Electrochemical characteristics of five quinolone drags and their effect on DNA damage and repair in Escherichia coli

Abstract

The object of this study was to determine whether 4-quinolone antimicrobials were reduced under biologically attainable redox conditions and whether they had any effect on DNA in the absence of the DNA gyrase enzyme. Electrochemical characteristics of the drugs were investigated using d c polarography, differential pulse polarography and cyclic voltammetry. The ability of the drugs to interact with, and cause damage to, naked DNA was investigated by a phi X174 DNA double transfection assay. Induction of DNA SOS repair was assessed using a stain of Escherichia coli in which the synthesis of beta-galactosidase was under the control of the su1A gene. Growth studies were performed using a conductimetric method in a Malthus system. All five 4-quinolones examined had redox potentials lower (more negative) than -1.2 V and thus were incapable of being reduced in biological systems, even under strict anaerobiosis. Exposure of all drugs to single-stranded phi X174 DNA for up to 50 h engendered no detectable damage. However, all the drugs induced DNA SOS repair, in the order ciprofloxacin greater than fleroxacin = pefloxacin greater than norfloxacin greater than nalidixic acid. This rank order corresponds approximately with antibacterial efficiency. The growth studies indicated that redoxyendonuclease III and excision repair enzymes may be involved in the fixation of quinolone-induced damage.