PDF(Pubmed)
Abstract：
Tetrabromobisphenol A (TBBPA) is a flame retardant that adversely affects the environment and human health. The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene regulation, mainly related to pathways associated with the endocrine system. The quantitative polymerase chain reaction (qPCR) confirmed that prolonged exposure gradually activated the thyroid hormone and parathyroid hormone signaling pathways. The expression levels of genes related to the thyroid hormone signaling pathway were upregulated (1.15-8.54 times) after five generations of exposure to 1 and 81 nM TBBPA. Furthermore, co-exposure to 81 nM TBBPA and 0.5 nM thyroid hormone receptor antagonist for five generations significantly reduced the expression of thyroid hormone and parathyroid hormone receptors. Meanwhile, 81 nM TBBPA inhibited the activation of the Ras pathway and downregulated Ras gene expression level (3.7 times), indicating the association between the toxic effect and thyroid hormone receptors. Additionally, our experiments revealed that the thyroid hormone pathway regulated the induction of the Ras signaling pathway by TBBPA. The study thus proves that daily exposure to TBBPA interferes with the thyroid hormone signaling pathway and subsequently the endocrine system.
摘要：
四溴双酚A（TBBPA）是一种对环境和人类健康产生不利影响的阻燃剂。本研究每天将HepG2细胞暴露于低浓度的TBBPA，以研究基因调控的变化。主要与内分泌系统相关的途径有关。定量聚合酶链反应（qPCR）证实，长时间暴露逐渐激活甲状腺激素和甲状旁腺激素信号通路。暴露于1和81nMTBBPA的五代后，与甲状腺激素信号通路相关的基因的表达水平上调（1.15-8.54倍）。此外，共暴露于81nMTBBPA和0.5nM甲状腺激素受体拮抗剂五代显著降低甲状腺激素和甲状旁腺激素受体的表达。同时,81nMTBBPA抑制Ras途径的激活并下调Ras基因表达水平（3.7倍），表明毒性作用与甲状腺激素受体之间的关联。此外,我们的实验表明，甲状腺激素通路调节TBBPA诱导的Ras信号通路。因此，该研究证明，每天暴露于TBBPA会干扰甲状腺激素信号通路，进而干扰内分泌系统。
