ToxTracker® Assay for Mechanistic Insight into Genotoxic Properties of Compounds

ToxTracker® can be particularly useful identifying genotoxic and non-genotoxic modes of action including oxidative stress, protein misfolding, and general cellular stress. The unique combination of fluorescent reporter genes allows for highly accurate identification of genotoxic carcinogens, and the induction of GFP reporters by test compounds is efficiently measured across a broad concentration range using flow cytometry, resulting in quantitative data on dose-response relationships. This feature makes ToxTracker® ideal to be used to quickly and accurately screen out genotoxic compounds or as a GLP-compliant assay to support de-risk of adverse finding in regulatory assays.

Diagram depicting the markers ToxTracker can identify that reveal genotoxic modes of action as well as non-genotoxic modes of action including DNA, protein, and oxidative damage

The unique assay combines 6 fluorescent reporter cell lines to discriminate between induction of DNA damage, activation of p53, induction of oxidative stress and protein damage. Their collective induction profile provides mechanistic insight into specific genotoxic properties of compounds.

 

ToxTracker® Assay Reporters

Diagram of ToxTracker’s six fluorescent assay reporter cells and the genotoxic and non-genotoxic Modes of Action (MoA) the assay predicts

 

Key Benefits

  • Mechanistic insight into genotoxicity
  • Unsurpassed sensitivity (94%) and specificity (95%)
  • Predictor for regulatory in vitro and in vivo assays
  • Rapid and reliable
Test Name Sensitivity (%) Specificity (%)
ToxTracker® 94 95
Chromosome aberrations 79 55
Mammalian mutation 81 48
Bacterial reversion (Ames) 60 77
Micronucleus test 79 54

 

Applications in the Genotoxicity Assessment

  • Early non-regulatory preclinical development phase of pharmaceuticals applied as genotoxicity screen – ToxTracker® can predict with high accuracy the outcomes the regulatory in vitro battery of genotoxicity tests (positive in mutation or chromosome damage tests)
  • GLP-compliant assay as follow up of the regulatory in vitro battery of genotoxicity assays to provide insight into MOA of genotoxic compounds – This information can be used in a weight of evidence approach to claim safety threshold limit of exposure
  • Prescreen or as mechanistic follow up of the regulatory in vitro genotoxicity tests for cosmetic ingredients and final products
  • Mechanistic studies and read across approaches for retesting of marketed chemicals under REACH and novel substances
  • In vitro indicator test for numerous non-genotoxic mechanisms of toxicity that are associated with increased carcinogenicity hazard