Evaluation of the GreenScreen GADD45alpha-GFP indicator assay with non-proprietary and proprietary compounds

Mutat Res. 2009 Jan;672(1):10-6. doi: 10.1016/j.mrgentox.2008.08.019. Epub 2008 Sep 4.

Abstract

The GreenScreen GADD45alpha indicator assay has been assessed for its concordance with in vitro genotoxicity and rodent carcinogenicity bioassay data. To test robustness, sensitivity, and specificity of the assay, 91 compounds with known genotoxicity results were screened in a blinded manner. Fifty seven of the compounds were classified as in vitro genotoxic whereas 34 were non-genotoxic. Out of the 91 compounds, 50 had been tested in 2-year carcinogenicity assays, with 33 identified to be rodent carcinogens and 17 non-carcinogens. Gadd45alpha assay sensitivity and specificity for genotoxicity was 30% and 97%, respectively (17/57 and 33/34), whereas its sensitivity and specificity for rodent carcinogenicity was 30% and 88%, respectively (10/33 and 15/17). Gadd45alpha assay genotoxicity results from this validation study exhibited a high concordance with previously published results as well as for compound test results generated at two different sites (91%, 19/21), indicating that the assay is both robust and reproducible. In conclusion, results from this blinded and independent validation study indicate that the GreenScreen GADD45 indicator assay is reproducible and reliable with low sensitivity and high specificity for identifying genotoxic and carcinogenic compounds.

MeSH terms

  • Animals
  • Biological Assay
  • Carcinogens
  • Cell Cycle Proteins / biosynthesis*
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Green Fluorescent Proteins / metabolism*
  • Humans
  • Mice
  • Micronucleus Tests / methods
  • Mutagenicity Tests / methods*
  • Mutagens
  • Nuclear Proteins / biosynthesis*
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Carcinogens
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Gadd45a protein, mouse
  • Mutagens
  • Nuclear Proteins
  • Green Fluorescent Proteins