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Brain tumors were induced in 3-month-old rabbits of either sex by repeated intravenous injections of N-methyl-N-nitrosourea. Twelve brain tumors (6 pleomorphic gliomas, 5 grade 2--3 astrocytomas, 1 grade 2--3 oligodendroglioma) were established in culture and, with the exception of 2 neoplasms, were propagated in vitro as permanent cell lines. The glial nature of all cell lines was ascertained at several passage levels by testing the cells for the production of S-100 and GFA. It could be shown that most cells of all lines fluoresced positively for the S-100 protein, albeit differences in intensity of fluorescence were clearly noted between cells of the same culture and between different cultures. In general, astrocytoma cell lines had the strongest fluorescence. Pleomorphic glioma cells but especially astrocytoma cells reacted positively also for the GFA protein. Surprisingly enough, isolated cells of the oligodendroglioma line also showed evidence of GFA production. Exposure of cultures of rabbit glioma cells to db-cAMP for 8--10 hr resulted in inhibition of cell proliferation and stimulation of process formation. Furthermore, positive fluorescence for the S-100 and GFA proteins was more intense in cells treated with db-cAMP than in untreated cells. The latter observation may indicate that production and/or accumulation of glial proteins also was enhanced during the stationary phase of cell cultures.

Four mixed oligodendrogliomas and astrocytomas were investigated by electron microscopy and immunohistochemistry (GFAP, NSE and MBP). GFAP-positive oligodendroglioma cells and their transitional cells to GFAP-negative oligodendroglioma cells were present, suggesting successive morphological changes of astrocytic tumor cells. NSE-positive cells, suggestive of residual neurons, also exhibited round nuclei and perinuclear halos. On electron microscopy, oligodendroglioma cells that showed glial filaments, vascular end-feet and zonulae adherentes were occasionally present. The tumor cells with or without astrocytic characteristics showed common features of cytoplasmic organelles. These findings suggest that most oligodendroglioma cells in mixed gliomas are of an astrocytic nature and that characteristic microscopic features of oligodendroglioma are of a common cellular form that can be taken by various types of cells under certain circumstances.