Non-breeding-test methods for dominant skeletal mutations shown by ethylnitrosourea to be easily applicable to...

Skeletons of (C3H X 101)F1 mice have been examined in earlier studies of the induction of dominant skeletal mutations. The present experiment was done to determine whether the same criteria used to identify mutations in (C3H X 101)F1 mice could be applied to the offspring collected in specific-locus experiments. Offspring were obtained from an experiment of Hitotsumachi et al. in which (101 X C3H)F1 male mice were exposed to 0, 300 mg/kg or 400 mg/kg of ethylnitrosourea (ENU) injected i.p. in exposures of 100 mg/kg administered 7 days apart. The 3 skeletal non-breeding-test (NBT) methods were applied in evaluating skeletons. The frequencies of presumed dominant skeletal mutations found following exposure of stem-cell spermatogonia to 0, 3 X 100 mg/kg, and 4 X 100 mg/kg of ENU were 2/374, 10/243, and 10/180, respectively. At each exposure level there is a highly statistically significant increase over the control. At the higher exposure, the induced presumed mutation frequency is 5.0% and the induced frequency of presumed mutations likely to be of clinical importance is 4.5%. The indices of mutation were 0% in the control, 11.5% in the 300 mg/kg group, and 12.4% in the 400 mg/kg group. These results show that the skeletal NBT methods can easily be combined with specific-locus experiments to increase the yield of data useful in estimating genetic risk. It appears that the induction of dominant skeletal mutations by ENU is reasonably similar when measured in specific-locus or (C3H X 101)F1 offspring.