The effect of 5-fluorouracil on [ 3H]nucleoside incorporation into the DNA of mouse embryos and maternal tissues

Abstract

Pregnant albino mice (ICR) were administered, ip, 40 mg/kg 5-fluorouracil (5-FU) on Day 10 of gestation. This dosage produced 96.3% embryolethality and 100% of the surviving fetuses were malformed. This dosage also produced a pronounced inhibition of 6-[ 3H]dUrd incorporation into the DNA of the embryo, chorioallantoic placenta, maternal intestine, and maternal spleen. There was no recovery in the embryo or placenta over the 48 hr time period analyzed. In the maternal tissues, however, incorporation levels returned to control values by 48 hr after 5-FU administration. 5-FU had no effect on 6-[ 3H]dThd incorporation into the DNA of any of the mitotically active tissues with the exception of the embryo at the 48 hr time point. Concomitant histological studies of the embryo neural tube showed that 40 mg/kg 5-FU produced mitotic inhibition 2 hr after treatment. Cell death began at 4 hr with heteropycnosis in the DNA synthetic zone of the primitive ependymal layer. As with the incorporation experiment, there was no histological recovery in the neural epithelium and the pycnosis became progressively more severe with time after 5-FU treatment.