Recombinagenic and mutagenic activities of fluoroquinolones in Drosophila melanogaster

Fluoroquinolones are widely used in human and in veterinary medicine due to their broad-spectrum antibacterial activity. They act by inhibiting type II DNA topoisomerases (gyrase and topoisomerase IV). Because of the sequence homology between prokaryotic and eukaryotic topoisomerases II, fluoroquinolones can pose a hazard to eukaryotic cells. However, published information concerning the genotoxic profiles of these drugs in vivo is sparse and inconsistent. We have assessed the activities of three fluoroquinolones, ciprofloxacin, enrofloxacin and norfloxacin, in the Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) and measured their mutagenic and recombinagenic potentials. Norfloxacin was non-genotoxic. Ciprofloxacin and enrofloxacin induced significant increases in spot frequencies in trans-heterozygous flies. To test the roles of somatic recombination and mutation in the observed genotoxicity, balancer-heterozygous flies were also analyzed. Ciprofloxacin and enrofloxacin were preferential inducers of homologous recombination in proliferative cells, an event linked to loss of heterozygosity.

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► Norfloxacin does not induce gene and chromosomal mutations or HR.
► Ciprofloxacin and enrofloxacin were classified as preferential inducers of HR.
► Mutational events contribute to less than 40% to cipro and enro genotoxicity.
► SMART test has proven to be useful for testing topo II inhibitors drugs.
► HR events should be assessed in investigations on the genotoxicity of quinolones.