Zhang Zhijie, Zhao Xinyu, Qin Xiaosong
Clinical Laboratory, Shengjing Hospital, China Medical University, Shenyang 110011, China.
Complex Laboratory, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
Oncotarget. 2017 Jul 4;8(47):82185-82195. doi: 10.18632/oncotarget.18988. eCollection 2017 Oct 10.
Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.
农药残留引发的癌症相关健康问题近来愈发受到人们关注。甲氨基阿维菌素苯甲酸盐(EMB)因其作用靶点的特异性已在全球农业中广泛使用。尽管EMB对人类肝脏毒性的潜在风险及分子机制尚未得到充分表征。与中枢神经系统毒性的大量报道不同,EMB在人类肝细胞中的潜在遗传毒性和细胞毒性被忽视且研究非常有限。在本研究中,我们确定了EMB对人类正常肝细胞(QSG7701细胞系)的遗传毒性和细胞毒性。我们证明EMB抑制了QSG7701细胞的活力并诱导了DNA损伤。通过已建立的细胞毒性检测方法来表征EMB对QSG7701细胞毒性的机制。典型的染色质浓缩和DNA片段化表明EMB诱导了QSG7701细胞凋亡。细胞内生化结果表明,EMB增强QSG7701细胞凋亡的同时伴有活性氧生成、线粒体膜电位丧失、细胞色素c释放、上调Bax/Bcl-2比值以及激活caspase-9/-3。我们关于EMB诱导QSG7701细胞死亡可能通过线粒体介导的内源性凋亡途径的结果,将有助于提高人们对EMB这种广泛使用的农药对人类影响的认识,并揭示潜在遗传毒性的潜在机制。