SOURCES OF VARIABILITY IN TUMOR INCIDENCE IN LONG TERM RODENT STUDIES

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The mouse epididymal sperm anueploidy (mESA) assay using 3-chromosome fluorescence in situ hybridization (FISH) was recently developed for assessing the aneugenic potential of chemicals on male germ cells. We investigated the factors affecting inter-scorer and inter-laboratory variability in response. We identified microscope scoring criteria as the major source of interlaboratory variation, which emphasizes the importance of strict technical controls for the assay. Our findings suggest that observed factors of two differences between scorers, samples, and treatment groups are currently within the normal variation of the mESA assay, and differences of this magnitude should be viewed with caution without independent confirmation. During the past year, we also completed the development of statistical models to take into account animal-to-animal and time-related variability in the incidence and multiplicity of skin papilloma in Tg.AC mouse bioassays. Another study is investigating the association between renal tubule cell adenoma and the severity of chronic progressive nephropathy (CPN) in control male Fischer 344 rats. Preliminary results suggest that rats with more severe CPN have a slightly increased risk of developing kidney tubular adenoma relative to equivalently-aged animals with lesser CPN severity.