A cell-based, multiparametric sensor approach characterises drug-induced cytotoxicity in human liver HepG2 cells
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2297361
Author(s) Seeland, Swen; Török, Michael; Kettiger, Helene; Treiber, Alexander; Hafner, Mathias; Huwyler, Jörg
Author(s) at UniBasel Huwyler, Jörg
Kettiger, Helene
Year 2013
Title A cell-based, multiparametric sensor approach characterises drug-induced cytotoxicity in human liver HepG2 cells
Journal Toxicology in vitro
Volume 27
Number 3
Pages / Article-Number 1109-20
Keywords HepG2, Cytotoxicity, Metabolic stress, Cytosensor, Mitochondrial respiration, Respiratory stress, Drug-induced liver injury (DILI)
Abstract

Drug-induced toxicity is of considerable concern in drug discovery and development, placing emphasis on the need for predictive in vitro technologies that identify potential cytotoxic side effects of drugs. A label-free, real-time, multiparametric cytosensor system has therefore been established for in vitro assessment of drug-induced toxicity. The system is based on monitoring cellular oxygen consumption, acidification and impedance of human hepatocarcinoma-derived HepG2 cells. The read-out derived from the multiparametric cytosensor system has been optimised and permits sensitive, reliable, and simultaneous recording of cell physiological signals, such as metabolic activity, cellular respiration and morphological changes and cell adhesion upon exposure to a drug. Analysis of eight prototypic reference drugs revealed distinct patterns of drug-induced physiological signals. Effects proved to be rigidly concentration-dependent. Based on signal patterns and reversibility of the observed effects, compounds could be classified based as triggering mechanisms of respiratory or metabolic stress or conditions leading to cell death (necrosis-like and apoptosis-like). A test-flag-risk mitigation strategy is proposed to address potential risks for drug-induced cytotoxicity.

Publisher Elsevier
ISSN/ISBN 0887-2333
URL http://www.ncbi.nlm.nih.gov/pubmed/23416262
edoc-URL http://edoc.unibas.ch/dok/A6211984
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.tiv.2013.02.001
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/23416262
ISI-Number WOS:000317446500015
Document type (ISI) Journal Article
 
   

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