Phenotypic Variation within Genetically Homogeneous Populations: Responsiveness to Toxicants
Phenotypic variation in mammalian populations reflects not only genetic variability due to allelic and chromosomal differences but also the expressivity of genotypes. Expressivity is defined as the range of phenotypes expressed by a given genotype under any given set of environmental conditions or over a range of environmental conditions.1 This type of phenotypic variation and its possible physiological and molecular bases are the subject of this discussion. The strain-associated susceptibility to tissue-specific lesions, which also is reflected in the responsiveness to toxic insults, is an example of this type of variation. It is of practical relevance to risk assessment if only because sample sizes and dose levels in subchronic and chronic toxicity assays depend on the relative responsiveness of the inbred or F-1 hybrid test animal population used. This type of phenotypic variation is present in genetically heterogeneous populations but there it is inextricably confounded with the variation due to genetic differences. Therefore, its molecular and physiological components can only be defined in genetically homogeneous populations, e.g., inbred strains or their F-l hybrids. Once defined, however, they can be incorporated in the design of studies using genetically heterogeneous test animal populations.
KeywordsBackground Genome Hepatocellular Adenoma Hybrid Mouse Toxic Insult Glandular Hyperplasia
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- 1.C. King and W.D. Stansfield, “A Dictionary of Genetics,” Oxford University Press, New York (1985).Google Scholar
- 13.G.L. Wolff and R.L. Morrissey, Increased responsiveness of lean pseudoagouti A vy /a female mice to lindane enhancement of lung and liver tumorigenesis, Proc. Am. Assn. Cancer. Res., 27:138 (1986).Google Scholar