Isotretinoin 투여로 인한 구개열 발생과정에 관한 실험적 연구

초록

Isotretinoin (retinoic acid-13 cis,®Accutane), an analog of vitamin A and prescribed for severe recalcitrant cystic acne, has recently proved to be a horrible teratogen in human inducing congenital malformation in organs chiefly derived from ectomesenchyme. The status and morphology of the palatal shelves with changes of carbohydrate containing cell surface macromolecules during the process of isotretinoin-induced cleft palate in DDY mice, following administration of single oral dose of 150㎎/㎏ of isotretinoin (RO4-3780, Hoffmann LaRoche), were investigated. The compound caused fetal death around 24 hours after treatment and produced cleft palate at about 43% of live fetuses and the drug delayed the palatogenetic movement/process especially that of shelf elevation with temporal inhibition of increment of palatal mesenchymal cell density that occurs as a normal process from just prior to shelf elevation till fusion. In addition, the drug prevented shelf medial epithelia from their degenerative change which is one of normal developmental phenomena as selective cell death but did not have much influence on PAS and PAPS reaction both in epithelia and mesenchyme. With the results it seems that isotretinoin-induced cleft palate results from a combination of suppressive effects of the compound on proliferation of palatal mesenchymal cells with consequent delay in palatogenetic movement and inhibitory of effects on epithelial selective ceil death with consequent interference of shelf fusion.