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 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.
Krewski
D
D
Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.
Leroux
B G
BG
Bleuer
S R
SR
Broekhoven
L H
LH
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
D009153:Mutagens