Morphological and immunohistochemical evidence for the presence of subcortical target cells of N-ethyl-N-nitrosourea-induced cerebellar tumors in rats.

Morphological and immunohistochemical studies of cerebellar tumor induction with neonatal administration of N-ethyl-N-nitrosourea (ENU) were conducted in four strains of rats and their hybrids, i.e., noninbred Wistar, Fischer (F344), Long-Evans, Wistar/Furth, and hybrids of Long-Evans and Wistar/Furth. Neonatal s.c. injection of 40 mg ENU/kg body weight produced 53 cerebellar tumors in 46 (8.4%) rats among 550 animals. There was no sex difference in the incidence (male = 9.6%; female = 7.0%). Histological examination showed that most of the tumors (83%) were oligodendrogliomas and the neoplastic cells were positively stained immunohistochemically with anti-Leu-7 monoclonal antibody. In examining the location of cerebellar tumors, 22 (42%) were located in the vermis, 11 (21%) in the hemisphere, 9 (17%) in the flocculus, 6 (11%) in the peduncle, and 5 (9%) in other sites. When their origins were examined in relation to their location to the internal granular layer of the cerebellum, 40 (75%) tumors were found just under the internal granular layer (subcortical region) and 9 (17%) in the white matter or cerebellar nuclei. Only 2 (4%) subependymal tumors were observed. Ontogenic study of the rat cerebellum revealed the presence of an aggregation of primitive glial cells in the subcortical region during the neonatal period, and the [3H]thymidine pulse-labeling index of these cells was 13.7%. Electron microscopic study showed the primitive nature of these cells and they reacted positively with anti-Leu-7 monoclonal antibody. These results indicate that cerebellar tumors are induced in an appreciable incidence with neonatal injection of ENU in rats and that cerebellar target cells in the subcortical region are present after ENU carcinogenesis.