title: Modeling the Ames Salmonella/microsome assay.
abstract: Of the many short-term tests for mutagenicity that have been proposed in recent years, the Ames Salmonella/microsome assay is the single most widely used and most thoroughly validated in vitro test system. This assay uses cells cultured in a soft agar containing a trace amount of histidine to allow growth of auxotrophic bacteria, and is designed to detect reverse mutations from auxotrophic cells to histidine-independent prototrophic cells. In this paper, statistical models that have been proposed for the analysis of Ames test data are reviewed, including those of a mechanistic and empirical nature. An extension to the class of biologically based models derived by Margolin, Kaplan, and Zeiger (1981, Proceedings of the National Academy of Sciences 78, 3779-3783) is proposed by allowing for diffusion of histidine within the plate agar. Quasi-likelihood methods for estimating the model parameters are presented, and applied to 1,120 data sets from a recent collaborative trial sponsored by the International Programme on Chemical Safety.
authors.affiliation: Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.
authors.forename: D
authors.initials: D
authors.lastname: Krewski
authors.forename: B G
authors.initials: BG
authors.lastname: Leroux
authors.forename: S R
authors.initials: SR
authors.lastname: Bleuer
authors.forename: L H
authors.initials: LH
authors.lastname: Broekhoven
mesh_terms: D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D008433:Mathematics; D008862:Microsomes, Liver / Q000378:metabolism*; D015233:Models, Statistical; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
chemical_list: D009153:Mutagens