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|Title:||Hepatotoxicity Screening Taking a Mode-Of-Action Approach Using HepaRG Cells and HCA|
|Authors:||LANDESMANN Brigitte; HARRIS Georgina; LISKA Roman; WHELAN Maurice|
|Other Contributors:||MENNECOZZI MILENA|
|Citation:||ALTEX-Proceedings vol. 1 no. 1 p. 193-204|
|Publisher:||SPRINGER SPEKTRUM AKAD VERLAG|
|Type:||Articles in periodicals and books|
|Abstract:||The liver is central to the metabolism of xenobiotics. Evaluating the risk of liver toxicity is a major issue and there is still no established in vitro screening strategy to reliably identify potentially hepatotoxic chemicals. In the approach described here, a mode-of-action targeted analysis of the literature has been used to identify toxicity pathways and the key biological events associated with them. This knowledge has then been used to design a multi-parametric high throughput screening based on the quantification of fluorescently stained biomarkers expressed by treated HepaRG cells. Quantitative high throughput screening was employed using a 96-well plate format, which facilitated the testing of a set of 92 reference chemicals with known hepatotoxic activity. We exposed HepaRG cells to 16-point serial concentrations to generate dose-response profiles. By determining the POD (point of departure), the test chemicals were then associated with different mode-of-action based categories.|
|JRC Directorate:||Institute for Health and Consumer Protection Historical Collection|
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