【摘要】 十溴联苯醚(BDE-209)是使用最多的一种多溴阻燃剂,由于具有高亲脂性和低挥发性,容易蓄积在生物体内,在人体血清、母乳、肝脏等组织中均有检出;其环境脱溴产物九溴一氯联苯醚(Cl-BDE-208)也在血清样品和环境样品中被频频检出,而目前对这种化合物的毒理学研究,特别是对人体早期健康效应的研究较少。为了评估Cl-BDE-208和BDE-209的早期健康效应,以人乳腺癌细胞MCF-7为模型,环境相关浓度(0.375~3μmol·L-1)为暴露浓度,检测Cl-BDE-208和BDE-209对重复序列LINE-1、全基因组DNA甲基化(GDM)和雌激素受体基因(包括ESR1和ESR2)甲基化水平的改变。结果表明,Cl-BDE-208和BDE-209都可能通过降低DNA甲基化转移酶(DNMTs)活性而诱导了LINE-1和GDM的低甲基化,8-羟基脱氧鸟苷(8-OHd G)水平的升高可能参与了BDE-209引起的低甲基化过程;同时通过促进雌激素受体α(ESR1)基因的高甲基化而显著下调了ESR1基因的表达,而对雌激素受体β(ESR2)基因甲基化水平并没有显著影响。Cl-BDE-208和BDE-209都可能通过改变DNA甲基化水平而影响人体的早期健康效应,同时ESR1基因的高甲基化可能是Cl-BDE-208和BDE-209引起内分泌毒性的机制之一。更多还原

【Abstract】 Decabromodiphenyl ether(BDE-209) is the mostly used compound of polybrominated flame retardants.The high lipid solubility and low vapor pressure contribute to their bioaccumulation. BDE-209 has been detected in human blood, milk, and liver tissues. Monochloro-nonabromo diphenyl ethers(Cl-BDE-208), the environmental metabolite of BDE-209 is also found in human tissues, but the information of Cl-BDE-208 and BDE-209 toxicity is limit-ed. The objective of this study is to investigate whether environmental relative concentrations BDE-209 and Cl-BDE-208(0.375 ~ 3 μmol·L-1) could cause DNA methylation changes of several DNA methylation biomarkers in MCF-7cells, including repetitive elements(LINE-1), global DNA methylation(GDM) and estrogen receptor gene(ESR1 and ESR2), and to explore the possible mechanism. Results showed that Cl-BDE-208 and BDE-209 down-regulated LINE-1 and global DNA methylation through DNMTs activity decrease, and 8-OHd G level increase may be involved in BDE-209-induced hypomethylation. More interesting, Cl-BDE-208 and BDE-209 inhibited ESR1 gene expression by promoting the DNA methylation in promoter area, while both compounds have no effects on ESR2 gene. Results suggested that Cl-BDE-208 and BDE-209 have the adverse health outcomes, and ESR1 gene hypermethylation may be the potential mechanism of endocrine toxicity of BDE-209.更多还原