Genotoxic effects of metronidazole

Metronidazole (MTZ) is an effective agent used in the treatment of parasitic infections. Its genotoxic effects have been shown in a variety of prokaryotic systems; however, negative results have been reported in human in vivo studies. Due to its wide spread use, a study was performed to evaluate the chromosomal aberration frequencies in peripheral blood lymphocyte cultures from 10 individuals, before and after metronidazole treatment. A significant increase in the percentage of cells with chromatid and isochromatid breaks was observed after metronidazole treatment (1500 mg per day for 10 days). The percentages of cells with aberrations did not correlate with the levels of MTZ found in plasma. Individual variability was observed with respect to both the induction of aberrations and the concentration of MTZ in plasma. They could represent differences at the metabolic level, since metronidazole is known to be biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown mutagenic activity.