Teratogenetic Study of Vincristine

In order to elucidate the relationship of facial anomalies and cerebral anomalies, especially to holoprosencephaly, a single isoraperitoneal injection of 0.2mg/kg vincristine was performed in rats during the period from 7th to 14th day of gestation. Fetuses were extracted on the 21st day of gestation for observation, with the result described as follows:<BR>In the vincristine-treated groups, from 9th day and 6 hours to 10th day and 0 hour of gestation, all embryos and fetuses were dead. The mortality of fetus in the treated groups during the period from 8th and 6hours to 9th day and 0 hour of gestation was 28.2%, while various congenital anomalies were observed in 61.4% of survived fetuses in these groups. The mortality of fetus during periods except for those mentioned above was extremely low and no anomaly was observed in survived fetuses.<BR>Congenital anomalies were observed in this experiment mainly consisted of cerebral an omalies such as acephalia, pseudencephalia or encephalocele, microcephalia or trigonocephalia and facial anomalies such as mandibular hypoplasia, naso-maxillary hypoplasia, cleft lip and alveolous, low position of the ear, anophthalmia and microphthalmia. The incidence of anomaly in other regions of the body was extremely low. Among these anomalies, cerebral anomalies were most commonly observed followed by anomalies of the eye, mandiblar hypoplasia, cleft lip and alveolous, low position of the ear and naso-maxillary hypoplasia in this order.<BR>As for cleft lip and alveolous, unilateral cleft wa s predominant, that followed by median clefo lip, but bilateral cleft was less encountered. As combined anomalies with cleft lip and alveopous, anomalies of the eye, pseudencephalia or encephalocele were most frequently observed and followed by microcephalia or trignocephalia. The incidence of combined anomalies was most frequently observed in unilateral cleft and next in median cleft. The incidence of that was more common in incomplete cleft than in complete cleft. However, the incidence of combined anomalies with complete median cleft was highest. Low position of the ear was noted in 68.2% of fetuses with mandibular hypoplasia, while 40.0% of fetuses with mandibular hypoplasia simultaneously showed low position of the ear, microcephalia or trigonocephalia. As combined anomalies with mandibular hypoplasia, cerebral anomalies were most common, followed by anomalies of the eye.<BR>The differentiation of telencephalon in holoprosencephaly was not observed in s ome but slighty observed in others. No differentiation and incomplete development of arhinencephalia were observed in holoprosencephaly. Such holoprosencephaly were frequently observed in microcephalia or trigonocephalia, and otocephalia. The eye tissues with some incomplete development markedly closed as compared to those in normal fetuses. Fetuses with otocephalia simultaneously showing low position of the ear and mandibular aplasia or hypoplasia had incompletey developed rhinencephalon in general.