Effects of mitomycin-C (MMC) on the incidence of neural tube defects (NTDs) and other malformations in mice with the quinky gene

This study was conducted to test the generality of Seller's results concerning the effect of MMC on NTD in curly tail mice by utilizing another mutation which produces NTD in the mouse. The effects of MMC on the incidence of NTD and other abnormalities were investigated.; Pregnant B6AF1 hybrid mice and C3H inbred mice were injected intraperitoneally with MMC once on day 8 or day 9 of gestation at a dosage of.5, 1, 2, 4, or 6 mg/kg. They were sacrificed at day 17 of pregnancy and their fetuses were examined for NTD and other malformations.; Prenatal administration of MMC increased the incidence of NTD (tail abnormalities) significantly in fetuses with the quinky gene, especially at 2, 4, and 6 mg/kg. No beneficial or curative effect on NTD was observed at any dose used on any of the two days of treatment. Mitomycin-C not only had a teratogenic effect, but it also had lethal and growth suppressing effects. Fetal mortality was significantly increased in all crosses tested. It was highest in the group treated on day 8 at 4 and 6 mg/kg. Embryos of C3H Q/+ crosses appeared to be the most severely affected by the toxic effect of MMC. As a consequence of the toxic effect of MMC, the mean litter sizes in the MMC-treated groups were significantly reduced. A growth suppression in the surviving fetuses also was recognized. However, the growth suppressing effect was more intensive when MMC was given on day 9 than day 8, especially at 2, 4, or 6 mg/kg. Mitomycin-C did induce some other abnormalities (in addition to NTD). These abnormalities included abnormal hindlimbs, abnormal eyes, umbilical hernia, multiple digital malformations (poly-, syn-, macro- and/or oligo-dactyly) and skeletal malformations, especially on the lumbosacral regions and rib abnormalities. The types of abnormalities induced with MMC treatment were the same in the three types of crosses, but the incidence varied among them.; The study may indicate that not all NTDs produced spontaneously by different mutations might be corrected or prevented by using exogenous agents such as MMC. The preventive effect might be dependent on the nature or the causation of the mutant under investigation and the time at which the defect is first initiated.