Electrochemical characteristics of five quinolone drugs and their effect on DNA damage and repair in Escherichia coli. 1990

A Thomas, and J Tocher, and D I Edwards
Chemotherapy Research Unit, Polytechnic of East London, UK.

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.

UI MeSH Term Description Entries
D010584 Bacteriophage phi X 174 The type species of the genus MICROVIRUS. A prototype of the small virulent DNA coliphages, it is composed of a single strand of supercoiled circular DNA, which on infection, is converted to a double-stranded replicative form by a host enzyme. Coliphage phi X 174,Enterobacteria phage phi X 174,Phage phi X 174,phi X 174 Phage,Phage phi X174
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D004563 Electrochemistry The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. Electrochemistries
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000890 Anti-Infective Agents Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. Anti-Infective Agent,Anti-Microbial Agent,Antimicrobial Agent,Microbicide,Microbicides,Anti-Microbial Agents,Antiinfective Agents,Antimicrobial Agents,Agent, Anti-Infective,Agent, Anti-Microbial,Agent, Antimicrobial,Agents, Anti-Infective,Agents, Anti-Microbial,Agents, Antiinfective,Agents, Antimicrobial,Anti Infective Agent,Anti Infective Agents,Anti Microbial Agent,Anti Microbial Agents
D013014 SOS Response, Genetics An error-prone mechanism or set of functions for repairing damaged microbial DNA. SOS functions (a concept reputedly derived from the SOS of the international distress signal) are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after DNA repair, and possibly in cell death when DNA damage is extensive. SOS Response (Genetics),SOS Box,SOS Function,SOS Induction,SOS Region,SOS Repair,SOS Response,SOS System,Box, SOS,Function, SOS,Functions, SOS,Genetics SOS Response,Genetics SOS Responses,Induction, SOS,Inductions, SOS,Region, SOS,Regions, SOS,Repair, SOS,Repairs, SOS,Response, Genetics SOS,Response, SOS,Response, SOS (Genetics),Responses, Genetics SOS,Responses, SOS,Responses, SOS (Genetics),SOS Functions,SOS Inductions,SOS Regions,SOS Repairs,SOS Responses,SOS Responses (Genetics),SOS Responses, Genetics,SOS Systems,System, SOS,Systems, SOS
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections

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