Applicability domain of the GADD45a reporter assays: non-steroidal anti-inflammatory drugs do not produce misleading genotoxicity results
Toxicology Research Pub Date: 2013-06-24 DOI: 10.1039/C3TX50029B
Abstract
Increased expression of the GADD45a gene is a very specific biomarker of genotoxin exposure in TK6 cells, and has been exploited in green fluorescent protein and luciferase reporter genotoxicity assays. A recent European Food Safety Authority suggested that the GADD45a-reporter genotoxicity assays might produce misleading positive results for non-steroidal anti-inflammatory drugs. This study was conceived to test the hypothesis that these drugs should be excluded from the applicability domain of the TK6 cell GADD45a GreenScreen HC and BlueScreen HC reporter assays. Data from published screening and validation studies have been reviewed, and new test data have been generated from 20 NSAIDS, from both reporter assays, both in the presence and absence of metabolic activation. The data fail to support this hypothesis: the high specificity of the GADD45a reporter assays is maintained amongst NSAIDs.
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Journal Name：Toxicology Research
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CAS no.: 89640-58-4
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