Influence of phenytoin on cytoplasmic free Ca2+ level in human gingival fibroblasts

Influence of 5,5-diphenylhydantoin (phenytoin; PHT) on the cytoplasmic free Ca2+ concentration, [Ca2+]i, was studied in fura 2 loaded adherent monolayers of human gingival fibroblasts derived from three patients before and after 9 months of PHT therapy. In the patient where gingival overgrowth developed during PHT medication (responder), addition of PHT to gingival fibroblasts derived before PHT medication induced a transient extracellular Ca2+ dependent increase in [Ca2+]i. In a non-responder patient, where gingival overgrowth did not develop during the same period of PHT therapy, addition of PHT to gingival fibroblasts derived before the start of medication did not significantly affect [Ca2+]i. Under extracellular Ca2+ deficient conditions, addition of PHT to serum-starved fibroblasts derived from the two categories of patients before the medication resulted in an increase in [Ca2+]i. In fibroblasts derived from the responder patient during PHT medication, in contrast to those from the non-responders (n = 2), the basal level of [Ca2+]i was significantly decreased. The results indicate that, in the cases studied, there is a relationship between PHT induced alterations in [Ca2+]i in gingival fibroblasts and the clinical development of gingival overgrowth.