The development of experimental brain tumours a sequential light and electron microscope study of the subependymal...

Pregnant BD-IX rats were given a single intraperitoneal injection of 30 mg of N-ethyl-N-nitrosourea (ENU) per kg of body weight on the 15th day of gestation. The offspring were killed at fortnightly intervals between 2 and 20 weeks of age. The subependymal plate region adjacent to the lateral ventricles was examined by light and electron microscopy to study the early stages in the development of brain tumours. Microtumours, composed of subependymal plate cells, glioblasts and various glial cells at different stages of maturation, were found in 16-, 18-, and 20-week-old rats. The most common site for microtumours was the angle of the lateral ventricles between the corpus callosum and caudate nucleus; others were located at the lateral aspect of the ventricles. It is suggested that most, if not all, cerebral gliomas originate from the undifferentiated cells of the subependymal plate: these mitotically active stem cells provide a susceptible target for the carcinogenic stimulus. The morphology of the gliomas developed is determined by the diverging processes of differentiation and anaplasia resulting in a pleomorphic cell population. The relevance of this experimental model to the pathogenesis of human gliomas is discussed.