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使用基于ReProGlo干细胞的Wnt报告基因检测法预测胚胎毒性潜力。

Prediction of embryotoxic potential using the ReProGlo stem cell-based Wnt reporter assay.

作者信息

Uibel Frederik, Schwarz Michael

机构信息

Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Wilhelmstr. 56, 72074 Tübingen, Germany.

Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Wilhelmstr. 56, 72074 Tübingen, Germany.

出版信息

Reprod Toxicol. 2015 Aug 1;55:30-49. doi: 10.1016/j.reprotox.2014.09.009. Epub 2014 Sep 28.

Abstract

The ReProGlo assay was developed in 2009 to predict embryotoxic potential of drugs and chemicals by use of a stem cell-based in vitro system. It utilizes a luciferase reporter to detect drug-induced alterations in the canonical Wnt/β-catenin signaling pathway, which is involved in regulation of early embryonic development. It allows the simultaneous determination of cell viability and luciferase reporter activity in a high throughput format. The present study was conducted within the framework of the EU ChemScreen-project. It (1) enlarges the original number of test-compounds from 17 to now 80, (2) introduces a new classification scheme and (3) anchors the results against a prediction scheme based on structural features of chemicals. The assay is applicable as stand-alone for priority setting or in a test battery.

摘要

ReProGlo检测法于2009年开发,通过使用基于干细胞的体外系统来预测药物和化学物质的胚胎毒性潜力。它利用荧光素酶报告基因来检测药物诱导的经典Wnt/β-连环蛋白信号通路的变化,该信号通路参与早期胚胎发育的调节。它允许以高通量形式同时测定细胞活力和荧光素酶报告基因活性。本研究是在欧盟ChemScreen项目的框架内进行的。它(1)将测试化合物的原始数量从17种增加到现在的80种,(2)引入了一种新的分类方案,(3)根据化学物质的结构特征将结果与预测方案进行对照。该检测法可单独用于确定优先级或用于测试组合。

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