The cytotoxic effect of ethylnitrosourea on the developing rat cerebellum. Morphologic observations

A single i.p. injection of 240 mg/kg of ethylnitrosourea (ENU) into rats in the perinatal period resulted in lethal damage to the proliferating external granular cells of the developing cerebellar cortex. Lethally damaged cells of the external granular layer were also observed in fetal rats at 20 days of gestation after transplacental administration of the same dose of ENU. The percentage of susceptible cells affected remained constant throughout the period investigated. Light microscopy showed large numbers of randomly distributed pyknotic nuclei and complete inhibition of mitotic activity 6 h after ENU administration. Electron-microscopic examination showed that damaged granular cells had clumping of chromatin along the nuclear membrane. Cell organelles were morphologically distorted and unidentifiable; lysosomal bodies accumulated in the cytoplasm. Nonproliferating Purkinje cells were not lethally affected; however, dilatation of the Golgi apparatus and an increase in the number of lysosomes were commonly observed cytoplasmic changes.