4种新污染物对5种不同细胞的联合毒性研究
Joint Toxicity of Four Emerging Pollutants on Five Different Types of Cells
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摘要: 随着人类社会的发展，新污染物的种类逐渐增多。目前新污染物的毒性研究主要集中于单一毒性的评价，由于人类可能通过各种途径暴露于新污染物的混合物，因此评估新污染物混合物对人类健康的潜在风险越来越受到关注。本研究采用5种常见的体外毒性研究细胞模型——人正常肝细胞L02、小鼠正常肝细胞AML12、人肾小管上皮细胞HK2、大鼠胶质瘤细胞C6、小鼠海马神经元细胞HT22，测定不同浓度炔雌醇(ethinyl estradiol, EE2)、双酚A(bisphenol A, BPA)、邻苯二甲酸二丁酯(dibutyl phthalate, DBP)、全氟辛酸(perfluorooctanoic acid, PFOA)对5种细胞的相对生长抑制率，分别计算污染物在不同生长抑制率下的效应浓度(F%-maximum effective concentration, ECF，其中F=10、20、25、33、50)。按照EC50∶EC50 (半数效应浓度)、EC33∶EC33∶EC33 (生长抑制率为33%下的效应浓度)、EC25∶EC25∶EC25∶EC25 (生长抑制率为25%下的效应浓度)的比例分别进行二元、三元、四元等毒性比例混合，以1/2为稀释因子进行浓度梯度处理，计算抑制率并拟合实际作用曲线，采用浓度加和(concentration addition, CA)模型和独立作用(independent action, IA)模型预测不同污染物之间的联合效应。4种污染物对5种细胞的生长抑制均存在剂量-效应关系。暴露48 h后，在所有细胞中EE2的毒性最大，PFOA的毒性最小，HK2细胞对4种污染物的敏感性最弱。在二元组合中，EE2与BPA的混合物在2种神经细胞C6与HT22上都存在明显的协同作用。随着混合物的组分增加，三元和四元混合物更易产生相加与拮抗作用。4种污染物对所有的受试细胞都具有一定的毒性，其联合效应会随着组分及浓度等的变化而不同。Abstract: The development of society has led to an increase in the types of new pollutants. With the development of society, the types of new pollutants are gradually increasing. Currently, the toxicity studies on new pollutants mainly focuses on the evaluation of a single toxicity. However, as humans may be exposed to mixtures of new pollutants through various routes, the assessment of the potential risks of these mixtures to human health has received increasing attention. This study used L02, AML12, HK2, C6, and HT22 cells as models to measure the growth inhibition rates of five types of cells under different concentrations of ethinyl estradiol (EE2), bisphenol A (BPA), dibutyl phthalate (DBP), and perfluorooctanoic acid (PFOA). The effective concentrations (ECF, where F = 10, 20, 25, 33, 50) of emerging pollutants at different growth inhibition rates were calculated. Binary, ternary, and quaternary mixtures of emerging pollutants were designed according to the ratios of EC50∶EC50, EC33∶EC33∶EC33, and EC25∶EC25∶EC25∶EC25, and then diluted with a dilution ratio of 1/2. The inhibition rates were calculated, and the actual action curves were fitted. The concentration addition model (CA) and the independent action model (IA) were used to evaluate the combined effects of the different emerging pollutants. There was a dose-effect relationship between the four kinds types of emerging pollutants on the growth inhibition of the 5 types of cells. After 48 hours of exposure, EE2 showed the highest toxicity, while PFOA showed the least toxicity in all types of cells. HK2 showed the weakest sensitivity to the four types of emerging pollutants. In binary combinations, EE2+BPA showed significant synergistic inhibition on C6 and HT22. As the number of components increased, ternary and quaternary mixtures were more likely to exhibit additive and antagonistic effects. The four types of emerging pollutants were toxic to all tested cells, and the combined toxic effects varied with the changes in components and concentrations.
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