于洲 嚴衛星 張連峰^[1]  徐海濱²

中國疾病預防控制中心營(yíng)養與食品安全所，北京 100021

 

摘要：目的 依據胚胎干細胞所具有向心肌細胞分化的能力，建立體外分化發(fā)育毒性評價(jià)的模型，并對其判定受試物發(fā)育毒性強弱的有效性進(jìn)行驗證，拓展體外發(fā)育毒性安全性評價(jià)技術(shù)手段。方法 利用懸滴、懸浮培養方法，通過(guò)不同濃度青霉素G、苯妥英鈉和氟尿嘧啶作用，檢測胚胎干細胞分化為心肌細胞的能力，結合MTT法獲得的受試物細胞毒性結果，判斷受試物的發(fā)育毒性。結果 青霉素G、苯妥英鈉和氟尿嘧啶的ID₅₀（D3）分別為1099μg/ml、47.4μg/ml和0.023μg/ml，其發(fā)育毒性的判定依次無(wú)、弱和強。結論 建立的胚胎干細胞實(shí)驗模型能夠判定氟尿嘧啶、苯妥英鈉、和青霉素G發(fā)育毒性，結果與ECVAM的結論一致，可用于發(fā)育毒性的篩選和評價(jià)。

關(guān)鍵詞：胚胎干細胞  發(fā)育毒性

中圖分類(lèi)號：Q132.7                   文獻標識碼：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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