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.
Trinh
S
S
Unité des Anaérobies, Institut Pasteur, Paris, France.
Reysset
G
G
D000595:Amino Acid Sequence; D001441:Bacteroides fragilis / Q000235:genetics*; D001483:Base Sequence; D004269:DNA, Bacterial; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D009593:Nitroimidazoles / Q000494:pharmacology*; D010957:Plasmids; D013753:Tetracycline Resistance / Q000235:genetics
D004269:DNA, Bacterial; D009153:Mutagens; D009593:Nitroimidazoles; C052587:4-nitroimidazole