Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.

The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.