A RAT GLIOMA MODEL, CNS-1 WITH INVASIVE CHARACTERISTICS SIMILAR TO THOSE OF HUMAN GLIOMAS - A COMPARISON TO 9L GLIOSARCOMA

A glioma cell line, CNS-1, was developed in the inbred Lewis rat to ob tain a histocompatible astrocytoma cell line with infiltrative and gro wth patterns that more closely simulate those observed in human glioma s. Rats were given weekly intravenous injections for a six month perio d with N-nitroso-N-methylurea to produce neoplasm in the central nervo us system. Intracranial tumor was isolated, enzymatically and mechanic ally digested, and placed into culture. The tumor cell line injected s ubcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 d emonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal br ain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per grou p had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was im munoreactive for glial fibrillary acidic protein, S100 protein, viment in, neural cell adhesion molecule, retinoic acid receptor a, intercell ular adhesion molecule, and neuron specific enolase. The CNS-1 cells c ommonly had one or more trisomies of chromosomes 11, 13 or 18;losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, a nd a marker chromosome made up of approximately 3 chromosomes was usua l. Comparisons of CNS-1 to 9L, gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L, and is accepted without rejecti on in non-central nervous system sites by Lewis rats.