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Validation of a Multiparametric, High-Content-Screening Assay for Predictive/Investigative Cytotoxicity: Evidence from Technology Transfer Studies and Literature Review

A multiparametric, live-cell, high-content-screening (HCS) cytotoxicity assay was first demonstrated in 2006 (Arch. Toxicol. 2006, 80, 580−604) to be highly concordant with human hepatotoxicity, including idiosyncratic hepatotoxicities and other target organ toxicities in contrast to historical assays. The success of the assay was attributed to its simultaneous measurement of multiple appropriate “cytobiomarkers”: use of human cells with xenometabolic competence for toxicities mediated by metabolites, 72 h exposure to enable expression of slower-acting toxicants, exposure to a wide-range of concentrations from 30- to 100-fold the efficacious concentration, and normalizing the in vitro cytotoxic concentration to an estimate of the in vivo concentration of exposure. An overwhelming volume of evidence has accumulated over the last 10 years to support this approach as necessary in predictive toxicology. Equivalent assays have now been successfully applied in ∼50 studies across a wide variety of toxicants, tox...

Authors:   Peter James O’Brien; Anna Edvardsson
Journal:   Chemical Research in Toxicology
Year:   2017
DOI:   10.1021/acs.chemrestox.6b00403
Publication date:   22-Feb-2017
Facts, background information, dossiers
  • metabolites
  • Expression
  • cells
  • Arch
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