CHANGES IN SURFACE MORPHOLOGY ASSOCIATED WITH ETHYLNITROSOUREA-INDUCED MALIGNANT TRANSFORMATION OF CULTURED RAT-BRAIN CELLS STUDIED BY SCANNING ELECTRON-MICROSCOPY

Abstract

Cultures of cells clonally derived from either normal adult rat brain or a culture of a mixed glioma induced by ethylnitrosourea (ENU) were studied by scanning electron microscopy [SEM]. The 2 control lines, ARBOC9 and ARBOC11, displayed very little surface activity. The cells were large, extremely flat with prominent nuclei and had few microvilli or ruffles. The 2 tumor lines A15A5 and A15A10 displayed a striking amount of surface activity which greatly exceeded that shown by the control cells grown and fixed under identical conditions. These cells were highly condensed and possessed large numbers of blebs, filopodia and microvilli. Cells derived from rat brains transplacentally exposed to either ENU or citrate buffer and cultured at 111-112 days after injection (when no tumor was visible) were also studied. Some of the cultures derived from ENU-exposed animals during the latent period were tumorigenic showing that malignant cells were already present. These cultures in general displayed features found in the tumor clones while control cultures did not. One line of cells exposed to ENU which did not yet show transformed properties such as growth in agar, tumorigenicity or high fibrinolytic activity displayed an intermediate morphology between control and tumorigenic lines. It subsequently became transformed and then displayed high surface activity.