The effect of administration time on malformations induced by three anticonvulsant agents in C57BL/6J mice with emphasis on forelimb ectrodactyly.
Exposure of C57BL/6J mice to three anticonvulsant derivatives, namely, dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly. The agents were administered at gestational days 9, 9 1/3, 9 2/3, and 10. It was determined that administration at day 9 2/3 induced the highest percentage of forelimb ectrodactyly for each of the three agents. The forelimb ectrodactyly response in the C57BL/6J strain was compared with the A/J strain (Collins et al., Teratology, 41:61-70, 1990); it was found that the C57BL/6J strain was more sensitive to dimethadione and the A/J strain was more sensitive to diphenylhydantoin and sodium valproate. The position of vertebral defects induced by sodium valproate correlated with the time of drug administration. The overall syndrome of malformations induced by the three anticonvulsant agents was relatively similar in the two mouse strains and differed between each of the anticonvulsant agents.
Collins
M D
MD
Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Ohio 45229.
Walling
K M
KM
Resnick
E
E
Scott
W J
WJ
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000853:Anophthalmos / Q000139:chemically induced; D000927:Anticonvulsants / Q000633:toxicity*; D004114:Dimethadione / Q000633:toxicity; D005147:Facial Bones / Q000002:abnormalities; D005260:Female; D005552:Forelimb / Q000002:abnormalities*; D005865:Gestational Age; D007668:Kidney / Q000002:abnormalities; D008428:Maternal Mortality; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D008850:Microphthalmos / Q000139:chemically induced; D010672:Phenytoin / Q000633:toxicity; D011247:Pregnancy; D012886:Skull / Q000002:abnormalities; D013131:Spine / Q000002:abnormalities; D014635:Valproic Acid / Q000633:toxicity
D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin; D004114:Dimethadione