Low-Level Exposures To Chemical Carcinogens: Mutational End Points
The choice of a mutational end point has an important bearing on both: (1) extrapolation from relatively high doses in laboratory animals to the much lower doses that are typical in environmental situations and (2) extrapolation from laboratory test systems to humans. Extrapolation from relatively high doses to the low doses typical in environmental situations is dependent on the shape of the dose-response curve. In vivo mutagenesis in eukaryotes usually consists of describing the relation of exposure of the whole organism to the mutation frequency. This conventional approach has the effect of placing the entire organism in a “black box” in which there are no intermediate determinants between exposure of the entire organism and observed mutation frequency in succeeding generations. To avoid combining physiological differences with mutagenic differences, I will distinguish between the dose to the target of interest — DNA — and exposure of a whole organism. In previous publications (Lee, 1976, 1978 and 1983) we have discussed the partitioning of the exposure to genetic response curve into an exposure-dose response curve and a dose-genetic response curve. The importance of this partitioning is to enable one to study physiology separately from the mutation process.
KeywordsSpontaneous Mutant Reciprocal Translocation Chemical Carcinogen Ethyl Methanesulfonate Ethyl Methane Sulfonate
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