Abnormal development of mouse embryos exposed to methylnitrosourea before implantation

On day 2 of gestation mice were exposed to single i.p. injections of 5, 10, 20, and 40 mg/kg methylnitrosourea (MNU). Evaluation at term revealed 100% embryolethality in the 40 mg/kg group but no signs of maternal toxicity (LD50 = 400 mg/kg). In mice treated with 5 and 10 mg/kg, no malformations could be detected at term. In contrast, 40% of the live fetuses exposed to 20 mg/kg MNU showed developmental abnormalities of vertebrae, ribs, long bones, and kidneys. Analysis of postnatal development 3 weeks after birth indicated a significant increase in mortality in the offspring of all animals exposed to MNU on day 2 of pregnancy. Further developmental or morphologic anomalies could not be detected in the offspring up to the age of 6 months, when autopsy was performed. The data show that exposure to MNU before implantation has embryolethal and teratogenic effects in a dose range one order of magnitude lower than the toxic dose range for adult animals.