Phenytoin is clinically used as an anti-epilepsy drug and also is known as an inducer of cleft palate in the craniofacial area. It may be suggested that phenytoin cause cleft palate through the glucocorticoid receptor in the same fashion as does steroid hormone in mouse embryonic palates.

In order to investigate the teratogenic mechanism of phenytoin on the cleft palate, the present study examined immunohistochemically with anti-glucocorticoid receptor antigen and the incorporation of ³H-thymidine into the embryonic palate in which phenytoin (75㎎/㎏) had been intraperitoneally injected twice:on the day 12th and 13th of pregnancy of ddY mice.

The results obtained are as follows: In the control group, palatine shelves were fused on the 14th day of pregnancy. On the other hand, in most of the phenytoin-treated animals, palatine shelves were fused on the 15 day pregnancy one day later than the control group. At this stage, the failure of the adhesion of the palatine shelves caused the cleft palate. Intense immunostaining of anti-glucocorticoid receptor was observed on the cleft palates of phenytoin-treated group. Also, incorporation of ³H-thymidine was completely inhibited in the cleft palates of the phenytoin-treated group. These results indicate that phenytoin can induce the cleft palates by inhibition of DNA synthesis initiated via glucocorticoid receptor.