Research output: Contribution to Journal/Magazine › Journal article
Research output: Contribution to Journal/Magazine › Journal article
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TY - JOUR
T1 - The GreenScreen genotoxicity assay : a screening validation programme.
AU - Cahill, P. A.
AU - Knight, A. W.
AU - Billinton, N.
AU - Barker, M. G.
AU - Walsh, L.
AU - Keenan, P. O.
AU - Williams, C. V.
AU - Tweats, D. J.
AU - Walmsley, R. M.
PY - 2004/3
Y1 - 2004/3
N2 - A yeast (Saccharomyces cerevisiae) DNA repair reporter assay termed the GreenScreen® assay (GSA) is described. This is a novel, cost-effective genotoxicity screen, developed to provide a pre-regulatory screening assay for use by the pharmaceutical industry and in other applications where significant numbers of compounds need to be tested. It provides a higher throughput and a lower compound consumption than existing eukaryotic genotoxicity assays and is sensitive to a broad spectrum of mutagens and, importantly, clastogens. We describe a simple, robust assay protocol and a validation study. The end-point of the test reflects the typically eukaryotic chromosomes and DNA metabolizing enzymes of yeast. The capacity for metabolic activation (MA) in yeast is limited compared with the mammalian liver or its extracts, but the assay does detect a subset of compounds that would require MA in existing genotoxicity tests. The GSA detects a different spectrum of compounds to bacterial genotoxicity assays and thus, together with an in silico structure–activity relationship (SAR) screen, and possibly a high throughput bacterial screen, would provide an effective preview of the regulatory battery of genotoxicity tests.
AB - A yeast (Saccharomyces cerevisiae) DNA repair reporter assay termed the GreenScreen® assay (GSA) is described. This is a novel, cost-effective genotoxicity screen, developed to provide a pre-regulatory screening assay for use by the pharmaceutical industry and in other applications where significant numbers of compounds need to be tested. It provides a higher throughput and a lower compound consumption than existing eukaryotic genotoxicity assays and is sensitive to a broad spectrum of mutagens and, importantly, clastogens. We describe a simple, robust assay protocol and a validation study. The end-point of the test reflects the typically eukaryotic chromosomes and DNA metabolizing enzymes of yeast. The capacity for metabolic activation (MA) in yeast is limited compared with the mammalian liver or its extracts, but the assay does detect a subset of compounds that would require MA in existing genotoxicity tests. The GSA detects a different spectrum of compounds to bacterial genotoxicity assays and thus, together with an in silico structure–activity relationship (SAR) screen, and possibly a high throughput bacterial screen, would provide an effective preview of the regulatory battery of genotoxicity tests.
U2 - 10.1093/mutage/geh015
DO - 10.1093/mutage/geh015
M3 - Journal article
VL - 19
SP - 105
EP - 119
JO - Mutagenesis
JF - Mutagenesis
SN - 1464-3804
IS - 2
ER -