Genotoxicity of the anticonvulsant drug phenytoin (PHT): A follow-up studyof PHT-untreated epileptic patients. II. Mitotic index (MI) and proliferation kinetics

The mitotic index and proliferation rate index were investigated to determi ne the effect of phenytoin (PHT) in cultured blood lymphocytes of epileptic s prior to and following administration of PHT over a period of 9 months (g rouped in multiples of 3 months) and 40 control subjects (age range 10-30 y ears). Treatment with PHT brought inhibition of the mitotic index (MI) and proliferation rate index (PRI), which were significantly higher in treated subjects or which were more expressive in treated lymphocytes (P < 0.001) f or all the three durations of treatment. In addition, statistically signifi cant heterogeneity of first, second, and third metaphases between the treat ed, untreated, and control subjects was found. Mean PRI values were used to estimate cell cycle delays, showing the highest effect in treated lymphocy tes (P < 0.001). There was no considerable variation between the control an d untreated (P > 0.05). The study demonstrates that PHT may be potentially genotoxic and hence the usefulness of MI and PRI in monitoring epileptics o n anticonvulsant treatment. (C) 1999 Wiley-Liss, Inc.