Effects of L-2-oxothiazolidine-4-carboxylate, a Cysteine Pro-drug, on Teratogenicity of 5-fluorouracil in Mice

Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by L-2-oxothiazolidine-4-carboxylate (OTC), a cysteine pro-drug, were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 950 mg/kg of OTC 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with OTC decreased the frequency and severity of oligodactyly induced by 5-FU, although the differences were not significant statistically. There was little difference in either liver glutathione levels, or body weight gain during gestation of dams between the 5-FU group and the 5-FU plus OTC group. Fetal mortality and fetal weight of the group treated with 5-FU alone were comparable with those of the group pretreated with OTC. In the present study, teratogenicity of 5-FU seemed to be slightly mitigated with OTC pretreatment.