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- Title
Analysis of 75 marketed pharmaceuticals using the GADD45a-GFP ‘GreenScreen HC’ genotoxicity assay.
- Authors
Hastwell, Paul W.; Webster, Thomas W.; Tate, Matthew; Billinton, Nicholas; Lynch, Anthony M.; Harvey, James S.; Rees, Robert W.; Walmsley, Richard M.
- Abstract
The GADD45a-GFP (GreenScreen HC) reporter assay detects genotoxic damage in the human lymphoblastoid TK6 cell line and gives positive results for all classes of genotoxin, including mutagens, aneugens and clastogens. In this study, a collection of 75 marketed pharmaceuticals were tested in the assay. Compounds in the collection represent a broad range of chemical structures, pharmacologies and therapeutic indications, including neoplasia and viral infection where positive genotoxicity results are often associated with the pharmacological activity. Based on the results of this study, two main conclusions can be drawn: (i) the GreenScreen HC is more predictive of in vivo genotoxicity (88%) and genotoxic carcinogenicity (93%) data than the any of the other regulatory in vitro genotoxicity assay and (ii) no compounds were uniquely positive in the GADD45a-GFP assay. This analysis therefore provides additional evidence to support the use of the GADD45a-GFP assay as an effective tool either in early genotoxic liability identification or non-clinical safety assessment of candidate pharmaceuticals during development.
- Subjects
PHARMACODYNAMICS; DRUG analysis; GENETIC toxicology; LYMPHOBLASTOID cell lines; CELL lines
- Publication
Mutagenesis, 2009, Vol 24, Issue 5, p455
- ISSN
0267-8357
- Publication type
Article
- DOI
10.1093/mutage/gep029