DEVELOPMENTAL ABNORMALITIES OF SKELETAL SYSTEM INDUCED BY ETHYLURETHAN IN THE RAT

Abstract

Since the incidence of congenital malformations caused by thalidomide in humans, a number of teratogenic studies on the compound has been reported in a variety of experimental animals. However, great variation in the susceptibility has been presented in different species and strains. Basil et al. (1) and Faigle et al. (2) have shown that the metabolite of thalidomide responsible for the teratogenicity is probably its hydrolytic product of the peptide bonds present in the molecule and that the metabolite interferes with incorporation of glutamine or glutamic acid into the cell constituents. There are some other possible mechanisms of thalidomide for the teratogenicity (3). For instance, it has been reported that hydroxyurea reduces the rate of incorporation of thymidine into Ehrlich ascites tumor cells and inhibits the cell division through interference with DNA metabolism (4). Ethylurethan has been used in the treatment of neoplastic disease probably due to inhibition of nucleoprotein synthesis (5). However, the exact mechanism of the cytotoxic action of ethylurethan remains to be settled. Its chemical structure is partially related to that of teratogens such as thalidomide, azaserine (6) and DON (6-diazo-5-oxoL-norleucine) (7). The congenital malformations in mouse embryos induced by ethylurethan have been described by Sinclair (8), Kanamori (9) and Nishimura and Kuginuki (10). Hall (11) has demonstrated the developmental anomalies in the eye of the rat caused by ethylurethan. The preventing effects of thyroxine and vitamins on the teratogenicity of ethylurethan have been reported in mice (12). The species difference in the teratogenicity of the compound is not known exactly. The preset experiment is the first attempt in a series of studies on the tetratogenic mechanism of carbamate derivatives, and deals with the tetratogenic effects of ethylurethan on the rat embryos.