EFFECTS OF ANTICONVULSANT DRUGS ON FETAL MOUSE PALATES CULTURED IN-VITRO

Maxillary regions of day-12.5 ICR mouse fetuses were dissected and cul tured in a chemically defined serumless medium, and the effects of ant iconvulsant drugs on in vitro palatogenesis were studied. The explants were treated for 72 h in vitro with 50 to 200 mug/mL diphenylhydantoi n (DPH), 200 to 800 mug/mL sodium phenobarbital (PB), 12.5 to 400 mug/ mL sodium valproate (VPA), and 3 to 100 mug/mL diazepam (DAZ). During the culture, the secondary palatal shelves of control explants elevate d, grew medially, and fused after 72-h culture in a manner similar to the palatogenetic process in vivo. The fusion of palatal shelves was i nhibited dose-dependently by treatments with DPH, VPA, and DAZ. PB sho wed no significant inhibitory effects on palatal fusion at concentrati ons up to 800 mug/mL. The in vitro toxicity of the anticonvulsants tes ted appeared to correlate with the relative in vivo teratogenic potent ial of the drugs. The present study demonstrated that the in vitro org an culture system should be useful for screening teratogenic agents, e specially those causing cleft palate, and for exploring the mechanisms of cleft palate formation.