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BDE-99 同系物诱导人肝癌细胞系 HepG2 通过细胞凋亡死亡。

BDE-99 congener induces cell death by apoptosis of human hepatoblastoma cell line - HepG2.

机构信息

Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Departamento de Química, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP:14040-901, Bairro Monte Alegre, Ribeirão Preto, São Paulo, Brazil.

出版信息

Toxicol In Vitro. 2013 Mar;27(2):580-7. doi: 10.1016/j.tiv.2012.09.022. Epub 2012 Nov 2.

Abstract

Polybrominated Diphenyl Ethers (PBDEs) are an important class of flame retardants with a wide range of toxic effects on biotic and abiotic systems. The toxic mechanisms of PBDEs are still not completely understood because there are several different congeners with different chemical and biological characteristics. BDE-99 is one of these, widely found in the environment and biological samples, showing evidence of neurotoxic and endocrine disruption activities, but with little information about its action mechanism described in the current literature. This work investigated the effects of BDE-99 on the HepG2 cell line in order to clarify its toxic mechanism, using concentrations of 0.5-25 μM (24 and 48 h). Our results showed that BDE-99 could cause cell death in the higher concentrations, its activity being related to a decrease in mitochondrial membrane potential and an accumulation of ROS. It was also shown that BDE-99 induced the exposure of phosphatidylserine, caspases 3 and 9 activation and DNA fragmentation in HepG2 cells, without causing the release of LDH. Thus it was shown that BDE-99 could cause HepG2 cell death by apoptosis, suggesting its toxicity to the human liver.

摘要

多溴联苯醚(PBDEs)是一类重要的阻燃剂,对生物和非生物系统具有广泛的毒性作用。PBDEs 的毒性机制尚不完全清楚,因为有几种不同的同系物具有不同的化学和生物学特性。BDE-99 就是其中之一,广泛存在于环境和生物样本中,表现出神经毒性和内分泌干扰活性的证据,但关于其作用机制的信息在当前文献中描述甚少。本研究使用浓度为 0.5-25 μM(24 和 48 h)的 BDE-99 处理 HepG2 细胞系,以阐明其毒性机制。我们的结果表明,BDE-99 可在较高浓度下引起细胞死亡,其活性与线粒体膜电位降低和 ROS 积累有关。还表明 BDE-99 诱导 HepG2 细胞中磷脂酰丝氨酸暴露、caspase-3 和 caspase-9 的激活以及 DNA 片段化,而不会导致 LDH 释放。因此,BDE-99 可通过细胞凋亡导致 HepG2 细胞死亡,提示其对人肝的毒性。

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