Cytotoxic effects of ethylnitrosourea on central nervous system of rat embryos. Special references to carcinogenesis and teratogenesis.

Abstract

For the purpose of observing the cytotoxic effect of N-ethyl, N-nitrosourea (ENU), a potent carcinogen on the central nervous system (CNS) at the late period of organogenesis, the embryonal telencephalic wall was hourly examined under the light and electron microscopes. Pregnant rats on the 13th day and 15th day of gestation were given either a single intravenous injection of 40 or 80 mg/kg, of ENU. The cytotoxic effect on the embryo treated on the 15th day of gestation was severer than that treated on the 13th day of gestation. The common pathological changes in both treated groups are; (1) mitotic arrest 1 hour after administration in the most inner zone of the ventricular layer, (2) degeneration and necrosis accurred predominantly in the so-called DNA synthetic zone and resulting in cell loss of the ventricular layer, (3) elimination of degenerating products; and (4) tissue repair. The findings mentioned may indicate a cytotoxic effect inducing microencephalia, and furthermore, the teratogenic and carcinogenic mechanisms are discussed.