Effect of phenytoin on intracellular 45Ca2+ accumulation in gingival fibroblasts in vitro

Effect of 5,5 diphenylhydantoin (phenytoin; PHT) alone or in combination with epidermal growth factor (EGF) on the intracellular accumulation of the radioisotope 45Ca2+ (4 min labelling period) was determined in gingival fibroblasts. EGF as well as PHT increased the intracellular accumulation of the radioisotope in normal gingival fibroblasts by approximately 2 and 1.6-fold, respectively. In contrast, in fibroblasts derived from the phenytoin-induced gingival overgrowth, neither EGF nor PHT stimulated intracellular accumulation of 45Ca2+. When normal gingival fibroblasts were treated in vitro with EGF in combination with PHT, the EGF-induced increase in intracellular accumulation of the radioisotope 45Ca2+ was abolished. The rate of efflux of the radioisotope 45Ca2+ in prelabelled normal gingival fibroblasts was decreased by PHT treatment in vitro to a level already present in fibroblasts derived from PHT-induced gingival overgrowth. This study indicates that PHT influences the cellular calcium metabolism in fibroblasts which may contribute to the pathogenesis of gingival overgrowth.