The photomutagenicity of fluoroquinolones in tests for gene mutation, chromosomal aberration, gene conversion and DNA breakage (Comet assay).

Abstract

The ability of fluoroquinolones to cause light-induced adverse effects has been established in experimental studies and clinical observations. The formation of active oxygen species appears to be responsible for this activity. Photomutagenicity tests with bacterial, lower eukaryotic and mammalian cells were performed with three fluoroquinolones (Fleroxacin, Ciprofloxacin and Lomefloxacin). After concomitant irradiation with simulated solar light (with a reduced UVB component), weak increases in the number of revertants were observed in Salmonella typhimurium TA104 and TA100. No photomutagenic activity was detected in Saccharomyces cerevisiae D7. In the chromosomal aberration (CA) test with Chinese hamster V79 cells the number of aberrant metaphases was markedly increased. In the Comet assay with mouse lymphoma cells, evidence of extensive DNA breakage was obtained. All three compounds showed similar potencies in the Comet and Ames assays while there was a clear gradation of potencies in the CA assay (Lomefloxacin > Fleroxacin > Ciprofloxacin), which conformed with reports on the relative potencies regarding phototoxicity. The oxygen radical scavengers catalase, superoxide dismutase and N, N'-dimethylurea modulated the photoclastogenicity and phototoxicity but had no influence on the effects in the Comet and Ames tests. It thus appears that different kinds of mechanism are responsible for toxicity and clastogenicity on the one side and DNA breakage and gene mutation on the other side. Pre-irradiation of the test articles did not lead to enhanced genotoxicity, indicating the involvement of very short lived genotoxic agents. The results endorse the advice to avoid excessive light exposure during antibiotic therapy with fluoroquinolones.

• Authors: A A Chételat, S Albertini, E Gocke
• Journal: Mutagenesis (Mutagenesis) Vol. 11 Issue 5 Pg. 497-504 (Sep 1996) ISSN: 0267-8357 [Print] England
• PMID: 8921512 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Infective Agents
• Carcinogens
• Fluoroquinolones
• Mutagens
• Photosensitizing Agents
• Quinolones
• Ciprofloxacin
• lomefloxacin
• Fleroxacin
• Methoxsalen

Topics

• Animals
• Anti-Infective Agents (radiation effects, toxicity)
• Carcinogens (toxicity)
• Chromosome Aberrations
• Ciprofloxacin (chemistry, radiation effects, toxicity)
• Cricetinae
• DNA Damage (drug effects)
• Fleroxacin (chemistry, radiation effects, toxicity)
• Fluoroquinolones
• Gene Conversion (drug effects)
• Lymphoma (genetics, pathology, therapy)
• Methoxsalen (toxicity)
• Mice
• Mitosis (drug effects)
• Mutagenicity Tests (methods)
• Mutagens (toxicity)
• Mutation (drug effects)
• Photosensitizing Agents (toxicity)
• Quinolones (chemistry, radiation effects, toxicity)
• Saccharomyces cerevisiae (drug effects, genetics)
• Salmonella (drug effects, genetics)
• Tumor Cells, Cultured
• Ultraviolet Rays