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High‐Content Analysis/Screening for Predictive Toxicology: Application to Hepatotoxicity and Genotoxicity
Author(s) -
Persson Mikael,
Løye Anni F.,
Jacquet Mélanie,
Mow Natacha S.,
Thougaard Annemette V.,
Mow Tomas,
Hornberg Jorrit J.
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12200
Subject(s) - micronucleus test , drug , toxicity , high content screening , drug discovery , genotoxicity , pharmacology , drug development , computational biology , toxicology , medicine , chemistry , biology , bioinformatics , cell , biochemistry
Abstract High‐content imaging/analysis has emerged as a powerful tool for predictive toxicology as it can be used for identifying and mitigating potential safety risks during drug discovery. By careful selection of end‐points, some cellular assays can show better predictivity than routine animal toxicity testing for certain adverse events. Here, we present the perhaps most utilized high‐content screening assays for predictive toxicology in the pharmaceutical industry. Multi‐parametric imaging of cell health in simple and cost‐effective model systems can be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and imaging of bile salt transport inhibition in sandwich‐cultured hepatocytes can be used to predict cholestasis‐inducing compounds. Imaging of micronuclei formation in simple cell models can be used to detect genotoxic potential and elucidate anuegenic or clastogenic mode of actions. The hope is that application of these relatively predictive assays during drug discovery will reduce toxicity and safety‐related attrition of drug development programmes at later stages.