Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101

Hayasaki, Yayoi; Itoh, Satoru; Kato, Michiyuki; Furuhama, Kazuhisa

doi:10.1016/j.tiv.2005.08.004

Cited by 10 publications

(7 citation statements)

References 18 publications

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“…With respect to the genotoxicity of quinolones, in general, they have been reported to be positive for chromosomal aberrations in cultured mammalian cells, but negative for bacterial reverse mutations in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2uvrA [Shimada et al, 1992;Shimada and Itoh, 1996]. Moreover, many quinolones have been confirmed to exhibit mutagenicity in TA102 and in WP2uvrA/pKM101 [Ysern et al, 1990;Gocke, 1991;Mamber et al, 1993;Watanabe et al, 1998;Martínez et al, 2000;Hayasaki et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

Use of centromeric and telomeric DNA probes in in situ hybridization for differentiation of micronuclei induced by lomefloxacin

Attia

2009

Environ and Mol Mutagen

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Classification of micronuclei induced by lomefloxacin, a difluorinated quinolone bactericidal agent, in mouse bone marrow was performed by fluorescence in situ hybridization using DNA probes for the centromere repeated minor satellite DNA and the telomeric hexamer repeat (5'-TTAGGG-3'). Colchicine and mitomycin C were used as a positive control aneugen and clastogen, respectively, and these compounds produced the expected responses. Single doses of 40, 80, 160, or 320 mg/kg lomefloxacin were given via oral intubations and bone marrow was sampled at 24 and 48 hr after treatment. The micronuclei showed significant increases in both sampling times after doses of 320 mg/kg. A statistically significant increase of micronuclei frequency was also detected for 160 mg/kg lomefloxacin at 48 hr after treatment. The responses were directly correlated with bone-marrow cytotoxicity. Following treatment with 160 and 320 mg/kg lomefloxacin, 48.2 and 50.0% of the induced micronuclei, respectively, showed double labeling with centromeric signals and several telomeric signals, indicating that the induced micronuclei were composed of whole chromosomes. Similarly, 51.8 and 50.0% of the induced micronuclei, respectively, were centromere-negative, demonstrating that lomefloxacin not only induces chromosome loss but also chromosome breakage. The results also showed that chromosomes can be enclosed in a micronucleus before and after centromere separation. Overall, this study provides the first evidence of the potential of lomefloxacin to induce aneugenic effect in mice. However, given the high doses used in this study, the clinical significance of this finding is uncertain.

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Section: Introductionmentioning

confidence: 99%

Use of centromeric and telomeric DNA probes in in situ hybridization for differentiation of micronuclei induced by lomefloxacin

Attia

2009

Environ and Mol Mutagen

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“…coli WP2uvrA/pKM101 was proven to be a suitable strain for detecting the mutagenicity of quinolones (Hayasaki et al, 2006). In this study, the new strain of E. coli WP2uvrA/pKM101 showed low response to the mutagenicity of quinolones, although its response to the positive control compounds was almost the same as that of the strain used in the previous study.…”

Section: Discussionmentioning

confidence: 59%

“…In the previous study, twelve quinolones were separated into six groups according to their bactericidal effects (Hayasaki et al, 2006). In this study, six compounds were selected from each of the six groups because their mutagenicity in E. coli WP2uvrA/pKM101 was observed to be close to their bactericidal concentrations.…”

Section: Test Chemicals and Mediamentioning

confidence: 99%

“…The reverse mutation assay was carried out by the preincubation method described earlier (Hayasaki et al, 2006). Triplicate plates were used for each dose level.…”

Section: Reverse Mutation Assaysmentioning

confidence: 99%

“…Many studies have indicated that E. coli WP2uvrA/pKM101 is a susceptible strain for detecting numerous mutagens, especially oxidative and cross-linking agents (Wilcox et al, 1990;Watanabe et al, 1996Watanabe et al, , 1998aWatanabe et al, and 1998b. We have previously reported that twelve quinolone antibac--efloxacin, moxifloxacin, norfloxacin, ofloxacin, sita-E. coli WP2uvrA/pKM101 (Hayasaki et al, 2006). Furthermore, eleven quinolones, including ciprofloxacin, been shown to be mutagenic in S. typhimurium TA102 (Ysern et al, 1990;Gocke, 1991;Mamber et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Different responses in mutagenesis induced by quinolone antibacterial agents in two Escherichia coli WP2uvrA/ pKM101 strains

et al. 2009

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-Escherichia coli WP2uvrA/pKM101 strain obtained from a different supplier had a lower response to quinolone antibacterial agents (quinolones) when compared to an ordinary responsive strain. The present study was designed to examine the mechanism of lower susceptibility of the new strain to quinolones. A reverse mutation assay showed the new strain was low responsive to six quinolones compared to a responsive strain, while there was no difference in sensitivity to antibacterial activity of quinolones or the mutagenic activity of the positive control compounds in both strains. The sequence of mucA and B genes, which involve chemical and ultraviolet (UV) -induced mutagenesis through error-prone repair, and the total length of plasmid pKM101 in both strains were identical. Furthermore, transformed WP2uvrA/pKM101 strains, which were made by separately electroporating pKM101 extracted from these two strains into WP2uvrA, showed almost the same responses to the mugatenic-and antibacterial-activity of quinolones as the original responsive strain. The two original strains and the recipient WP2uvrA were proven to have proper genetic characteristics. It was demonstrated that the lower susceptibility of the new WP2uvrA/pKM101 strain to the mutagenesis of quinolones was not due to any changes in either plasmid pKM101 or the characteristics of the host detected by a routine check (tryptophan requirements, sensitivity to UV light and cell membrane permeability) of their genetic characteristics.

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A comparative analysis of chromosomal aberrations in cultured human lymphocytes due to fluoroquinolone drugs at different expression periods

2010

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Fluoroquinolones (FQ) are broad-spectrum antibacterial agents widely used for the treatment of infections with various types of gram negative and gram positive bacteria. Specifically, gatifloxacin (GFX) is under development as a component in a new antituberculosis fixed-dose drug combination. In the context of this project, GFX was also tested for genotoxic activity in human peripheral lymphocytes, and the induction of chromosomal aberrations by GFX in PHA-M stimulated cultured human lymphocytes, investigated under conditions of conventional and increased expression times, was further compared to the analogous effects induced by some other second- and third-generation FQ antibacterial agents, namely ofloxacin (OFX), ciprofloxacin (CFX) and sparfloxacin (SFX). OFX did not induce any significant chromosomal aberrations in human lymphocytes. CFX and SFX exhibited slight to moderate clastogenic potential at cytotoxic concentrations (150, 175, 200 and 225 microg/ml), and GFX, a third-generation FQ, induced a clear, concentration-dependent increase in the frequency of chromosomal aberrations at cytotoxic concentrations (150, 200 and 250 microg/ml). These effects were not apparent when metaphases were analysed at the conventionally used sampling time of 24 h, but only after prolongation of the expression time between treatment and harvesting to a sampling time of 36 h (4 h exposure and 32 h expression period). Also, an increased incidence of numerical aberrations (polyploidy and endoreduplication) was seen with GFX at non-cytotoxic concentrations (12.5, 25, 50 and 75 microg/ml). These effects can be attributed to the slight cross-reactivity of FQs between their inhibitory activity towards their intended targets, the prokaryotic type II topoisomerase enzymes DNA gyrase and topoisomerase IV, and the analogous mammalian enzyme topoisomerase II. We have also observed the formation of polycentrics, i.e., chromosomes with five to six centromeres, a rarely reported structural aberration, in GFX-treated cells. The significance of these observations with respect to the conventional conduct of such studies and to the interpretation of the effects is discussed.

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Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101

Cited by 10 publications

References 18 publications

Use of centromeric and telomeric DNA probes in in situ hybridization for differentiation of micronuclei induced by lomefloxacin

Use of centromeric and telomeric DNA probes in in situ hybridization for differentiation of micronuclei induced by lomefloxacin

Different responses in mutagenesis induced by quinolone antibacterial agents in two Escherichia coli WP2uvrA/ pKM101 strains

A comparative analysis of chromosomal aberrations in cultured human lymphocytes due to fluoroquinolone drugs at different expression periods

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