Effects of ascorbic acid on the mouse embryo and on cyclophosphamide-induced cephalic DNA strand breaks in vivo

Abstract

Pregnant C₃H mice were exposed to 3.34 and 6.68 g ascorbic acid/kg body weight on the 11th day postcopulation, and to co-administration of a teratogenic dose of cyclophosphamide (CP, 15 mg/kg body weight). The effects on embryonal cephalic DNA strand breaks were assessed 16 h after drug administration. In order to establish whether vitamin C was embryotoxic or altered CP-induced toxicity, mice were sacrificed on day 18 after copulation to record fetal weights, gross morphological abnormalities, and fetal mortality. Administration of 3.34 g ascorbate/kg was not associated with demonstrable toxic effects but with 6.68 g ascorbic acid/kg there was a 46% incidence of fetal mortality. In embryos exposed to CP, 15 mg/kg, there was a decrease in fetal weight (median fetal weight 678 mg compared with 967 mg in controls), all fetuses were morphologically abnormal and 59% of cephalic DNA was double stranded compared with 81% for controls (p<0.001). When vitamin C, 3.34 g/kg, was co-administered with CP the incidence of DNA strand breaks remained unchanged. However, all fetuses were morphologically normal and there was no reduction in fetal weight. These findings demonstrate that administration of 6.68 g vitamin C/kg is toxic to the mouse embryo, but a lower dose of 3.34 g/kg is not, and has a protective effect against the toxic manifestations of CP. This protection is not associated with prevention of cephalic DNA strand breaks.