EVALUATION OF THE GENOTOXIC ACTIVITY OF METRONIDAZOLE AND DIMETRIDAZOLE IN HUMAN-LYMPHOCYTES BY THE COMET ASSAY

The genotoxicity of metronidazole (MZ) and dimetridazole (DZ) has been evaluated in human lymphocytes using the comet assay. The test has be en performed using 3 doses (58.4, 175.2 and 292.1 mu M for MZ; and 70. 9, 212.6 and 354.3 mu M for DZ) under 3 experimental protocols: aerobi osis, anaerobiosis (90% N-2, 10% CO2) and with the presence of the mic rosomal fraction S9 mix. The effects of 4 antioxidants (8-hydroxyquino line (8HQ), vitamin C (VitC), catalase (CAT) and superoxide dismutase (SOD), have been investigated on DNA damage generated by fixed concent rations of MZ (292.1 mu M) and DZ (354.4 mu M). In aerobic conditions, MZ and DZ produced significant dose-response relationships. The dose- related effects of both drugs decreased or were abolished in anaerobic conditions or in presence of S9 mix. 8HQ, VitC, CAT and SOD induced d ose-related protective responses against DNA damage due to MZ and DZ, These findings suggest that MZ and DZ induce DNA damage in human lymph ocytes through the futile cycle, The one-electron reduction of the dru gs leads to the production of nitro radical anions. In the presence of oxygen, these radicals are reoxidized and generate oxygen-activated s pecies.