四溴双酚A对人体正常肝细胞毒性效应及作用机制
Toxic Effects and Mechanism of Tetrabromobisphenol A on Human Normal Liver Cells L02
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摘要: 四溴双酚A（TBBPA）作为目前用量最大的一种溴系阻燃剂，在含TBBPA用品的生产、使用和废弃处置过程中，能够通过多种途径进入环境介质，造成持久性污染，危害生态系统和人体健康。为探明TBBPA对人体健康的潜在毒性效应及作用机制，选取人体正常肝细胞L02作为模型，通过分析暴露后细胞形态、存活率、胞内活性氧（ROS）含量、DNA损伤及细胞凋亡等变化。结果表明，TBBPA暴露导致L02细胞形态发生明显改变、存活率显著降低，细胞彗星实验拖尾现象明显增强；随着暴露浓度的升高，L02细胞胞内ROS含量、丙二醛（MDA）含量和氧化型谷胱甘肽/还原型谷胱甘肽（GSSG/GSH）比值均呈现剂量依赖性增加。40 μmol·L-1暴露条件下胞内ROS含量升高3.1倍；20 μmol·L-1和40 μmol·L-1暴露条件下，细胞凋亡率分别增加了3.2倍和4.8倍。推测TBBPA暴露对L02细胞的毒性效应作用机制为，暴露引起细胞氧化应激水平升高，ROS升高再引起DNA损伤程度增强，最终导致细胞凋亡率增加。上述研究结果将为评估TBBPA的毒性效应和健康风险提供科学依据。Abstract: Tetrabromobisphenol A (TBBPA) has become one of the most widely used brominated flame retardants. During the production, application and waste disposal of materials containing TBBPA, TBBPA can enter the environment through several ways, and result in the persistent organic pollution, which is harmful to the ecosystem and human health. In order to explore the potentially toxic effects of TBBPA on human health, L02 selected as model cells were exposed to TBBPA, and their morphology, survival rate, intracellular reactive oxygen species (ROS) content, DNA damage and apoptosis levels were detected. The results showed that the cellular morphology was changed, the survival rate was reduced significantly by TBBPA at the exposed concentration more than 10 μmol·L-1. And the trailing phenomenon of cell comet experiment was significantly enhanced. The intracellular ROS content, malondialdehyde (MDA) content and the ratio of oxidized/reduced glutathione (GSSG/GSH) increased with the concentration of TBBPA in well dose-dependent manner. The intracellular ROS content, MDA content and GSSG/GSH ratio increased by 3.1, 3.3 and 7.5 times, respectively, at the exposed concentration of 40 μmol·L-1. The apoptosis rate increased by 3.2 and 4.8 times at the exposed concentration of 20 μmol·L-1 and 40 μmol·L-1, respectively. It is speculated that the increase of TBBPA concentration induce the increase of ROS level which enhanced the DNA damage and eventually leaded to the increase of apoptosis rate. The results presented in this study will provide basic data for evaluating the toxic effects and health risk of TBBPA.
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Key words:
- TBBPA /
- human normal hepatocytes /
- oxidative stress /
- apoptosis
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