Modeling the Ames Salmonella/microsome assay

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...

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Bibliographic Details
Published inBiometrics Vol. 49; no. 2; p. 499
Main Authors Krewski, D, Leroux, B G, Bleuer, S R, Broekhoven, L H
Format Journal Article
LanguageEnglish
Published United States 01.06.1993
Subjects
Animals
Biotransformation
Dose-Response Relationship, Drug
Mathematics
Microsomes, Liver - metabolism
Models, Statistical
Mutagenicity Tests - methods
Mutagens - metabolism
Mutagens - toxicity
Salmonella typhimurium - drug effects
Salmonella typhimurium - genetics
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ISSN0006-341X
DOI10.2307/2532562

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Summary: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.
ISSN:0006-341X
DOI:10.2307/2532562