Effects of caffeine and related methylxanthines on fetal mouse palates cultured in vitro.
The maxillary regions of day-12.5 ICR mouse fetuses were cultured in a chemically-defined serumless medium and the effects of methylxanthine derivatives on cultured palates were studied. Explanted palates were treated for 72 hr in vitro with 0.5-2 mM caffeine (CA), 1-2 mM theophylline (TP), or 1-2 mM theobromine (TB). Although the three compounds tested did not prevent the contact of opposing palatal shelves, palatal fusion was inhibited by CA and TP at a concentration of 2 mM, and the inhibitory effect of CA was more evident than that of TP. On the other hand, TB did not exert an inhibitory effect on palatogenesis at 2 mM. Since the in vitro toxicity of the methylxanthine compounds appeared to correlate well with their in vivo teratogenic potential, the organ culture method of fetal rodent palates should be a useful tool for screening teratogenic agents, especially those causing cleft palate.
Kosazuma
T
T
Institute of Applied Medicine, Hokkaido Radio-isotope Center, Ltd., Japan.
Kawauchi
S
S
D000818:Animals; D002110:Caffeine / Q000633:toxicity*; D016009:Chi-Square Distribution; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D010159:Palate / Q000187:drug effects* / Q000196:embryology; D013805:Theobromine / Q000633:toxicity; D013806:Theophylline / Q000633:toxicity; D014970:Xanthines / Q000633:toxicity*
D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D013806:Theophylline; D013805:Theobromine