基于Cell Painting细胞表型分析方法评价邻苯二甲酸二环己酯的毒性效应  

Evaluate the toxicity of dicyclohexyl phthalate using the phenotype analysis method of Cell Painting

作　　者：施嘉琛[1] 丰一兴[1] 李明[1] 郑朝慧 张晶[1] 邵兵[1] SHI Jia-chen;FENG Yi-xing;LI Ming;ZHENC Chao-hui;ZHANG Jing;SHAO Bing(Beijing Center for Disease Prevention and Control,Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning,Beijing 100013,China;Chinese Center for Disease Control and Prevention,National Institute for Radiological Protection,Beijing 100088,China)

机构地区：[1]北京市疾病预防控制中心食物中毒诊断溯源技术北京市重点实验室,北京100013 [2]中国疾病预防控制中心辐射防护与核安全医学所,北京100088

出　　处：《毒理学杂志》2024年第5期338-343,共6页Journal of Toxicology

基　　金：高层次公共卫生技术人才培养计划(学科骨干-01-033)。

摘　　要：目的 利用高通量细胞表型分析Cell Painting方法,开展塑化剂邻苯二甲酸二环己酯(DCHP)雌激素效应和心肌毒性机制研究。方法 基于Cell Painting的细胞高通量筛选方法,获得DCHP对人骨肉瘤细胞U2OS多个亚细胞结构改变的数据,与公开发布的细胞图谱数据库中具有雌激素效应和心肌毒性效应参照物的数据进行比较,通过图像参数计算来研判DCHP在这两方面毒性效应的作用机制。结果 DCHP的雌激素效应可能与盐皮质激素受体拮抗剂作用机制相似;DCHP的心肌细胞毒性可能与心肌肌球蛋白激活剂和肾上腺素受体激动剂作用机制相似。结论Cell Painting作为一种基于高通量细胞表型分析的生物作用机制的研究方法,可以为目标化学品的作用机制提供评价筛选的依据,有助于提升目标化学品毒理学机制的评价效率。Objective To investigate the mechanism of estrogen effect and myocardial toxicity of plasticizer dicyclohexyl phthalate(DCHP)using Cell Painting,a high-throughput cell phenotype analysis method.Methods Based on the cell high-throughput screening method of Cell Painting,data on the structural changes of multiple subcellular cells in human osteosarcoma U2OS induced by DCHP were obtained.The data were compared with the data of substances with estrogen effect and myocardial toxicity in the published cell atlas database,and the mechanisms of DCHP's toxic effects in these two aspects were evaluated through scoring.Results The result showed that the estrogen effect of DCHP may be similar to the mechanism of action of mineralocorticoid receptor antagonists;The myocardial cytotoxicity of DCHP may be similar to the mechanisms of action of cardiac myosin activators and adrenergic receptor agonists.Conclusion Cell Painting,as a biological mechanism of action based on high-throughput cell phenotype analysis,can provide a basis for evaluating the mechanism of action of target compounds and help improve the efficiency of conducting research on the toxicological mechanisms of test chemicals.

关 键 词：高通量表型分析 Cell Painting 计算毒理学 邻苯二甲酸二环己酯 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]