A COMPARISON OF THE IN-VIVO AND IN-VITRO RESPONSE OF RAT EMBRYOS TO 5-FLUOROURACIL

This study serves to further define the capabilities of the whole embr yo culture system using the well-known teratogen, 5-fluorouracil (5-FU ), an antineoplastic agent. An initial in vivo study was performed whe reby pregnant rats were injected intraperitoneally with 10-30 mg/kg 5- FU on day 9 of gestation. On day 20 of gestation, the effects of this drug on the growth and development of embryos were evaluated. The numb er of externally malformed fetuses increased in a dose-related manner, and the most common defect was micro-/anophthalmos in fetuses of dams treated with 5-FU. Growth retardation was also noted in the 5-FU trea ted groups. An in vitro study was performed in which drug concentratio ns were varied (0.15-0.30 mu g/ml). Externally abnormal embryos were o bserved in whole embryo culture system from embryonic day 9 to 11. The most common defect was hypoplastic optic vesicles. ln the whole embry o culture system, crown-rump length, somite number, protein contents, and morphological score were decreased in a dose-dependent fashion. Fi nally, histological evaluation and observation of the pattern of cell death of the optic vesicle of ii-day-old embryos in in vivo and in vit ro were performed. These parameters revealed no differences in respons e between in vivo and in vitro embryos treated with 5-FU, suggesting t hat the whole embryo culture system was an appropriate model for devel opmental toxicity studies of 5-FU.