MYOFIBROBLASTS IN PHENYTOIN-INDUCED HYPERPLASTIC CONNECTIVE-TISSUE INTHE RAT AND IN HUMAN GINGIVAL OVERGROWTH

PHENYTOIN IS A COMMONLY USED anticonvulsant drug for the prevention of seizures. A common side effect of phenytoin (PHT) therapy is connecti ve tissue hyperplasia, particularly in the oral cavity manifesting as gingival overgrowth. Our previous studies concerning the molecular mec hanisms of drug-induced gingival overgrowth have demonstrated that PHT alters the normal tissue turnover/wound healing signal by causing cha nges in macrophage phenotype, resulting in the upregulation of essenti al polypeptide growth factors such as platelet-derived growth factor ( PDGF). The cellular consequences of this elevation in growth factor ha ve not been investigated. The present light and electron microscopic s tudy of rat hyperplastic connective tissue and human gingival overgrow th induced by PHT treatment revealed the presence of numerous myofibro blasts. Cells identified as myofibroblasts were evident in all PHT-tre ated tissue samples and were characterized by an elongated fusiform ce ll shape, abundant cytoplasmic rough endoplasmic reticulum/polyribosom es, and accumulations of subplasmalemmal microfilaments containing spi ndle densities. These cells were never observed in control tissues. My ofibroblasts are associated with the later stages of tissue turnover, specifically with the transition from the granulation to the remodelin g phases of the wound healing process. The presence of myofibroblasts in hyperplastic connective and gingival tissues induced by PHT treatme nt suggests that PHT exacerbates the normal tissue turnover/wound heal ing signals responsible for the appearance of myofibroblasts.