Spiral Salmonella assay: validation against the standard pour-plate assay.
The spiral Ames assay, an automated approach to bacterial mutagenicity testing which simplifies the test procedure and reduces the amount of drug required to generate mutagenic dose-response information, has been evaluated and validated for routine screening. The spiral plater delivers the Salmonella bacteria, exogenous metabolic activation system and drug to the surface of a rotating agar plate one on top of another in such a way that a uniform density of bacteria is exposed to a logarithmically decreasing volume of drug. Following an incubation of 48 hr at 37 degrees C, the plates are scanned by a laser counter, and the data are subjected to a computerized analysis. Petri plates of 15 cm diameter were used to provide a concentration range of about 250-fold per plate. The Salmonella were concentrated 20-fold to increase sensitivity. Thirty-eight compounds from a variety of chemical classes, including both pharmaceuticals and known mutagens of moderate to strong potency, were tested in both the spiral and the standard pour-plate assays. There was overall test agreement on positive or negative results for 82% of the compounds tested. When only the results from strains TA98 plus TA100 were considered, the agreement was 87%. When positive results were obtained, the fold increase over vehicle control was on average twice as great for the spiral assay compared to the pour-plate assay. It was concluded that the two assay procedures generally provided comparable results, with the spiral assay being somewhat more sensitive in terms of dose-response than the pour-plate assay.
Diehl
M
M
Genetic Toxicology Laboratory, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005069:Evaluation Studies as Topic; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000295:instrumentation* / Q000379:methods; D009153:Mutagens / Q000494:pharmacology; D051381:Rats; D012015:Reference Standards; D012486:Salmonella typhimurium / Q000187:drug effects*; D012680:Sensitivity and Specificity; D013045:Species Specificity
D009153:Mutagens