四溴双酚A（TBBPA）对HepG2细胞的毒性机制及其剂量—反应关系研究
发布时间：2018-11-01 14:37
【摘要】：四溴双酚A(TBBPA)作为一种溴代阻燃剂被广泛应用于塑料、电子产品、建筑材料和纺织品中,目前在土壤、水体沉积物和大气等环境介质,以及水生生物、野生动物和人体血液、母乳样品中都有检出。目前有关TBBPA毒性研究的报道逐渐增多,对其肝肾毒性、免疫毒性、神经毒性和内分泌干扰效应等有了初步认识,但有关其细胞毒性及其作用机制尚不完全清楚。 本研究通过HepG2细胞模型,研究TBBPA暴露后的细胞毒性和毒作用机制,结果表明：TBBPA可影响HepG2细胞形态；HepG2细胞存活率与TBBPA处理呈浓度-效应关系和时间-效应关系,其12、24和48h的IC50分别为33.82、27.36和17.73μM；12、24和48h TBBPA处理的HepG2细胞LDH漏出率与TBBPA有浓度-效应关系；TBBPA处理导致HepG2细胞内ROS过量生成、GSH含量和SOD活力下降；加入抗氧化剂Trolox共同作用后,与TBBPA单独处理相比,HepG2细胞内ROS生成下降、GSH含量和SOD活力升高；在高剂量(30μM) TBBPA中加入抗氧化剂Trolox共同作用后,与TBBPA(30μM)单独处理相比,HepG2细胞存活率显著上升；20和30μMTBBPA处理均导致HepG2细胞线粒体膜电位下降和细胞凋亡率增加,但加入抗氧化剂Trolox共同作用后,其细胞凋亡情况无显著性改变。 另外,本研究采用BMD法,选择TBBPA染毒24h对HepG2细胞的抑制率为健康效应靶点,利用U.S.EPA开发的BMDS2.2软件,对其剂量-反应关系进行评估,结果表明其NOAEL、LOAEL、BMDL10和BMD10分别为10、15、9.45和10.34μM。 综合本研究结果,可得出如下结论：(1) TBBPA暴露可导致HepG2细胞死亡：(2) TBBPA能诱导HepG2细胞产生氧化应激；(3) TBBPA对HepG2细胞的毒性作用可能是通过氧化应激产生的；(4) TBBPA能诱导HepG2细胞凋亡;(5) TBBPA染毒24h对HepG2细胞抑制率影响的BMDL10为9.45μM。
[Abstract]:Tetrabromobisphenol A (TBBPA) is widely used as a brominated flame retardant in plastics, electronics, building materials and textiles, and in environmental media such as soil, water, sediment and atmosphere, as well as aquatic organisms. Wild animals and human blood, breast milk samples have been detected. At present, there are more and more reports about the toxicity of TBBPA, and it has a preliminary understanding of its liver and kidney toxicity, immune toxicity, neurotoxicity and endocrine disrupting effect, but the cytotoxicity and its mechanism are not completely clear. In this study, HepG2 cell model was used to study the mechanism of cytotoxicity and toxicity after TBBPA exposure. The results showed that TBBPA could affect the morphology of HepG2 cells. There was a concentration-effect relationship between the survival rate of HepG2 cells and TBBPA treatment, and the LDH leakage rate of HepG2 cells treated with 1224 and 48h IC50 was 33.82 渭 M ~ 27.36 and 17.73 渭 M ~ (12) O ~ (24) and 48 h TBBPA, respectively. There was a concentration-effect relationship between LDH leakage rate and TBBPA. TBBPA treatment resulted in the excessive production of ROS, the decrease of GSH content and SOD activity in HepG2 cells, the decrease of ROS production and the increase of GSH content and SOD activity in HepG2 cells compared with TBBPA alone. Compared with TBBPA (30 渭 M) alone, the survival rate of HepG2 cells increased significantly after the addition of antioxidant Trolox in high dose (30 渭 M) TBBPA). Both 20 and 30 渭 MTBBPA treatment led to the decrease of mitochondrial membrane potential and the increase of apoptosis rate of HepG2 cells, but the apoptosis of HepG2 cells did not change after the addition of antioxidant Trolox. In addition, the BMD method was used to evaluate the dose-response relationship of HepG2 cells induced by TBBPA for 24 hours by using BMDS2.2 software developed by U.S.EPA. The results showed that the inhibition rate of HepG2 cells exposed to TBBPA for 24 hours was the target of health effect. BMDL10 and BMD10 were 100.159.45 and 10.34 渭 M. Based on the results of this study, the following conclusions can be drawn: (1) TBBPA exposure can lead to the death of HepG2 cells; (2) TBBPA can induce oxidative stress in HepG2 cells; (3) the toxic effect of TBBPA on HepG2 cells may be caused by oxidative stress; (4) TBBPA could induce apoptosis of HepG2 cells, (5) the inhibitory rate of HepG2 cells induced by TBBPA for 24 h was 9.45 渭 m.
【学位授予单位】：中国环境科学研究院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R114
[Abstract]:Tetrabromobisphenol A (TBBPA) is widely used as a brominated flame retardant in plastics, electronics, building materials and textiles, and in environmental media such as soil, water, sediment and atmosphere, as well as aquatic organisms. Wild animals and human blood, breast milk samples have been detected. At present, there are more and more reports about the toxicity of TBBPA, and it has a preliminary understanding of its liver and kidney toxicity, immune toxicity, neurotoxicity and endocrine disrupting effect, but the cytotoxicity and its mechanism are not completely clear. In this study, HepG2 cell model was used to study the mechanism of cytotoxicity and toxicity after TBBPA exposure. The results showed that TBBPA could affect the morphology of HepG2 cells. There was a concentration-effect relationship between the survival rate of HepG2 cells and TBBPA treatment, and the LDH leakage rate of HepG2 cells treated with 1224 and 48h IC50 was 33.82 渭 M ~ 27.36 and 17.73 渭 M ~ (12) O ~ (24) and 48 h TBBPA, respectively. There was a concentration-effect relationship between LDH leakage rate and TBBPA. TBBPA treatment resulted in the excessive production of ROS, the decrease of GSH content and SOD activity in HepG2 cells, the decrease of ROS production and the increase of GSH content and SOD activity in HepG2 cells compared with TBBPA alone. Compared with TBBPA (30 渭 M) alone, the survival rate of HepG2 cells increased significantly after the addition of antioxidant Trolox in high dose (30 渭 M) TBBPA). Both 20 and 30 渭 MTBBPA treatment led to the decrease of mitochondrial membrane potential and the increase of apoptosis rate of HepG2 cells, but the apoptosis of HepG2 cells did not change after the addition of antioxidant Trolox. In addition, the BMD method was used to evaluate the dose-response relationship of HepG2 cells induced by TBBPA for 24 hours by using BMDS2.2 software developed by U.S.EPA. The results showed that the inhibition rate of HepG2 cells exposed to TBBPA for 24 hours was the target of health effect. BMDL10 and BMD10 were 100.159.45 and 10.34 渭 M. Based on the results of this study, the following conclusions can be drawn: (1) TBBPA exposure can lead to the death of HepG2 cells; (2) TBBPA can induce oxidative stress in HepG2 cells; (3) the toxic effect of TBBPA on HepG2 cells may be caused by oxidative stress; (4) TBBPA could induce apoptosis of HepG2 cells, (5) the inhibitory rate of HepG2 cells induced by TBBPA for 24 h was 9.45 渭 m.
【学位授予单位】：中国环境科学研究院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R114
【参考文献】
相关期刊论文 前10条
1 彭浩;金军;王英;刘伟志;杨若明;;液相色谱-电喷雾离子阱质谱分析土壤中四溴双酚-A[J];分析化学;2007年04期
2 陈玛丽;瞿t熺，
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