Genotoxic potential of quinolone antimicrobials in the in vitro comet assay and micronucleus test

The purpose of this study was to examine the genotoxicity of quinolone antimicrobials. We investigated the genotoxic potential of eight quinolones, namely nalidixic acid (NA), pipemidic acid (PPA), oxolinic acid (OA), piromidic acid (PA), enoxacin (ENX), ofloxacin (OFLX), norfloxacin (NFLX) and cipr...

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Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2006-02, Vol.603 (2), p.135-144
Main Authors: Itoh, Tadashi, Mitsumori, Kunitoshi, Kawaguchi, Satomi, Sasaki, Yu F.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Comet assay
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Genotoxicity
Medical sciences
Micronucleus test
Norfloxacin
Quinolone
Single strand breaks
Toxicology
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Summary:The purpose of this study was to examine the genotoxicity of quinolone antimicrobials. We investigated the genotoxic potential of eight quinolones, namely nalidixic acid (NA), pipemidic acid (PPA), oxolinic acid (OA), piromidic acid (PA), enoxacin (ENX), ofloxacin (OFLX), norfloxacin (NFLX) and ciprofloxacin (CPFX), by the in vitro alkaline single-cell gel electrophoresis (comet) assay at pH > 13. WTK-1 cells (mutant p53) were treated with each of the eight quinolones at 62.5–1000 μg/mL for 2, 4 and 20 h. NFLX and CPFX significantly induced DNA damage concentration-dependently after 4 and 20 h treatment, but this damage was recoverable. On the other hand, DNA was not damaged in the cells treated with six other quinolones. In the cells treated with NFLX and CPFX for 20 h, DNA migration was compared by the comet assay at pH 10, 12.1 and >13. The comet assay both at pH 12.1 and >13 showed increased DNA migration, but there was no positive response in the comet assay at pH 10. In the in vitro micronucleus (MN) test, WTK-1 cells were treated with each of four quinolones (NA, PPA, NFLX and CPFX) at 15.63–125 μg/mL for 20 h. NFLX significantly increased MNs in the cells, but no changes were noted in the cells treated with three other quinolones. These results suggest that NFLX and CPFX induced DNA single strand breaks (SSBs), and that NFLX-induced SSBs resulted in chromosome aberrations.
ISSN:1383-5718
1879-3592
DOI:10.1016/j.mrgentox.2005.11.003