An analysis of results from 305 compounds tested with the yeast RAD54-GFP genotoxicity assay (GreenScreen GC)-including relative predictivity of regulatory tests and rodent carcinogenesis and performance with autofluorescent and coloured compounds.
Data from 305 non-proprietary compounds tested using the yeast RAD54-GFP (Green Fluorescent Protein) assay, GreenScreen GC, are presented, together with a detailed comparison with results from in vitro and in vivo genotoxicity tests and rodent carcinogenesis. In addition, observations on reproducibility and the performance of the test with autofluorescent and coloured compounds are described. Like the Ames test, the GreenScreen assay is shown to exhibit high specificity (82%), meaning that compounds with positive results are very likely to be genotoxic carcinogens. This is in contrast to mammalian cell tests established for use in regulatory testing that provide disappointingly low specificity and the inevitable generation of confounding false positive data. The analysis confirmed the observations of earlier studies, showing that a combination of an Ames test (or surrogate) with the yeast test provides high specificity as well as high sensitivity in the identification of rodent carcinogens.
Knight
Andrew W
AW
Gentronix Ltd, CTF Building, 46 Grafton Street, Manchester M13 9NT, UK. andre.knight@gentronix.co.uk
Billinton
N
N
Cahill
P A
PA
Scott
A
A
Harvey
J S
JS
Roberts
K J
KJ
Tweats
D J
DJ
Keenan
P O
PO
Walmsley
R M
RM
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004396:Coloring Agents / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects; D009152:Mutagenicity Tests / Q000592:standards; D011401:Promoter Regions, Genetic; D051381:Rats; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis*; D012680:Sensitivity and Specificity
D002273:Carcinogens; D004396:Coloring Agents; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes