Effects of prenatal administration of hadacidin, a cancer chemotherapeutic agent, on the development of hamster fetuses

Abstract

A single intraperitoneal injection of 1-2-5 g/kg body weight of hadacidin was teratogenic when administered to pregnant hamsters between days 8 and 11 of gestation. Both the frequency of malformation and resorption were related to the dose and time of hadacidin administration. The drug produced both gross and microscopic malformation in the fetus and impaired its general growth. The malformation involved craniofacial structures, central nervous system, respiratory, digestive and urinary systems, limbs and tail. Morphologically different types of cleft lip and cleft palate were related to the dose and time of hadacidin treatment. An association was observed between cleft lip, cleft palate and micrognathia on one hand, and between cleft palate and micrognathia on the other. Significance of association between the lip, the palate and the mandibular malformation was discussed and the hypothesis that human cases of Pierre Robin syndrome may result from an environmental assault was supported. It was suggested that the fetal weight and the microscopic analysis should be included in the criteria for the teratological drug safety evaluation procedures.