Effects of cytosine arabinoside on rat and rabbit embryos cultured in vitro

Abstract

The technique of rabbit whole embryo culture for 48 or 24 hr from day 9, 10 or 11 of gestation has been improved for elucidation of species differences. The effects of 1-β- d-arabinofuranosylcytosine (ara-C) and its metabolite 1-β- d-arabinofuranosyluracil (ara-U) on cultured rat and rabbit embryos were examined. Slc:SD rats on day 10.5 of gestation were explanted and cultured in rat serum containing ara-C (5–10 μg/ml) for 48 hr. Rabbit embryos of the Japanese White strain on day 9 or day 10 of gestation were explanted and cultured in rabbit serum containing ara-C (0.03–1.0 or 3–30 μg/ml) or ara-U (1.0 or 30 μg/ml) for 48 or 24 hr. Cultured rat embryos exposed to ara-C showed abnormalities of the head (malformations of the telencephalon, mesencephalon and rhombencephalon), mandible and limb bud, and short tail. Growth parameters, such as crown-rump length, head length, protein content and somite number, were reduced with increasing concentrations of ara-C. In the rabbit, embryos cultured from day 9 of gestation for 48 hr showed abnormalities of the head (telencephalon, rhombencephalon), mandible and limb bud with ara-C at 0.1 μg/ml and higher concentrations. Concentration-dependent decreases in crown-rump length, head length and protein content were observed. The findings in embryos cultured from day 10 of gestation were similar to those in embryos cultured from day 9. Ara-U produced no detectable abnormalities in embryos cultured for 48 hr from day 9 of gestation, or for 24 hr from day 10. These results indicate that ara-C has teratogenicity in vitro that is similar in both rat and rabbit embryos.