Morphological maturation of tumor cells induced by ethylnitrosourea (ENU) in rat brains. I. On the tumors by administration of ENU in the late gestational stage

Abstract

Sequential changes in the development of ethylnitrosourea (ENU)-induced rat brain tumors were examined histologically, immunohistochemically, electron microscopically and autoradiographically. In 47 Sprague-Dawley rats transplacentally administered ENU, 95 brain tumors developed, including 76 microtumors less than 1mm in diameter. Microtumors were found mainly in the paraventricular area, but some were found in the peripheral brain tissue. They were composed of small tumor cells which had round dark nuclei and scanty cytoplasm immunohistochemically negative for Leu 7 and glial fibrillary acidic protein (GFAP). The 19 macrotumors were mature gliomas, 3 of which histologically corresponded to oligodendrogliomas and 16 to mixed gliomas. The tumor cells of the former had small round nuclei with distinct perinuclear halos and a small amount of cytoplasm positive for Leu 7. The latter were chiefly composed of polygonal cells having large round nuclei and rich cytoplasm positive for GFAP. An autoradiographic study using 3H-thymidine revealed that the labeling index of the tumor cells was high in mixed gliomas and microtumors, but low in oligodendrogliomas. It may be concluded that the constituent cells of microtumors correspond to glioblasts or migrating neuroglias, which gradually mature to form oligodendrogliomas or astrocytomas.