두부 안면 형성에 미치는 Isotretinoin의 기형원적 효과에 관한 고찰

초록

Isotretinoin, newly synthesized analog of vitamin A and prescribed for severe recalcitrant cystic acne, has recently proved to be implicated in human congenital malformation. Teratogenicity of a single dose of 200 ㎎/㎏ of this compound, administered orally to pregnant ICR mice on day 7.8 or 9 of gestation, on craniofacial development were investigated. Day 8 of gestation proved to be the most sensitive period to the drug; resorption rates were 46% and 88% of the treated embryos and 100% of litters developed malformations, such as microtia, hydrocephalus, agnathia/micrognathia, microglossia, anophthalmia, malformed CNS and facial dysmorphia; treatment on day 9 affected 9 litters out of ten and 75% live fetuses mostly on their paiate and ear auricle but normal range of resorption rate, whereas none of the fetuses, treated on day 7, were affected which indicate a strong evidence of developmental stage-dependent susceptibility to the drug and stagespecific pattern of malformation. The susceptibility to the drug on day 9 is more selective and limited, that is, 75% of fetuses treated on day 8 had multiple anomalies and 18% had a single, while the ratio was reversed on day 9. Skeletal defect/or hypogenesis usually coincided with those seen in external or section findings and defect of ear ossicles and tympanic ring usually associated with microtia. The results indicate that the malformation produced in human with fetal exposure to the drug can be induced in mice and in seems that the target of the drug at these stage of development might be neural crest and developing neuroepithelium.