High-throughput screening for analysis of in vitro toxicity

  • Willem G. E. J. Schoonen
  • Walter M. A. Westerink
  • G. Jean Horbach
Part of the Experientia Supplementum book series (EXS, volume 99)


The influence of combinatorial chemistry and high-throughput screening (HTS) technologies in the pharmaceutical industry during the last 10 years has been enormous. However, the attrition rate of drugs in the clinic due to toxicity during this period still remained 40-50%. The need for reduced toxicity failure led to the development of early toxicity screening assays. This chapter describes the state of the art for assays in the area of genotoxicity, cytotoxicity, carcinogenicity, induction of specific enzymes from phase I and II metabolism, competition assays for enzymes of phase I and II metabolism, embryotoxicity as well as endocrine disruption and reprotoxicity. With respect to genotoxicity, the full Ames, Ames II, Vitotox™, GreenScreen GC, RadarScreen, and non-genotoxic carcinogenicity assays are discussed. For cytotoxicity, cellular proliferation, calcein uptake, oxygen consumption, mitochondrial activity, radical formation, glutathione depletion as well as apoptosis are described. For high-content screening (HCS), the possibilities for analysis of cytotoxicity, micronuclei, centrosome formation and phospholipidosis are examined. For embryotoxicity, endocrine disruption and reprotoxicity alternative assays are reviewed for fast track analysis by means of nuclear receptors and membrane receptors. Moreover, solutions for analyzing enzyme induction by activation of nuclear receptors, like AhR, CAR, PXR, PPAR, FXR, LXR, TR and RAR are given.


HepG2 Cell Luteinizing Hormone Chinese Hamster Ovary Cell Constitutive Androstane Receptor Endocrine Disruption 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Willem G. E. J. Schoonen
    • 1
  • Walter M. A. Westerink
    • 1
  • G. Jean Horbach
    • 1
  1. 1.Department of PharmacologyNV Organon (Schering- Plough)OssThe Netherlands

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