Mutagenic action of 5-nitroimidazoles: in vivo induction of GC-->CG transversion in two Bacteroides fragilis reporter genes.

The in vivo mutagenic potential of two 5-nitroimidazoles, metronidazole and dimetridazole, was evaluated in Bacteroides fragilis, a strictly anaerobic bacterium. Two antibiotic resistance genes, tetA(Q)3 and nimA, were used as DNA targets. The forward and back mutations were identified by nucleotide sequence analysis. Both drugs induced GC-->CG transversion exclusively. The results suggest that the reactive molecules generated during the intracellular reduction of the 5-nitroimidazoles are responsible for both base pair substitutions and DNA strand breaks, although the mechanisms and targets may be different.