C - Chemistry – Metallurgy – 12 – Q
Patent
C - Chemistry, Metallurgy
12
Q
C12Q 1/18 (2006.01) C12Q 1/68 (2006.01)
Patent
CA 2523610
Disclosed herein is a novel forward mutation assay based on 5-fluorouracil (5- FU) resistance which utilizes a strain of Salmonella typhimurium derived from the Ames strain TA100. More specifically, the invention provides a high throughput alternative to the standard Ames mutation assay for the evaluation of the genotoxicity activity of compounds during an early stage of the drug development process. The invention also identifies the upp locus as a mutational target that is capable of detecting a diverse spectrum of mutagenic events and further describes a S. typhimurium tester strain, designated FU100 (his+, rfa, .DELTA.uvrB, pkM101, 5-fluorouridine resistant) for use in the assay of the invention.
L'invention concerne un essai de mutation directe fondé sur la résistance au 5-fluorouracile (5-FU) mettant en oeuvre une souche de <i>Salmonella typhimurium</i> dérivée de la souche Ames TA100. Plus précisément, l'invention concerne une alternative à rendement élevé à l'essai de mutation normalisé Ames destiné à l'évaluation de l'activité de la génotoxicité de composés pendant une étape précoce du processus de développement de médicament. L'invention concerne également l'identification du locus <i>upp</i> comme une cible mutationnelle, capable de détecter un autre spectre d'événements mutagéniques, ainsi qu'une souche test de <i>S. typhimurium </i>, désignée par FU100 (<i>his+, rfa,</i> ?<i>uvrB</i>, pkM101, résistant à la 5-fluorouridine) à utiliser dans l'essai selon l'invention.
Glaab Warren E.
Miller Judith E.
Skopek Thomas R.
Vlasakova Katerina
Merck & Co. Inc.
Merck Sharp & Dohme Corp.
Norton Rose Or S.e.n.c.r.l. S.r.l./llp
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