[Initial cellular damage in the developing rat brain caused by cytotoxicity of ethylnitrosourea]

Initial cellular degeneration in developing rat fetal brains were induced during the early cytogenetic period of neuroblasts by cytotoxic action of ethylnitrosourea (ENU). This was transplacentally administered. After a single intravenous administration of 60 mg/kg body weight ENU to 16th day-pregnant rats, each fetus was removed surgically from the uteri every hour for 24 hours and every day for 9 days. These were fixed by the transcardial perfusion method to observe them with light and electron microscopes. From 4 hours after the ENU-treatment, the degenerative alteration of cells, characterized ultrastructurally by cytoplasmic condensation and nuclear pyknosis, developed selectively in the matrix cell layer of the fetal cerebrum where active cell division was carried out to produce neuroblasts. Cellular degeneration was first noticed at the zone of DNA synthesis and then all the matrix cell layer including the mitotic phase. Furthermore, the cell processes of matrix cells, or so-called radical fibers, were also recognized to be in the same degenerative processes. These affected cells increased in number and became arranged in columns along the radial fibers through the process of time, and successively migrated to the migrating zone through the outer part of the matrix cell layer. At 10 hours after treatment, many cells were observed in the migrating zone and a few cells were noticed in the matrix cell layer. The degenerated neuroblasts reached the cortical plate about 3 hours after the development of initial degeneration. In contrast, the neuroblasts in the cerebral cortical plate which had already been formed at the time of ENU administration were not affected by the ENU and persisted for the following developments.(ABSTRACT TRUNCATED AT 250 WORDS)