Inhibition by diphenylhydantoin of growth and morphological differentiation of glial cells: Implication of calcium

Abstract

The effects of diphenylhydantoin (DPH) and other anticonvulsants on the growth of glial cells as well as neuroblastoma cell lines was studied. The DPH inhibition of the DNA synthesis was most marked in rat fetal glioblasts induced by glia maturation factor (GMF) among the cell lines studied, and that in C6 cells. The IC 50 of DPH for glioblasts and C6 cells were about 0.2 and 0.4 mM, respectively. The inhibitory effects of DPH and valproate on DNA synthesis was specific for glial cells, and the DNA synthesis of such neuronal cell lines as Neuro2a, NAs-1, and PC12 was unaffected at pharmacological concentrations. Diazepam inhibited the DNA synthesis of all cell types examined in the contrary to DPH, which preferentially inhibited glial cells. Phenobarbital showed no effect, and thiopental inhibition was <30% of the DNA synthesis in control condition with all cell lines used at the concentration of 0.4 mM. Both DPH and diazepam suppressed the extrusion induced by GMF of the glioblast processes, and the neuroblastoma cell neurites that had extended in the presence of dibutylyl cAMP disappeared by the exposure to DPH, suggesting that these drugs affected the cytoskeletal rearrangement of both glial and neuronal cells during morphological differentiation.