Gingival enlargement caused by long-term treatment with the antiepileptic drug phenytoin will be studied. Two approaches will be utilized; 1) study of the lesion in mongrel cats. Drug metabolism and dose response will be determined. Any possible genetic component in terms of susceptibility or non-susceptibility to phenytoin-induced gingival enlargement will be ascertained by selective breeding. 2) study of human gingival fibroblasts in culture. Cells have been obtained from a total of 40 humans, including normal individuals, phenytoin-treated epileptics manifesting gingival enlargement, and similarly-treated epileptics refractory to development of the lesion. These cells will be studied in culture to test their protein and collagen synthetic activities and their level of production and release of collagenase and mucopolysaccharides. These cells will also be exposed to phenytoin and some of its major (human) metabolic breakdown products, to elucidate any possible direct drug-to-cell interaction. The hypothesis being investigated is that some cell subpopulations are sensitive to exogenous agents (e.g., phenytoin), while other, similar-appearing cells are not. An investigation of the putative heterogeneity of normal fibroblast population in vivo is antecedent to the hypothesis.
NIH ExPorter
NIH ExPorter