Drug-induced Craniofacial Malformations in Newborn Rats -Investigation of its Pathohistogenesis and Apoptosis -

为探讨长春新碱、长春新碱和维生素A的致畸作用，对妊娠7~13天的Wistar大鼠进行了腹腔注射，并于第21天取出胎儿进行检查。长春新碱组第10天0.25 mg/kg和维生素A组第8天150 IU/kg的活体腭裂发生率分别为9.1%和9.1%。长春花碱治疗组未见颅面异常，各组均未发现肢体和躯干畸形。肢体、躯干药物畸形增多。为了检测上述过程所致的产前腭裂融合期细胞凋亡的情况，对各用药组进行了Fas和Fas配体(TUNEL和单链DNA)的检索。而在尸检当天组织学认为是细胞凋亡表达的腭裂融合区，未见Fas和Fas配体阳性细胞。这很可能是其有限的和更早的细胞凋亡时间的原因。

To investigate the tetrogenic effect of vincristine, vinblastine and vitamin A, intraperitoneal injection of these drugs was performed into the pregnant Wistar rats on the 7^<th> to 13^<th> days of gestation and fetuses were extracted on the 21^<st> day for examination. The incidence of cleft palate in vivo was 9.1% in a vincristine-treated group at a dose of 0.25mg/kg on 10^<th> day and vitamin A-treated group at a dose of 150 IU/kg on 8^<th> day. In a vinblastine-treated group, any craniofacial anomaly did not occur and in all groups, no malformation of extremities and trunk were found. And increasing of drug malformation of extremities and trunk were found. And increasing of drug dosage seemed to relate the fetal mortality rate.To examine the appearance of apoptosis at the prenatal palatal fusion stage that induced above procedure, Fas ad Fas ligand were searched (TUNEL and single stranded DNA) in each drug group. But no Fas and Fas ligand positive cell were marked at the palatal fusion area that histologically considered to be an expression of apoptosis on the day of autopsy. It most probably causes of its limited and earlier timing of an apoptosis.