Evaluation of the GADD45α-GFP GreenScreen HC assay for rapid and reliable in vitro early genotoxicity screening.
Twenty-two of Galderma's proprietary compounds were tested in the GADD45α-GFP 'GreenScreen HC' assay (GS), the SOS-ChromoTest and the Mini-Ames to evaluate GSs performance for early genotoxicity screening purposes. Forty more characterized compounds were also tested, including antibiotics: metronidazole, clindamycin, tetracycline, lymecycline and neomycin; and catecholamines: resorcinol mequinol, hydroquinone, one aneugen carbendazim, one corticoid dexamethasone, one peroxisome proliferator-activated receptor rosiglitazone, one pesticide carbaryl and two further proprietary molecules with in vitro genotoxicity data. With proprietary molecules, this study concluded that the GS renders the SOS-ChromoTest obsolete for in vitro screening. The GS confirmed all results of the Mini-Ames test (100% concordance). Compared with the micronucleus test, the GS showed a concordance of 82%. With known compounds, the GS ranked the potency of positive results for catecholamines in accordance with other genotoxicity tests and showed very reproducible results. It confirmed positive results for carbendazim, for tetracycline antibiotics and for carbaryl. The GS produced negative results for metronidazole, a nitroreduction-specific bacterial mutagen, for dexamethasone (a non-genotoxic apoptosis inducer), for rosiglitazone (a GADD45γ promoter inducer) and for clindamycin and neomycin (inhibitors of macromolecular synthesis in bacteria). As such, the GS appears to be a reproducible, robust, specific and sensitive test for genotoxicity screening.
Galderma R&D, Les Templiers, Route des Colles BP87, F-06902, Sophia-Antipolis, France.
Anne-Pascale
AP
Luzy
Nicolas
N
Orsini
Jean-Michel
JM
Linget
Guy
G
Bouvier
D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D055772:Green Chemistry Technology / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D049452:Green Fluorescent Proteins; D009153:Mutagens; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins