A combined dominant
cataract-recessive specific locus mutation experiment for fractionated exposure to
ethylnitrosourea (2 X 80 mg/kg, 24-h fractionation interval) was designed to determine if lower doses of
ethylnitrosourea are more effective in inducing dominant
cataract mutations as suggested by previous results. This observation was not confirmed by the present experiment. The extensive, statistically more reliable specific locus results indicate an additive effect of fractionated
ethylnitrosourea treatment. A saturable repair system for
ethylnitrosourea-induced DNA damage has been previously documented (Karran et al., 1979; Sega et al., 1986; Van Zeeland et al., 1985). Two parameters inherent to a saturable system, the minimal time required for the saturated system to recover and the minimal dose to saturate the system are important, and results of experiments employing a fractionation exposure protocol must be interpreted relative to these two parameters. Longer fractionation intervals or smaller doses result in a reduced mutagenic effect. Due to the inherently lower experimental variability of the specific locus mutation assay as compared to the dominant
cataract assay, the specific locus assay is the test of choice to determine factors affecting the mammalian germ cell mutation rate. The dominant
cataract test requires a larger investment of experimental resources to achieve a comparable degree of accuracy. The dominant
cataract mutation test is important in assessing the mutation rate to dominant alleles in germ cells of mammals. Due to the immediate expression of the mutant phenotype in newly occurring dominant mutations, a dominant mutation assay screens a genetically relevant endpoint in an assessment of the mutagenic hazard for man in mouse experiments. A multi-endpoint design screening specific locus, dominant
cataract, and biochemical mutational endpoints (Ehling et al., 1985) allows a systematic comparison of mutagenic results for different classes of mutations in the same animals.