title: Myofibroblasts in phenytoin-induced hyperplastic connective tissue in the rat and in human gingival overgrowth.
abstract: Phenytoin is a commonly used anticonvulsant drug for the prevention of seizures. A common side effect of phenytoin (PHT) therapy is connective tissue hyperplasia, particularly in the oral cavity manifesting as gingival overgrowth. Our previous studies concerning the molecular mechanisms of drug-induced gingival overgrowth have demonstrated that PHT alters the normal tissue turnover/wound healing signal by causing changes in macrophage phenotype, resulting in the upregulation of essential polypeptide growth factors such as platelet-derived growth factor (PDGF). The cellular consequences of this elevation in growth factor have not been investigated. The present light and electron microscopic study of rat hyperplastic connective tissue and human gingival overgrowth induced by PHT treatment revealed the presence of numerous myofibroblasts. Cells identified as myofibroblasts were evident in all PHT-treated tissue samples and were characterized by an elongated fusiform cell shape, abundant cytoplasmic rough endoplasmic reticulum/polyribosomes, and accumulations of sub-plasmalemmal microfilaments containing spindle densities. These cells were never observed in control tissues. Myofibroblasts are associated with the later stages of tissue turnover, specifically with the transition from the granulation to the remodeling phases of the wound healing process. The presence of myofibroblasts in hyperplastic connective and gingival tissues induced by PHT treatment suggests that PHT exacerbates the normal tissue turnover/wound healing signals responsible for the appearance of myofibroblasts.
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Dill
authors.forename: A M
authors.initials: AM
authors.lastname: Iacopino
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D018870:Endoplasmic Reticulum, Rough / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology*; D006097:Granulation Tissue / Q000187:drug effects / Q000473:pathology; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D010641:Phenotype; D010672:Phenytoin / Q000009:adverse effects*; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D011132:Polyribosomes / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D010672:Phenytoin