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Susceptibility of Day‐12.5 and Day‐13.5 Fetal Mouse Palates Cultured in Vitro to 5‐Fluorouracil and Hydroxyurea
Author(s) -
KOSAZUMA Tsuneo,
KAWAUCHI Saju,
CHOU MingJen,
SHIOTA Kohei
Publication year - 1994
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1994.tb00601.x
Subject(s) - fetus , biology , in vitro , andrology , teratology , medicine , pregnancy , biochemistry , genetics
The maxillary regions of day‐12.5 and day‐13.5 ICR mouse fetuses were cultivated in a chemically‐defined serumless medium by a suspension culture technique to examine the toxic effects of 5‐fluorouracil (5‐FU) and hydroxyurea (HU) on cultured palates and to compare the sensitivity of fetal mouse palates at different stages of development. The palates of day‐12.5 and day‐13.5 fetal mice were explanted and exposed in vitro for 72 hr to 0.1–50 μg 5‐FU/ml or to 5–76 μg HU/ml. 5‐FU inhibited the growth and fusion of day‐12.5 palatal shelves in vitro dependently on its concentrations. Day‐13.5 palates were significantly less sensitive to 5‐FU than day‐12.5 palates, and the minimal toxic concentrations (MTCs) of 5‐FU were 0.1 and 10 μg/ml for day‐12.5 and day‐13.5 fetal palates, respectively. HU inhibited the in vitro growth and fusion of day‐12.5 fetal palatal shelves in a concentration dependent manner, but only slightly suppressed the growth of day‐13.5 fetal palates. The MTCs of HU were 19 and 76 μg/ml for day‐12.5 and day‐13.5 fetal palates, respectively. Therefore, day‐12.5 fetal mouse palates (at stage‐1 or earlier stages of palatogenesis) seemed significantly more susceptible to these teratogenic chemicals than day‐13.5 fetal palates (at stages 2–3 of palatogenesis). The palates of day‐12.5 ICR fetal mice may be more suitable than day‐13.5 palates for in vitro teratogen screening and for the study of mechanisms of normal and abnormal palatogenesis.