II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients

Lymphocyte proliferation kinetics (LPK) is an end point used in genetic toxicology that was proposed as an alternative for the screening of anticonvulsant drugs. The effect of phenytoin (PHT) was investigated on the mitotic and proliferation indices in cultured blood lymphocytes of 33 sporadically collected untreated and 42 PHT-treated epileptics, where the duration of treatment was 3, 6, and 9 months, and 40 control subjects (age range 10-30 years). PHT induced mitotic delays and decreased the mitotic index. A significant heterogeneity of the first, second and the third metaphases between treated and untreated groups was revealed. A reduction of the proliferation index (P < 0.001) and proliferation delay per cycle (P < 0.001) was also observed. There was little variation between the controls and untreated patients (P > 0.05). The results have confirmed that PHT can affect responses leading to genotoxicity. Teratogenesis Carcinog. Mutagen. 21:151-164, 2001.