Influence of 5-azacytidine on differentiation and growth in rat nervous system tumor cell lines

In vitro studies with permanent cell lines derived from ENU-induced rat CNS and PNS tumors have shown that substances acting on second messenger systems as well as glucocorticoids have a cytostatic effect at high cell densities, but enhance proliferation at low densities. The nontoxic cytostatic effects are partially accompanied by the induction of differentiation monitored by immunocytochemistry with antibodies against GFAP, S-100 and PKC (alpha,beta). Cell differentiation with or without the influence of the drugs applied could be highly facilitated in some (CNS), but not all (PNS) types of tumor cells from neuroectodermal origin by pretreatment of cultures with 5-azacytidine under demethylating noncytostatic conditions. The implications of our results are relevant for molecular neurobiology and might offer new therapeutical approaches and may provide models for neurotoxicology.