title: Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: an interlaboratory study.
abstract: Experimental features of a positive selection transgenic mouse mutation assay based on a lambda lacZ transgene are considered in detail, with emphasis on results using germ cells as the target tissue. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined, with the goal of identifying sources of excess variation in the observed mutant frequencies. The sources include plate-to-plate (within packages), package-to-package (within animals), and animal-to-animal variability. Data from five laboratories are evaluated in detail. Results suggest only scattered patterns of excess variability below the animal-to-animal level, but, generally, significant excess variability at the animal-to-animal level. Using source of variability analyses to guide the choice of statistical methods, control-vs-treatment comparisons are performed for assessing the male germ cell mutagenicity of ethylnitrosourea (ENU), isopropyl methanesulfonate (iPMS), and methyl methanesulfonate (MMS). Results on male germ cell mutagenesis of ethyl methanesulfonate (EMS) and methylnitrosourea (MNU) are also reported.
authors.affiliation: Department of Statistics, University of South Carolina, Columbia 29208, USA. piegorsc@stat.sc.edu
authors.forename: W W
authors.initials: WW
authors.lastname: Piegorsch
authors.forename: A C
authors.initials: AC
authors.lastname: Lockhart
authors.forename: G J
authors.initials: GJ
authors.lastname: Carr
authors.forename: B H
authors.initials: BH
authors.lastname: Margolin
authors.forename: T
authors.initials: T
authors.lastname: Brooks
authors.forename: G R
authors.initials: GR
authors.lastname: Douglas
authors.forename: U M
authors.initials: UM
authors.lastname: Liegibel
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: V
authors.initials: V
authors.lastname: Thybaud
authors.forename: J H
authors.initials: JH
authors.lastname: van Delft
authors.forename: N J
authors.initials: NJ
authors.lastname: Gorelick
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D007391:International Cooperation; D007753:Laboratories; D007763:Lac Operon; D008297:Male; D008698:Mesylates / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D008698:Mesylates; D009153:Mutagens; D008770:Methylnitrosourea; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea; C002531:isopropylmethanesulfonate