BlueScreen HC is the latest innovative assay from Gentronix Ltd. to use genetically modified, human-derived cells to detect the genotoxic effects of compounds. The new assay builds flexibility into the use of GADD45a assays for pharmaceutical, personal care and consumer product testing.
Originally used for the highly successful GreenScreen® HC assay, p53-competent Human TK6 cells have now been modified to report expression of the GADD45a gene which occurs as a result of genotoxic damage using an alternative reporter construct. Whereas GreenScreen uses fluorescence from Green Fluorescent Protein (GFP) to signal GADD45a expression, the BlueScreen HC assay utilizes a luciferase from the marine copepod Gaussia princeps to generate a luminescent output that delivers both high specificity and high sensitivity, and also helps to reduce problems due to autofluorescence.
The addition of this alternative reporter construct builds flexibility into the choice of assay for the customer by extending the licensed range of applications for the GADD45a reporter assay to include, for example, flavours, fragrances and taste enhancers (FFTE). FFTE’s in personal care, cosmetics or consumer products can now be screened for genotoxicity in the same way as other components, giving greater consistency of results and convenience to the developer.
The first paper on the use of BlueScreen HC entitled “Development of a high-throughput Gaussia luciferase reporter assay for the activation of the GADD45a gene by mutagens, promutagens, clastogens, and aneugens” has been accepted for publication in the Journal of Biomolecular Screening. The conclusion of this peer reviewed paper is that BlueScreen HC was as effective as GreenScreen HC in producing positive results for all classes of genotoxicity, and negative results for all non-genotoxins tested.
About the GADD45a Gene
GADD45a plays an important role in mediating the adaptive response to genotoxic stress. The patented system used in BlueScreen HC and GreenScreen HC incorporates complex regulatory elements to enable a faithful GADD45a response. The assay generates positive results for direct-acting mutagens, clastogens, as well as aneugens, and topoisomerase and polymerase inhibitors. Importantly, correct negative results are produced for non-genotoxic compounds, many of which give misleading positive results in other in vitro genotoxicity tests. A metabolic activation protocol using rodent S9 liver extract extends the range of compounds detected to include genotoxic metabolites.
Other papers on BlueScreen HC, both by Gentronix and by independent organisations, will follow.
About Gentronix
Genotoxins are chemicals that can damage DNA, and may be carcinogens. Gentronix Ltd provides genotoxicity screening services for companies who develop new compounds in fields such as pharmaceuticals, agrichemicals, flavours and fragrances, personal care and consumer products.
In addition to conventional genotoxicity testing, Gentronix uses its own patented assays, BlueScreen™ HC and GreenScreen® HC, which use human cells that give a sensitive and specific response when a chemical damages or interferes with its DNA.
www.gentronix.co.uk
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