TY - JOUR
T1 - Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay
T2 - An interlaboratory study
AU - Piegorsch, Walter W.
AU - Lockhart, Ann C.
AU - Carr, Gregory J.
AU - Margolin, Barry H.
AU - Brooks, Terry
AU - Douglas, George R.
AU - Liegibel, Ute M.
AU - Suzuki, Takayoshi
AU - Thybaud, Véronique
AU - Van Delft, Joost H.M.
AU - Gorelick, Nancy J.
PY - 1997/2
Y1 - 1997/2
N2 - Experimental features of a positive selection transgenic mouse mutation assay based on a λlacZ 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.
AB - Experimental features of a positive selection transgenic mouse mutation assay based on a λlacZ 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.
KW - Ethylnitrosourea
KW - Extra-binomial variability
KW - Hierarchical sampling
KW - Isopropyl methanesulfonate
KW - Methyl methanesulfonate
KW - Mutagenicity
KW - Positive selection assay
KW - Statistical method
KW - Transgene
KW - Transgenic mouse
UR - http://www.scopus.com/inward/record.url?scp=17344388103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17344388103&partnerID=8YFLogxK
U2 - 10.1016/S1383-5718(96)00123-4
DO - 10.1016/S1383-5718(96)00123-4
M3 - Article
C2 - 9057887
AN - SCOPUS:17344388103
VL - 388
SP - 249
EP - 289
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
SN - 1383-5718
IS - 2-3
ER -