青年科学工作者论坛2008年第5期

于洲 严卫星 张连峰^[1]  徐海滨²

中国疾病预防控制中心营养与食品安全所，北京 100021

 

摘要：目的 依据胚胎干细胞所具有向心肌细胞分化的能力，建立体外分化发育毒性评价的模型，并对其判定受试物发育毒性强弱的有效性进行验证，拓展体外发育毒性安全性评价技术手段。方法 利用悬滴、悬浮培养方法，通过不同浓度青霉素G、苯妥英钠和氟尿嘧啶作用，检测胚胎干细胞分化为心肌细胞的能力，结合MTT法获得的受试物细胞毒性结果，判断受试物的发育毒性。结果 青霉素G、苯妥英钠和氟尿嘧啶的ID₅₀（D3）分别为1099μg/ml、47.4μg/ml和0.023μg/ml，其发育毒性的判定依次无、弱和强。结论 建立的胚胎干细胞实验模型能够判定氟尿嘧啶、苯妥英钠、和青霉素G发育毒性，结果与ECVAM的结论一致，可用于发育毒性的筛选和评价。

关键词：胚胎干细胞  发育毒性

中图分类号：Q132.7                   文献标识码：A

YU Zhou,YAN Weixing,ZHANG Lianfen,XU Haibin

Institute of Nutrition and Food Safety, China CDC, Beijing 100021, China

Abstract: Objective According trend of differentiation cardiomyocyte of embeyonic stem cell ,the model of EST has been built and the validation of the model is needed to be tested. It is profit to improve the method of safety evaluation.Methods  The embryonic stem cell differentiates into cardiomyocyte in different concentrations of PenicillinG,DPH and 5-FU with hanging and suspending culture conditions.With the results of cytotoxicity ,the different embryonictoxicity characteristics of different substants may be detected clearly. Results  The ID₅₀（D3） concentration of three embryotoxicants were 1099μg/ml,47.4μg/ml and 0.023μg/ml. PenicillinG,DPH and 5-FU were discriminated as none-embryotoxicity, weak-embryotoxicity and strong-embryotoxicity. Conclusion Test compounds betweem three classes were discriminated correctly .The validation of EST model that established by us is high.

Key words: embryonic stem cells, developmental toxicity, validation

 

 

 

 

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