6 MUTAGENICITY ASSAYS IN EXPOSURE BIOMONITORING OF PATIENTS RECEIVINGCARBAMAZEPINE FOR EPILEPSY OR TRIGEMINAL NEURALGIA

The mutagenic potential of carbamazepine (CBZ) therapy has been studie d in 37 patients undergoing long-term treatment with this drug. Of the total group, 23 patients suffered from epilepsy and 14 from trigemina l neuralgia. Thirty-one healthy subjects served as controls. Six mutag enicity assays with different end-points were performed. The possible cytogenetic alterations were evaluated by analyzing sister-chromatid e xchange frequencies (SCE), chromosome aberrations (CA), micronuclei (M N), proliferation indices (PRI), and mitotic indices. The Salmonella a ssay with and without microsomal activation served to measure urinary mutagenicity. The results show that CBZ leads to an increase in SCE (p < 0.01) and PRI (p < 0.05) but had no effect on the other cytogenetic parameters. CBZ was negative in the urine mutagenicity test. Plasma l evels of total CBZ, free CBZ and CBZ-10,ll-epoxide did not correlate w ith the cytogenetic alterations. Even though folic acid and gamma-glut amyltranspeptidase were significantly different in patients and contro ls, there was no significant association between these values and SCE or PRI. Patients with epilepsy and those with trigeminal neuralgia did not differ with respect to the end-points analyzed.