Mutations in the F1 generation of mice.

The occurrence of induced dominant genetic damage can be measured by comparing mutation frequencies in first generation descendants from treated and untreated populations, but for many characters, it is difficult to distinguish between the effects of newly occurring genetic damage and the within-strain variation. This problem has been solved for skeletal abnormalities and for dominant cataract mutations. The skeleton was chosen because it is formed over an extended period of development and is, therefore, presumably subject to modification by gene action expressed during a wide range of time. The direct comparability of the genetic endpoint of mice and men was one aspect which led us to initiate a systematic investigation of the induction of dominant cataracts, an opacity of the lens, in the mouse. Another aspect was that Ehling (1976) developed a concept for the direct estimation of the risk of radiation induced genetic damage to the human population expressed in the first generation, based on the induction of dominant mutations in mammals. Using the direct method we estimated that 20-50 dominant radiation induced mutations would be expected in 19,000 offspring born to parents exposed in Hiroshima and Nagasaki, but only a small proportion of these mutants would have been detected with the techniques used in the population study. The detection of dominant cataract mutations can be combined with the detection of recessive specific locus mutations in mice. The specific locus method consists of mating treated wild-type mice to mice homozygous for seven recessive marker loci and scoring in the first generation offspring for mutations at any of these marked loci. The advantage of a combined investigation of dominant cataract mutations and specific locus mutations is at least three-fold: 1st The number of scorable mutations is increased by a factor of four. 2nd The combined investigation allows the comparison of the mutation frequency of selected and unselected loci. 3rd In the same experiment the frequency of mutations with a dominant and a recessive mode of expression can be compared. The specific locus method was used to investigate the effects of chemicals and radiation on the mutation frequency with respect to the following factors: differential spermatogenic response; changes of the mutation spectrum with different doses of chemicals; comparison of the mutation rates under different treatment conditions; sex and strain differences. Using this method we will demonstrate the possibility to quantify the genetic risk of chemical mutagens. In addition, the per locus ratio of radiation induced dominant to recessive mutations in spermatogonia of the mouse is approximately 1:10.(ABSTRACT TRUNCATED AT 400 WORDS)