The effects of disulfiram on the experimental C3H mouse embryo

Disulfiram, in 1 mg and 10 mg oral doses, was given to inbred C3H mice prior to and for the duration of pregnancy. The effects on the fetus have been assessed at 18 days gestation by means of fetal and placental weights, number of resorptions, skeletal preparations and Wilson's sections. Disulfiram dissolved in diethyl ether was administered to 8- and 9-day embryos in vitro in concentrations of 0.1, 10 and 100 micrograms ml-1 of culture medium, and the effects of ether alone and ether plus disulfiram assessed by evaluation of morphological development over a 28-h period, and inhibition of DNA synthesis using tritiated thymidine labelling over a 4-h period. Disulfiram (1 mg) in vivo caused no adverse effects on the fetus, but disulfiram (10 mg) was toxic, in that it caused a significant increase in early resorptions. Disulfiram in vitro, in the 10 and 100 micrograms ml-1 concentrations, proved to be very toxic to the embryos, affecting both morphological development and DNA synthesis in 9-day embryos and morphological development in 8-day embryos. DNA synthesis was only inhibited at the 100 micrograms ml-1 concentration in 8-day embryos. The 0.1 micrograms ml-1 concentration of disulfiram caused abnormal central nervous system development in 8-day embryos, but was otherwise non-toxic to 8- and 9-day embryos. Apart from a reduction in somite counts, ether in concentrations of 0.285 mg ml-1 and 2.85 mg ml-1 caused no adverse effects on morphological development in 8- or 9-day embryos. DNA synthesis was inhibited by ether in a concentration of 2.85 mg ml-1 in 9-day embryos.