Key Laboratory of Ministry of Education on Pollution Control and Ecosystem Restoration in Industry Clusters, Guangdong Provincial Engineering and Technology Research Center for Environmental Risk Prevention and Emergency Disposal, School of Environment and Energy, South China University of Technology, Guangzhou, 510006, Guangdong, China.
Key Laboratory of Ministry of Education on Pollution Control and Ecosystem Restoration in Industry Clusters, Guangdong Provincial Engineering and Technology Research Center for Environmental Risk Prevention and Emergency Disposal, School of Environment and Energy, South China University of Technology, Guangzhou, 510006, Guangdong, China.
Chemosphere. 2019 Apr;221:693-702. doi: 10.1016/j.chemosphere.2019.01.074. Epub 2019 Jan 16.
Organophosphate flame retardants (OPFRs) and brominated flame retardants (BFRs) are frequently detected in indoor environment at high levels, posing health risks to humans. However, the potential cytotoxicity mediated by OPFRs and BFRs in relevant human cell models is limited. In current study, non-small cell lung cancer A549 cell was employed to investigate toxicity mechanisms of typical OPFRs (i.e., tris (2-chloroethyl) phosphate (TCEP), tris-(2-chloropropyl) phosphate (TCPP), tricresy phosphate (TCP), triphenyl phosphate (TPHP) and BFRs (i.e., 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 3,3', 5,5'-tetrabromobisphenol A (TBBPA)). It was found that BDE-47 exhibited the strongest cytotoxicity, followed by TBBPA, TPHP, TCP, TCPP and TCEP. OPFRs and BFRs could cause the reduction of cell viability of A549 cell in both dose- and time-dependent manner after exposure for 24 and 48 h. Simultaneously, excessive generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, cell apoptosis and overload of intracellular free Ca demonstrated that cytotoxicity induced by OPFRs and BFRs were mediated by oxidative stress. Of note, the survival rate of cell significantly increased when pretreated with Ac-DEVD-CHO, suggesting that caspase-3 dependent mitochondrial pathway may have played a primary role in the process of A549 cell apoptosis.
有机磷阻燃剂 (OPFRs) 和溴化阻燃剂 (BFRs) 经常在室内环境中高水平检出，对人类健康构成威胁。然而，相关人体细胞模型中 OPFRs 和 BFRs 介导的潜在细胞毒性有限。在本研究中，非小细胞肺癌 A549 细胞被用于研究典型 OPFRs（即三 (2-氯乙基) 磷酸酯 (TCEP)、三 (2-氯丙基) 磷酸酯 (TCPP)、磷酸三乙酯 (TCP)、磷酸三苯酯 (TPHP)）和 BFRs（即 2,2',4,4'-四溴二苯醚 (BDE-47)、3,3',5,5'-四溴双酚 A (TBBPA)）的毒性机制。结果发现，BDE-47 的细胞毒性最强，其次是 TBBPA、TPHP、TCP、TCPP 和 TCEP。OPFRs 和 BFRs 暴露 24 和 48 小时后，以剂量和时间依赖的方式导致 A549 细胞活力降低。同时，过量的活性氧 (ROS) 生成、线粒体膜电位 (MMP) 功能障碍、细胞凋亡和细胞内游离 Ca 过载表明，OPFRs 和 BFRs 引起的细胞毒性是通过氧化应激介导的。值得注意的是，用 Ac-DEVD-CHO 预处理后，细胞存活率显著增加，这表明 caspase-3 依赖的线粒体途径可能在 A549 细胞凋亡过程中发挥了主要作用。
