Title: Hepatotoxicity Screening Taking a Mode-Of-Action Approach Using HepaRG Cells and HCA
Authors: LANDESMANN BrigitteHARRIS GeorginaLISKA RomanWHELAN Maurice
Other Contributors: MENNECOZZI MILENA
Citation: ALTEX-Proceedings vol. 1 no. 1 p. 193-204
Publisher: SPRINGER SPEKTRUM AKAD VERLAG
Publication Year: 2012
JRC N°: JRC70162
ISSN: 2194-0479
URI: http://www.altex.ch/resources/193204_Mennecozzi3.pdf
http://publications.jrc.ec.europa.eu/repository/handle/JRC70162
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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