Ultrastructural quantitation has been used to determine both the effect of phenytoin (PHT) on gingival connective tissue components and the cellular basis for these changes. The results suggest that the amount of ground substance increases, and this may be due to decreased degradation within fibroblasts.
Get full access to this article
View all access options for this article.
References
1.
Angelopoulos, A.P.: Diphenylhydantoin Gingival Hyperplasia - A Clinicopathological Review. 1) Incidence, Clinical Features and Histopathology . 2) Aetiology, Pathogenesis, Differential Diagnosis and Treatment, J Can Dent Assoc41: 103-106, 275-277, 1975.
2.
Gardner, A.F. , Gross, S.G.; and Wynne, L.E.: An Investigation of Gingival Hyperplasia Resulting from Diphenylhydantoin Sodium Therapy in Seventy-seven Mentally Retarded Patients, Exp Med Surg20:133-158, 1962.
3.
Aas, E. : Hyperplasia Gingivae Diphenylhydantoinae: A Clinical Histochemical and Biochemical Study, Acta Odontol Scand21:Suppl #34, 1963.
4.
Livingston, S. and Livingston , H.L.: Diphenylhydantoin Gingival Hyperplasia , Am J Dis Child117(3):265-270, 1969.
5.
King, J.D. and Gimson, A.P.: Experimental Investigation of Paradontal Disease in the Ferret and Related Lesions in Man, Br Dent J83:148-149, 1947.
6.
Nuki, K. and Cooper, S.H.: The Role of Inflammation in the Pathogenesis of Gingival Enlargement During the Administration of Diphenylhydantoin Sodium in Cats, J Periodont Res7:102-110,1972.
7.
Kristensen, C.B. : One-sided Gingival Hyperplasia After Treatment with Diphenylhydantoin, Acta Neurol Scand56:353-356, 1977.
8.
Staple, P.H. ; Reed, M.J.; Mashimo , P.A.; Sedransk, N.; and Umemoto, T.: Diphenylhydantoin Gingival Hyperplasia in Macaca arctoides: Prevention by Inhibition of Dental Plaque Deposition, J Periodontol49(6):310-325, 1978.
9.
Ishikawa, H. and Glickman, I.: Gingival Response to the Systemic Administration of Sodium Diphenylhydantoin (Dilantin) in Cats, J Periodontol32:149-158, 1961.
10.
Conard, G.J. ; Jeffay, H.; Boshes , L.; and Steinberg, A.D.: Levels of 5,5-diphenylhydantoin and its Major Metabolite in Human Serum, Saliva, and Hyperplastic Gingiva, J Dent Res53(6):1323-1329, 1974 .
11.
Kimball, O.P. : Treatment of Epilepsy with Sodium Diphenylhydantoinate , JAMA112:1244, 1939.
12.
Ziskin, D.E. ; Stowe, L.R.; and Zegarelli , E.V.: Dilantin Hyperplastic Gingivitis: 1. Its Cause and Treatment. 2. Differential Appraisal, Am J Ortho Oral Surg27:350-363, 1941.
13.
Stern, L.; Eisenbud, L.; and Klatell, J.: Analysis of Oral Reactions to Dilantin Sodium, J Dent Res22:157, 1943.
Brandon, S.A. : Treatment of Hypertrophy of the Gingival Tissue Caused by Dilantin Sodium Therapy, JADA37 :732-734, 1948.
16.
Staple, P.H. : Some Tissue Reactions Associated with 5,5-Diphenylhydantoin (Dilantin) Sodium Therapy, Br Dent J95:289-302, 1953.
17.
Panuska, H.J. ; Gorlin, R.J.; Bearman , J.E.; and Mit-Chell , D.F.: The Effect of Anticonvulsant Drugs Upon the Gingiva - A Series of Analyses of 1048 Patients. Part 1, J Periodontol31:336-344, 1960.
18.
Babcock, J.R. : Incidence of Gingival Hyperplasia Associated with Dilantin Therapy in a Hospital Population, JADA71(6): 1477-1450, 1965.
19.
King, D.A., Hawes, R.R.; and Bibby, B.G.: The Effect of Oral Physiotherapy on Dilantin Gingival Hyperplasia , J Oral Pathol5:1-7, 1976.
20.
Larmas, L.A. and Paunio, K.U.: Epithelial Hyperplasia in Hydantoin-induced Hyperplastic and Normal Human Gingivae, Proc Finn Dent Soc72:177-179, 1976.
21.
Lancial, L.A. ; Rowe, D.J., Hill , M.W.; and Hall, B.K.: Diphenylhydantoin Gingival Overgrowth in theFerret: Histological Quantitation, AADR Progr & Abst 59: No. 436, 1980.
22.
Shafer, W.G. : Effect of Dilantin Sodium on Growth of Human Fibroblast-like Cell Cultures, Proc Soc Exp Biol Med104:198-201, 1960.
23.
Ebadi, M.S. and Scott, P.M.: Increase in Collagen Level by Diphenylhydantoin as Possible Mechanisms of Drug-induced Gingival Hyperplasia , Clin Tox4(1):39-46, 1971.
24.
Fine, A.S.; Scopp, I.W. ; Egnor, R.; Froum, S. ; Thaler, R.; and Stahl, S.S.: Subcellular Distribution of Oxidative Enzymes in Human Inflamed and Dilantin Hyperplastic Gingiva,Arch Oral Biol19(7):565-571, 1974.
25.
Kasai, S. and Hachimine, K.: Effect of 5,5-Diphenylhydantoin Sodium on the Synthesis of Collagen by Some Fibroblastic Cell Lines Including Gingiva Derived Cells, Bull Tokyo Dent Coll15(2):53-62, 1974.
Hassell, T. ; Page, R.; Swanson , C.; and Kuzan, F.: Analysis of Possible Mechanisms in Dilantin-induced Gingival Fibrosis, AADR Progr & Abst56:No. 410, 1977.
28.
Hanstrom, L. ; Lerner, U.; and Gustafson, G.T.: The Effect of Diphenylhydantoin Upon Enzyme Release in Relation to Collagen Degradation in Cat Palatal Mucosa During Organ Culture, Med Biol57:171-176, 1979.
29.
Rose, G.G. and Robertson, P.B.: Collagenolysis by Human Gingival Fibroblast Cell Lines, J Dent Res56(4): 416-424, 1977.
30.
Keith, D.A. ; Paz, M.A.; and Gallop, P.M.: The Effect of Diphenylhydantoin on Fibroblasts in vitro, J Dent Res56(10): 1279-1283, 1977.
31.
Noess, T.: The Effect of 5,5-Diphenylhydantoin (Dilantin) on Fibroblast-like Cells in Culture, J Periodont Res4(2): 163-164, 1969.
32.
Robineaux, R.; Lorans, G.; and Beaure d'Augèris, C.: Action of Diphenylhydantoin on the Growth and Respiration of Cells in Culture, Rev Europ Etudes Clin et Biol15: 1066-1071, 1970 .
33.
Liu, T.Z. and Bhatnager, R.S.: Inhibition of Proto collagen Proline Hydroxylase by Dilantin, Proc Soc Exp Biol Med142: 253-255, 1973.
34.
Goultschin, J. and Shoshan, S.: Inhibition of Collagen Breakdown by Diphenylhydantoin , Biochim Biophys Acta631:188-191,1980.
35.
Haim, G.: Elektronenmikroskopische Untersuchen über die Hydantoin-hyperplasie der Gingiva bei Epileptikern. Les Parodontopathies, Rapports et Communications, XIVeme Congress de l'Association pour les Recherches les Parodontopathies (ARPA Internationale) , Vene Tipografia Luigi Salvangno, 1955, pp. 197-204.
36.
Van Der Kwast, W.A.M.: Speculations Regarding the Nature of Gingival Hyperplasia due to Diphenylhydantoin-sodium, Acta Med Scand153:399-405, 1956.
37.
Abadom, P.N. : The Pathological Reactions and Metabolism of 5:5 Diphenylhydantoin in the Ferret, Ph.D. dissertation, University of Rochester, New York, 1959.
38.
Houck, J.C. ; Jacob, R.A.; and Maengwyn-Davus , G.D.: The Effect of Sodium Dilantin Administration Upon the Chemistry of the Skin, J Clin Invest39:1758-1762, 1960 .
39.
Bhussry, B.R. and Rao, S.: Effect of Sodium Diphenylhydantoinate on Oral Mucosa of Rats, Proc Soc Exp Biol Med113:595-597, 1963.
40.
Angelopoulos, A.P.: Histopathological, Histochemical and Quantitative Studies of Mast Cells in Hyperplasia Gingivae Diphenylhydantoinae, Ph.D. dissertation , University of Rochester, New York , 1966.
41.
Ballard, J.B. and Butler, W.T.: Proteins of the Periodontium. Biochemical Studies on the Collagen and Noncollagenous Proteins of Human Gingivae , J Oral Pathol3(4) : 176-184, 1974.
42.
Schneir, M. ; Ogata, S.; and Fine, A.: Confirmation That Neither Phenotype nor Hydroxylation of Collagen is Altered in Overgrowth Gingivae from Diphenylhydantoin-treated Patients, J Dent Res57(3): 506-510, 1978.
43.
Hanstrom, L. and Jones, I.L.: The Effect of Diphenylhydantoin Upon Degradation of Sulphated Macromolecules in Cat Palatal Mucosa in vitro , Med Biol57:177-181, 1979.
44.
Hiramatsu, M.; Hatakijama, K.; Abe , I.; and Minami, N.: The Effect of Diphenylhydantoin Sodium on Acid Mucopolysaccharide and Collagen Contents of Cotton Pellet Granulomas in Rats, J Periodont Res14:173-177, 1979.
45.
Hassell, T.M. ; Page, R.C.; and Lindhe, J.: Histologic Evidence for Impaired Growth Control in Diphenylhydantoin Gingival Overgrowth in Man , Arch Oral Biol23:381-384, 1978.
46.
Kaemmerer, E. and Elmering, G.: Zum Entstehungsmodus der Gingivitus Hyperplastic der Epileptiker, Med Klin60:1273-1277, 1965.
47.
Tsutsumi, V.F. ; Hara-Ortiz, F.; and Alvarez-Fuer-Tes , G.: La Hiperplasia Gingival en Enfermos Epilepticos
48.
Tratados con Difenihidantona. Estudio con el Microscopio de Luz y Electronic , Rev Invest Salud Publica (Mexico)33:1, 1973.
49.
Steinberg, A.D. ; Alvarez, J.; and Jeffay, H.: Lack of Relationship Between the Degree of Induced Gingival Hyperplasia and the Concentration of Diphenylhydantoin in Various Tissues of Ferrets, J Dent Res51(2):657-662, 1972.
50.
King, J.D.: Experimental Production of Gingival Hyperplasia in Ferrets Given "Epanutin" (Sodium Diphenylhydantoinate), Br J Exp Pathol33:491-498, 1952.
51.
Steinberg, A.D. ; Allen, P.M.; and Jeffay, H.: Distribution and Metabolism of Diphenylhydantoin in Oral and Normal Tissues of Ferrets , J Dent Res52(2):261-270, 1973.
52.
Dill, W.A.; Kazenko, A.; Wolf, L.M.; and Glazko, A.J.: Studies on 5,5-Diphenylhydantoin in Animals and Man, J Pharmacol Exp Ther118:270-279, 1956.
53.
Loë, H. and Silness, J.: Periodontal Disease in Pregnancy, I. Prevalence and Severity, Acta Odont Scand21:533-551, 1963.
54.
Silness, J. and Loë, H.: Periodontal Disease in Pregnancy. II. Correlation Between Oral Hygiene and Periodontal Condition, Acta Odont Scand22:121-135, 1964.
55.
Karnovsky, M.J.: A Formaldehyde-Glutaraldehyde Fixative of High Osmolality for Use in Electron Microscopy, J Cell Biol27 :137A, 1965.
56.
Warshawsky, H. and Moore, G.: A Method of Fixation and Decalcification for Electron Microscopy, Anat Res151: 431,1965.
57.
Robertson, P.B.; Ryel, R.B.; Taylor , R.E.; Shyu, K.W.; and Fullmer, H.M.: Collagenase: Localization in Polymorphonuclear Leukocyte Granules in the Rabbit, Science177:64-65, 1972.
58.
Ten Cate, A.R. and Deporter, D.A.: The Degradative Role of the Fibroblast in the Remodelling and Turnover of Collagen in Soft Connective Tissue, Anat Rec182:1-14, 1975.
59.
Mayahara, H. ; Hirano, H.; Saito , T.; and Ogawa, K.: The New Lead Citrate Method for the Ultracytochemical Demonstration of Non-specific Alkaline Phosphate (Orthophosphoric Mono-ester Phosphohydrase), Histochemie11 :88-96, 1967.
60.
Weibel, E.R.: Stereological Methods. In: Practical Methods for Biological Morphometry, Vol. 1, London : Academic Press, 1979, pp. 101-111.
61.
Schroeder, H.E. and Munzel-Pedrazzoli , S.: Correlated Morphometric and Biochemical Analysis of Gingival Tissue, J Microsc99:301-329, 1973.
62.
Schroeder, H.E.: Differentiation of Human Oral Stratified Epithelia, Basel : S. Karger, 1980, p. 246.
63.
Snedecor, G.W. and Cochran, W.G.: Statistical Methods, Ames, Iowa: Iowa State University Press.
64.
Chavrier, C. and Couble, M.L.: Ultrastructure du Chorion Conjonctif dans l'Hyperplasie Gingival Héréditaire, J Biol Buccale7:191-203, 1979.
65.
Squier, C.A. , Johnson, N.W.; and Hopps, R.M.: Human Oral Mucosa. Development, Structure and Function, Oxford: Blackwell Scientific Publications, 1976, p. 119.
66.
Kantor, M.L. and Hassell, T.M.: Increased Glycosaminoglycan Accumulation in Cultures of Human Fibroblasts from Phenytoin-induced Gingival Overgrowth , J Dent Res, In press.
67.
Sodek, J.: A Comparison of the Rates of Synthesis and Turnover of Collagen and Non-collagen Proteins in Adult Rat Periodontal Tissues and Skin Using a Microassay , Arch Oral Biol22:655-665, 1977.