title: Correlation between umuC induction and Salmonella mutagenicity assay for quinolone antimicrobial agents.
abstract: Quinolone antimicrobial agents induce the SOS response in bacteria, including the umuDC genes necessary for error-prone repair. Consequently these drugs may be mutagenic in bacteria with a functional SOS response. Differential killing tests with Escherichia coli WP2 (trp) and its repair-deficient derivative CM871 (trp lexA recA uvrA) indicated that a functional DNA repair system was protective against the action of quinolones, implying that quinolones are causing some form of DNA damage (not necessarily directly) and are therefore genotoxic. Dose-dependent reversion from His- to His+ with quinolones was observed in the Ames test with Salmonella typhimurium TA102 (uvr+) but in no other Salmonella tester strains (all uvr-), suggesting that a functional excision repair system is essential for quinolone-induced bacterial mutagenesis. A significant correlation between SOS inducing potential (SOSIP) and mutagenic potential in the Ames test (r = 0.89) indicated that quinolone-induced mutagenic effects in bacteria are almost entirely due to SOS-processed DNA damage.
authors.affiliation: Department of Microbiology, UMDS, St. Thomas' Hospital, London, UK.
authors.forename: E G
authors.initials: EG
authors.lastname: Power
authors.forename: I
authors.initials: I
authors.lastname: Phillips
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D004259:DNA-Directed DNA Polymerase; D015365:Enoxacin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D015964:Gene Expression Regulation, Bacterial; D009152:Mutagenicity Tests; D009268:Nalidixic Acid / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology; D009643:Norfloxacin / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; C054745:temafloxacin; D015365:Enoxacin; D009268:Nalidixic Acid; D002939:Ciprofloxacin; C047225:difloxacin; C078202:UmuC protein, E coli; D004259:DNA-Directed DNA Polymerase; C055185:tosufloxacin; D009643:Norfloxacin; C061363:sparfloxacin