THE INDUCTION OF RECESSIVE MUTATIONS IN MOUSE PRIMORDIAL GERM-CELLS WITH N-ETHYL-N-NITROSOUREA

A specific-locus test was carried out to examine the mutagenic activit y of N-ethyl-N-nitrosourea (ENU) on mouse primordial germ cells (PGC). Embryos of C3H/He mice were treated transplacentally with 30 or 50 mg ENU per kg of maternal body weight on day 8.5, 10.5, or 13.5 of gesta tion (G8.5 day, G10.5 day, or G13.5 day). Male and female mice that ha d been treated with ENU in embryonic stages were mated with female or male tester PW mice to detect recessive mutations induced in PGC. ENU induced recessive mutations at a relatively high rate in PGC at these developmental stages. The most sensitive stage was G10.5 day. On G8.5 day, the induced mutation rate in males and females was not significan tly different. Cluster mutations, which originate from the limited num ber of PGC and cell killing, were more frequently induced at an earlie r developmental stage. The induced mutation rate per unit dose of ENU (1 mg/kg) was higher in G8.5 and G10.5 day PGC than in stem-cell sperm atogonia. It can be concluded that mouse PGC are more sensitive than s tem-cell spermatogonia to the induction of recessive mutations by ENU.