DOSE-DEPENDENT INDUCTION OF RECESSIVE MUTATIONS WITH N-ETHYL-N-NITROSOUREA IN PRIMORDIAL GERM-CELLS OF MALE-MICE

Using a specific locus test, we previously found that N-ethyl-N-nitros ourea (ENU) induces recessive mutations at a relatively high rate in m ale mouse primordial germ cells (PGC) at 8.5, 10.5 and 13.5 days of de velopment (G8.5, G10.5 and G13.5). A large difference was observed on the induced mutation rate between 30 and 50 mg/kg ENU in 10.5-day PGC. We therefore carried out specific locus tests to ascertain whether EN U induces recessive mutations in a dose-dependent manner in G8.5 and G 10.5 PGC. We also gave multiple doses of 25 mg/kg ENU using an 18-h in terval, the approximate doubling time of PGC at these developmental st ages, to test for an additive effect on the induced mutations rate. A dose-dependent induction of recessive mutations by ENU was observed in both G8.5 and G10.5 PGC, and multiple dosing of 25 mg/kg ENU showed a n additive effect. Comparing these results to data on spermatogonial s tem cells, we conclude the capacity to repair ENU-induced premutagenic damages is less effective in male mouse PGC at these developmental st ages than in spermatogonial stem cells.