多菌灵和苯醚甲环唑对SK-N-SH细胞的联合毒性效应  

Combined Toxic Effects of Carbendazim and Difenoconazole on SK-N-SH Cells

作　　者：张婉君 罗荪琳 范瑞祺 贾栗 苑晓燕 陈义强[1] Zhang Wanjun;Luo Sunlin;Fan Ruiqi;Jia Li;Yuan Xiaoyan;Chen Yiqiang(State Key Laboratory of Animal Nutrition,College of Animal Science and Technology,China Agricultural University,Beijing 100193,China;Center of Disease Control and Prevention,People’s Liberation Army,Beijing 100071,China)

机构地区：[1]动物营养学国家重点实验室,中国农业大学动物科技学院,北京100193 [2]中国人民解放军疾病预防控制中心,北京100071

出　　处：《生态毒理学报》2022年第5期373-382,共10页Asian Journal of Ecotoxicology

基　　金：食品安全关键技术研发专项(2018YFC1603002)。

摘　　要：生蔬中的农药残留会导致农药在人体内蓄积并产生危害,尤其是农药混合残留可能产生农药“鸡尾酒”效应,导致毒性效应叠加、增强或减弱。因此研究农药混合物的联合毒性效应及机制对食品安全风险评估具有重要意义。本研究以人神经瘤细胞母细胞(SK-N-SH细胞)为模型,以等毒性配比法设计联合细胞毒性实验,采用联合指数方法探讨多菌灵和苯醚甲环唑的联合细胞毒性。此外,采用析因设计探讨二者对SK-N-SH细胞内活性氧(reactive oxygen species,ROS)生成的联合作用。结果显示,在不同效应水平,多菌灵和苯醚甲环唑对SK-N-SH细胞活力表现出不同的联合作用模式。当混合物的效应水平为0~50%时,多菌灵和苯醚甲环唑的毒性效应表现为拮抗作用;混合物的效应水平为50%~100%时,多菌灵和苯醚甲环唑表现为协同作用。此外,当苯醚甲环唑浓度较低时(16.88μmol·L^(-1)),二者对ROS的生成表现为拮抗作用;当苯醚甲环唑浓度较高时(22.08μmol·L^(-1)),二者对ROS的生成表现为协同作用。结果提示多菌灵和苯醚甲环唑具有联合神经毒性,且ROS生成的氧化应激机制在这二者的联合神经毒性中发挥作用。此研究结果为农药复合暴露对人类健康的风险提供实验依据。Pesticide residues in fruits and vegetables can cause the accumulation of pesticides and harm to the human body.In particular,mixed pesticide residues may produce a pesticide cocktail effect,resulting in superimposition,enhancement or reduction of toxic effects.Therefore,studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to food safety risk assessment.In this study,human neuroma cell blasts(SK-N-SH cells)were used as a cell model.The combined cytotoxicity assay was designed under the condition of equal toxicity ratio.The combined cytotoxic effects of carbendazim and difenoconazole were evaluated by the combination index analysis.In addition,a factorial design was adopted to assess the combined effects of these two on the production of reactive oxygen species(ROS)in SK-N-SH cells.The results showed that carbendazim and difenoconazole exerted different combined effect modes on SK-N-SH cell viability at different effect level.When the effect level of the mixture was 0~50%,carbendazim and difenoconazole exerted antagonistic effects on SK-N-SH cell viability;when the effect level of the mixture was 50%~100%,the two showed synergistic effects on SK-N-SH cell viability.In addition,when the difenoconazole concentration was low(16.88μmol·L^(-1)),the two exerted antagonistic effects on the generation of ROS;when the difenoconazole concentration was high(22.08μmol·L^(-1)),the two had antagonistic effects on ROS generation.These results suggest that carbendazim and difenoconazole yield combined neurotoxicity,and the oxidative stress mechanism of ROS generation plays a role in the combined neurotoxicity of the two.The findings in this study provide experimental evidence for the risk of pesticide compound exposure to human health.

关 键 词：农药 多菌灵 苯醚甲环唑 细胞毒性 联合作用 

分 类 号：X171.5[环境科学与工程—环境科学]