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 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 microg/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 microg/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.
Itoh
Tadashi
T
Laboratory of Veterinary Pathology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. kakuitou@yahoo.co.jp
Mitsumori
Kunitoshi
K
Kawaguchi
Satomi
S
Sasaki
Yu F
YF
D000890:Anti-Infective Agents / Q000633:toxicity*; D002869:Chromosome Aberrations; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008223:Lymphoma / Q000188:drug therapy; D015162:Micronucleus Tests; D009154:Mutation / Q000235:genetics; D015363:Quinolones / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000890:Anti-Infective Agents; D015363:Quinolones; D016159:Tumor Suppressor Protein p53