Phenytoin (PHT) has been suspected of having a mutagenic effect with chronic administration, but the existing evidence is equivocal. Contradictory results have been obtained using different testing systems. Sister chromatid exchange (SCE), a sensitive indicator of genotoxic environmental influences, has been used in only a few limited studies of PHT users, with varying results. The present study was designed to evaluate the potential mutagenicity of PHT in a more objective and reliable way than has been done previously. Following careful screening procedures, 16 adult male patients with epilepsy receiving long-term PHT monotherapy and 16 healthy controls were selected for a study of SCE frequencies in peripheral lymphocytes. The patients and controls were matched for sex, age, and smoking habits. Strict exclusionary criteria were observed, including all factors known to affect or suspected of affecting the SCE frequencies. Statistical analyses did not reveal any significant differences between the SCE rates of PHT-treated patients and controls, indicating a lack of PHT mutagenicity as expressed by induction of SCE in adults.
The potential of the widely prescribed antiepileptic drugs (AEDs) phenytoin (PHT) and phenobarbital (PB) to interact with genetic material was tested using sister chromatid exchange (SCE) assay. Thirty adult male patients with epilepsy receiving long-term AED therapy (16 with PHT, 6 with PB, and 8 with combined PHT and PB therapy) and 30 healthy controls were selected for the study of SCE frequencies in peripheral lymphocytes. The patients and controls were carefully screened and matched for sex, age, and smoking habits. All potential probands with exposure to factors known or suspected of affecting the SCE frequencies were excluded. Statistical analyses did not show any significant differences between the SCE rates of PHT- and/or PB-treated patients and controls, indicating a lack of mutagenicity of the tested drugs as expressed by induction of SCE on adult recipients. Smoking, however, affected the SCE levels considerably. The smokers had higher SCE frequencies than the nonsmokers, both among patients and controls. Caffeine consumption was also associated with SCE increases in patients but not in controls.
The potential of phenobarbital to interact with DNA has been studied using the sister chromatid exchange (SCE) assay in peripheral lymphocytes of nine adult male patients with epilepsy and of their matched controls. All patients were otherwise healthy individuals, treated chronically with phenobarbital in monotherapy. No statistically significant differences in SCE levels were found between the patient and control groups. Smoking was associated with increased SCE frequencies. The experiment was repeated with five available patients, using a slightly modified methodology. Although different SCE scores were obtained, the results of both tests were comparable.
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