Research and Development Studies Relative to the Experimental Induction of Oral Facial Malformations in the Rhesus Monkey ('Macaca mulatta')

摘要

A total of 140 timed-pregnant rhesus monkeys were treated during early gestation with either BAPN (4 animals), Dilantin (7), Thalidomide or E-122 (4), Cytoxan (116), Bendectin (5), or pyridoxine (4). Although the number of treated animals was too small for definitive conclusions, developmental anomalies were not detected in offspring of animals treated with BAPN, Dilantin, Bendectin or pyridoxine. In contrast, Cytoxan treatment during early gestation resulted in a high incidence of malformations in the offspring. These malformations varied, depending on the time of treatment, but consisted primarily of either cleft palate and/or cleft lip or craniofacial dysmorphia with either meningoencephalocele or persistent anterior fontanel. Nursery-raised infants that were prenatally exposed to Cytoxan showed a high mortality rate, and at autopsy, often showed severe thymic hypoplasia, suggestive of an induced immuno-deficiency. The frequency and reproducibility of the Cytoxan-induced anomalies suggest that infants treated in this manner could be developed as animal models for these relatively common human disorders.