ABSTRACT
The effect of phenytoin on the mitotic activity of gingival tissue as well as cultured mammalian fibroblasts was studied. This was measured quantitatively using autoradiography utilizing tritiated thymidine. Hyperplastic gingiva removed from patients treated with phenytoin and subjected to autoradiography showed a marked increase in the mitotic activity of gingival cells. This was also the case with cultured fibroblasts. The mitotic index was higher in the treated fibroblasts than that of the control. Ascorbic acid added to the cultures markedly reduced the mitotic activity of these cells. These results agree with other studies that phenytoin may be a factor in direct stimulation of the mitotic activity and gingival hyperplasia seen in patients taking this medication.
Subject(s)
Fibroblasts/drug effects , Gingiva/cytology , Mitosis/drug effects , Phenytoin/pharmacology , Animals , Ascorbic Acid/pharmacology , Autoradiography , Cells, Cultured , Gingiva/drug effects , Gingival Hyperplasia/chemically induced , Humans , Phenytoin/adverse effects , RatsABSTRACT
1. In the isolated rabbit ear vascular bed, perfused with Krebs solution, prostaglandins E(1) and F(2alpha) produce dose-dependent, phentolamine-sensitive constrictions.2. These are absent if the animal is pre-treated with reserpine or if the ear is denervated in advance.3. If noradrenaline or vasopressin is added to the Krebs solution, vascular resistance is high and PGE(1) and PGF(2alpha) produce vasodilatation which is unaffected by hyoscine or propranolol.4. Perfusion with theophylline, with added ATP, ADP or 3'5'-AMP, or pre-treatment of the animal with stilboestrol antagonizes the dilator response to PGE(1) in the presence of noradrenaline, which may be reversed. Most of the responses to PGF(2alpha) are reversed. These treatments elevate the level of 3'5'-AMP in tissues.5. It is postulated that prostaglandins exert a regulatory action on 3'5'-AMP levels through inhibition of adenyl cyclase and/or phosphodiesterase and that the resulting rising or falling level of 3'5'-AMP determines the nature of the response by the smooth muscle to the released noradrenaline.
