title: Statistical analysis of lacZ mutant frequency data from MutaMouse mutagenicity assays.
abstract: Transgenic mouse assays have provided an unprecedented opportunity to study mutagenesis in diverse rodent tissues. In this article data from MutaMouse mutagenicity assays based on the Escherichia coli gene lacZ were analyzed systematically using liver and bone marrow as potential target tissues. Sources of variation, including plates (within packaging reactions), packaging reactions (within animals) and animals, were evaluated for extra-binomial variation. Although hardly any evidence of overdispersion was detected at the plate level, limited evidence of extra-binomial variation was observed at the packaging reaction level. There was, however, much stronger evidence of overdispersion at the animal level. Statistical tests for increasing trend in mutant frequency with increasing dose were also performed at the animal level. A significant increasing trend following exposure to N-nitrosodibenzylamine was detected in liver but not in bone marrow. A logistical model was used to further describe the dose-response relationship observed in N-nitrosodibenzylamine-treated liver tissue.
authors.affiliation: Department of Mathematics and Statistics, University of Windsor, Ontario, Canada. kfung@uwindsor.ca
authors.forename: K Y
authors.initials: KY
authors.lastname: Fung
authors.forename: G R
authors.initials: GR
authors.lastname: Douglas
authors.forename: D
authors.initials: D
authors.lastname: Krewski
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007763:Lac Operon / Q000187:drug effects*; D008099:Liver / Q000187:drug effects; D016015:Logistic Models; D051379:Mice; D008822:Mice, Transgenic; D015233:Models, Statistical; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests / Q000706:statistics & numerical data*; D009602:Nitrosamines / Q000008:administration & dosage; D015203:Reproducibility of Results; D019076:Transgenes / Q000187:drug effects
chemical_list: D009602:Nitrosamines; C015395:N-nitrosodibenzylamine