Teratogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine in mice

The teratogenic effect on the mouse fetus of a potently mutagenic and carcinogenic agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was studied. Pregnant mice were injected on one of gestation days 7-12 with an intraperitoneal dose of 40, 60 or 80 mg/kg of MNNG, and fetuses were examined on day 18 of gestation. Various malformations affecting the brain, face, vertebra, rib and limb appeared in high frequency. Brain malformations were the most predominant; hydrocephalus, hydromicrocephaly and microcephaly appeared in sequence with developmental stages of treatment, although exencephaly occurred infrequently. Cleft palate, sometimes associated with microglossia and micrognathia, and vertebral anomalies including tail defect were observed following almost every gestation-day treatment. Long-bone defects of fore- and hindlimbs were also predominant. Polydactyly, ectrodactyly and microdactyly frequently occurred together in the fore- or hindlimbs or both in sequence with treatment stages. Ectrodactyly and microdactyly appeared with greater frequency on the left than on the right in both fore- and hindlimbs, but polydactyly and long-bone defects appeared bilaterally.