Congenital malformations in the offspring of male mice treated with ethylnitrosourea at the embryonic stage.

Ethylnitrosourea (ENU) was i.p. injected into ICR female mice at 25 or 50 mg/kg on day 10 of gestation, and male newborns treated with ENU at the embryonic stage were obtained. The treated males were aged for 10 weeks and then mated to untreated females of the same strain. The male germ cells used in the copulation correspond to primordial germ cells (PGC) at the time of ENU treatment. The F1 offspring were sampled as fetuses on day 18 of gestation and inspected for external and skeletal malformations. Evidence of F1 teratogenesis due to the mutagenized PGC was obtained when the fetuses from the males treated with 25 mg ENU/kg were inspected the frequencies of skeletally malformed fetuses in the ENU-treated series and the control being, respectively, 1.0% (14/1,360) and 0.3% (3/1,017). The fetuses from 50 mg/kg-treated males did not show a significant increase in malformations, most probably reflecting a high vulnerability of PGC to the killing effect of ENU. The findings in this study suggest that germ cell stage at PGC is at risk for the induction of congenital malformations by environmental chemicals.