Diphenylhydantoin and mitotic spindle abnormalities in cultured mouse and human cells

The present study demonstrates that the antiepileptic drug diphenylhydantoin (DPH) is capable of inducing aneuploidy but not structural aberrations in cultured mouse embryonic fibroblasts. A high concentration of 200 micrograms/ml was found to increase the percentage of hyperdiploidy from 4.8 (control) to 16.0. The treatment was found to increase mitotic indices as a consequence of a mitotic-arresting action of the drug. These effects are probably due to the effect of the drug on the structure of the mitotic apparatus. Abnormal cell divisions and mitotic disturbance were found to increase in a dose-dependent manner after DPH treatment. In a parallel study, human amnion cells were found to show similar response to DPH treatment.