GANGLIOSIDES HAVE A BIMODAL EFFECT ON DNA-SYNTHESIS IN U-1242 MG HUMAN GLIOMA-CELLS

GM1, GD1a, and GT1b inhibit both PDGF-stimulated and serum-stimulated DNA synthesis in Swiss 3T3 cells and the human glioma cell line U-1242 MG in a dose-dependent manner, The ganglioside inhibitory effect is c ounteracted in a dose-responsive fashion by serum such that gangliosid e-induced inhibition is essentially abolished in 10% serum, Because of the potentially important role that gangliosides play in growth regul ation of human gliomas, this phenomenon was studied in detail using U- 1242 MG cells, Stimulation of DNA synthesis by low doses of serum in U -1242 MG cells is inhibited in a dose-responsive fashion by gangliosid e GM1. However, serum itself counteracts the inhibitory effect of gang lioside in a dose responsive way, Kinetic analyses demonstrate that GM 1 competes with some components of serum for sites on U-1242 MG cells (Kb of GM1 = 12.5 mu M). On the other hand, GM1, GD1a, and GT1b stimul ate DNA synthesis in quiescent U-1242 MG cells in both sparse and conf luent conditions, indicating that ganglioside-stimulated DNA synthesis is dependent on the phase of cellular growth rather than cellular den sity. This growth stimulatory effect of gangliosides is more potent on quiescent, confluent cells than quiescent, sparse cells, These result s demonstrate that exogenously added gangliosides can have opposite (b imodal) effects on progression of human glioma cells through the cell cycle depending upon the growth phase of the cells. (C) 1995 Wiley-Lis s, Inc.