Growth-inhibitory effects of diphenylhydantoin on human brain tumor cells in culture.

Diphenylhydantoin (DPH, phenytoin sodium, Dilantin) inhibited the growth of cultured human astrocytoma cells in 7 of the 10 cell lines studied. This inhibition, determined by a microtiter assay, was dose-dependent; DPH levels of 20 micrograms/ml and above produced significant depression of growth in astrocytoma cultured cells. However, normal cultured human astrocytes were not affected until DPH levels of 60 micrograms/ml and above were added to the cells; normal fibroblasts also showed no growth inhibition up to 100 micrograms/ml. We have confirmed that DPH is 1.5 times as concentrated in tumor tissue as it is in normal tissue and serum. These findings suggest that DPH has properties that inhibit the growth of human astrocytoma cells in tissue culture at levels that are achievable clinically.