to PFOS at doses of 0.1,0.6,and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation day 2 to 21.The dams were allowed to give birth and liver samples from weaned（postnatal day 21） offspring rats were analyzed for individual genes such as NAD（P）H：quinone oxidoreductase（NQO1） and carnitine palmitoyltransferase 1A（CPT1A） promoter methylation level.Results In PFOS exposed weaned rats,compared to the control,methylation of critical CpG sites in NQO1 promoter was found up to 10% methylated in the livers of treated rats.Conclusion Early induced hypermethylation in critical cytosines within the NQO1 gene promoter region may be a significant biomarker of hepatic PFOS burden,though their direct role in PFOS induced-hepatotoxicity,including its potential carcinogenic action,needs further research.
出处
《中国公共卫生》
CAS
CSCD
北大核心
2012年第12期1597-1599,共3页
Chinese Journal of Public Health
基金
国家自然科学基金(21177046)
