Study of potential in vitro and in vivo genotoxicity in hepatocytes of quinolone antibiotics.
The genotoxicity of quinolone antibiotics has been evaluated in hepatocytes following in vitro and in vivo exposure. Unscheduled DNA synthesis (UDS) was induced in vitro in rat hepatocytes by norfloxacin, ofloxacin, pefloxacin, and ciprofloxacin but not by nalidixic acid. In vivo UDS was not observed in hepatocytes isolated 4 to 24 hr after exposure of adult male F344 rats to either a single dose (30 to 190 mg/kg) or repeated doses (40 mg/kg) of ciprofloxacin. Using the 32P-postlabeling technique, no modified bases were detected in hepatocytes exposed in vitro to ciprofloxacin. In summary, UDS was induced in hepatocytes by in vitro exposure to high concentrations of norfloxacin, ofloxacin, pefloxacin, or ciprofloxacin. There was no evidence of in vitro DNA adduct formation by ciprofloxacin or in vivo DNA damage under the conditions tested. These findings suggest that ciprofloxacin is not DNA reactive, but it induces in vitro UDS as a consequence of some indirect action.
McQueen
C A
CA
American Health Foundation, Valhalla, New York 10595.
Way
B M
BM
Queener
S M
SM
Schlüter
G
G
Williams
G M
GM
D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000009:adverse effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009643:Norfloxacin / Q000009:adverse effects; D015242:Ofloxacin / Q000009:adverse effects; D015366:Pefloxacin / Q000009:adverse effects; D010761:Phosphorus Radioisotopes; D051381:Rats
D000890:Anti-Infective Agents; D010761:Phosphorus Radioisotopes; D015366:Pefloxacin; D002939:Ciprofloxacin; D004247:DNA; D015242:Ofloxacin; D009643:Norfloxacin