A Comparison of the In Vivo and In Vitro Response of Rat Embryos to 5-Fluorouracil.

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  • KUWAGATA Makiko
    Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center
  • TAKASHIMA Hiromasa
    Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center
  • NAGAO Tetsuji
    Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center

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  • comparison of the in vivo and in vitro

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Abstract

This study serves to further define the capabilities of the whole embryo culture system using the well-known teratogen, 5-fluorouracil (5-FU), an antineoplastic agent. An initial in vivo study was performed whereby 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 number 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 treated groups. An in vitro study was performed in which drug concentrations were varied (0.15-0.30 μg/ml). Externally abnormal embryos were observed in whole embryo culture system from embryonic day 9 to 11. The most common defect was hypoplastic optic vesicles. In the whole embryo culture system, crown-rump length, somite number, protein contents, and morphological score were decreased in a dose-dependent fashion. Finally, histological evaluation and observation of the pattern of cell death of the optic vesicle of 11-day-old embryos in in vivo and in vitro were performed. These parameters revealed no differences in response between in vivo and in vitro embryos treated with 5-FU, suggesting that the whole embryo culture system was an appropriate model for developmental toxicity studies of 5-FU.

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