Response of Radiated Human Gingival Fibroblast-like Cells to Dilantin Sodium in Tissue Culture

¹ Indiana University School of Dentistry and School of Medicine, Departments of Oral Pathology and Pathology, Indianapolis, Indiana

The current studies were designed to aid in clarifying the mechanism through which diphenylhydantoin sodium (DPH) effects the metabolism of connective-tissue cells to increase their proliferative capacity.

The effects of X-ray radiation on normal HGF cells, in doses between 400 and 1,600 r, resulted in a varying degree of diminution of proliferation of cells. Maintenance of cells radiated with 400 r in continuous culture has resulted in a marked alteration of their metabolic pattern, as evidenced by a gradual alteration of their proliferation rate. The addition of DPH to actively growing cell cultures of these previously radiated cells resulted in a complete lack of the usual response to the drug, thus suggesting severe alteration in the internal metabolism of the cell. Further evidence of this alteration of metabolism is suggested by the somewhat increased resistance to levels of DPH found toxic to the normal HGF cell.

Tritiated thymidine uptake studies have also substantiated the stimulatory effect of DPH on normal HGF cells as reflected by a doubling of labeled nuclei in DPH-treated tubes as compared to control tubes at the 2-day period, probably indicating a marked increase in DNA synthesis. In contrast, while the per cent of labeled cells at the 2-day period was much greater in the 1° radiated HGF cell than in the normal HGF cell, no increase in nuclear labeling was found in the 1° radiated HGF cell treated with the drug, thus correlating with mean viable cell counts. In addition, there was a persistent high percentage of labeled nuclei at the 3-day period in the 1° radiated HGF cell in contrast to the normal HGF cell.

These current studies provide further evidence that diphenylhydantoin sodium is a true cell stimulatory agent for normal fibroblasts and that alteration in the normal metabolic pattern of such cells, as by radiation or as in neoplasia, can inhibit this effect of the drug.