DOSE EFFECT RELATIONSHIPS OF GERM CELL MUTATIONS IN MICE
The toxicological literature is replete with thresholded phenomena, and traditional thinking about dose response relationships generally assumes a threshold until data indicate otherwise. In contrast, the experience with radiation mutagenesis has introduced theories and supporting data for the absence of a threshold. Chemical mutagens share the pharmacokinetics and metabolism of traditional toxins, as well as the potential for the stochastic inherently non-thresholded mechanism of radiation induction of mutations. Not surprisingly, there are strong differences of opinion as to whether, in the absence of data, one should assume a threshold or a non-thresholded response for the genotoxic effects of chemicals. For the clarification of these problems, there is no alternative at present to a case by case analysis based on the laborious acquisition of good dose response data. A threshold dose response relationship is one in which a range of subcritical dose is incapable of producing the specified response. The minimal dose that can elicit the response is the threshold dose. The different aspects of thresholds in chemical mutagenesis have been recently discussed in detail. In this paper two aspects of germ cell mutations in mice, which are relevant to the threshold problem, will be discussed: the effect of dose fractionation and the dose response of intergenic and intragenic mutations.
Bibliographic Reference: PROBLEMS OF THRESHOLD IN CHEMICAL MUTAGENESIS, 1984, PP. 15-25, PUBLISHED BY THE ENVIRONMENTAL MUTAGEN SOCIETY OF JAPAN
Record Number: 1989123068800 / Last updated on: 1987-01-01
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