GADD45a-GFP GreenScreen HC genotoxicity screening assay.
BACKGROUND
Genetic toxicology is getting very interesting. The International Conference on Harmonisation has drafted new guidance that allows for the registration of pharmaceuticals without the submission of data from in vitro mammalian genotoxicity tests (in vitro micronucleus test, chromosomal aberrations, mouse lymphoma assay). These tests often produce falsely positive predictions of genotoxic carcinogenicity.


OBJECTIVE
This article reviews the properties of the Gadd45a-GFP (green fluorescent protein) assay, for which positive results appear to provide more reliable predictions of genotoxic carcinogenicity. The criteria for assessment of genotoxicity assays are reviewed. Consideration is given to the value of genotoxicity hazard assessment early in pharmaceutical discovery.


METHODS
Peer-reviewed data have been reviewed, as well as information contributed to the public domain through conference presentations.


CONCLUSIONS
The Gadd45a assay is increasingly used as a screening tool, and has utility in the prioritisation of Ames-negative compounds prior to in vivo genotoxicity assessment.
Walmsley
Richard M
RM
Gentronix Ltd, CTF Building, 46 Grafton Street, Manchester M13 9NT, UK. richard.walmsley@manchester.ac.uk
D018797:Cell Cycle Proteins / Q000235:genetics*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009687:Nuclear Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000187:drug effects*; D015203:Reproducibility of Results; D018570:Risk Assessment; D014158:Transcription, Genetic / Q000187:drug effects*; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D049452:Green Fluorescent Proteins; D009153:Mutagens; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins