Photogenotoxicity of Fluoroquinolones in Chinese Hamster V79 Cells: Dependency on Active Topoisomerase II

Snyder, Ronald D.; Cooper, Curt S.

doi:10.1111/j.1751-1097.1999.tb03288.x

Cited by 7 publications

(2 citation statements)

References 25 publications

(21 reference statements)

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“…It has been shown previously that lomefloxacin is a clastogen capable of inducing micronuclei in SKH1 hairless mice [Itoh et al, 2002a], Chinese hamster V79 cells [Kersten et al, 1999;Synder and Cooper, 1999], and HaCaT cells [Zhang et al, 2001] in conjunction with high UVA/UVB irradiation doses. Lomefloxacin can also enhance chromosomal aberrations in Chinese hamster lung cells with light irradiation in vitro [Itoh et al, 2002b].…”

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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“…Their mechanism of action relies on their ability to inhibit the bacterial gyrase, an enzyme involved in DNA replication, recombination and repair. Although the exact mechanism of inhibition remains unclear, quinolones are thought to interact ¶Posted on the website on 16 directly with DNA in synergy with the bacterial gyrase (1)(2)(3), the equivalent of the mammalian topoisomerase II. However, some quinolones show adverse side effects, such as skin phototoxicity (4), photomutagenicity and photocarcinogenicity upon UVA irradiation (5,6).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Fluoroquinolone-mediated Photosensitization of 2′-Deoxyguanosine, Calf Thymus and Cellular DNA: Determination of Type-I, Type-II and Triplet-Triplet Energy Transfer Mechanism Contribution¶

Sauvaigo¹,

Douki²,

Odin³

et al. 2007

Photochemistry and Photobiology

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Fluoroquinolone (FQ) antibacterials are known to exhibit photosensitization properties leading to the formation of oxidative damage to DNA. In addition, photoexcited lomefloxacin (Lome) was recently shown to induce the formation of cyclobutane pyrimidine dimers via triplet-triplet energy transfer. The present study is aimed at gaining further insights into the photosensitization mechanisms of several FQ including enoxacin (Enox), Lome, norfloxacin (Norflo) and ofloxacin (Oflo). This was achieved by monitoring the formation of DNA base degradation products upon UVA-mediated photosensitization of 2deoxyguanosine, isolated and cellular DNA. Oflo and Norflo act mainly via a Type-II mechanism whereas Lome and, to a lesser extent, Enox behave more like Type-I photosensitizers. However, the extent of oxidative damage was found to be relatively low. In contrast, it was found that cyclobutane thymine dimers represent the major class of damage induced by Enox, Lome and Norflo within isolated and cellular DNA upon UVA irradiation. This striking observation confirms that FQ are able to promote efficient triplet energy transfer to DNA. The levels of photosensitized formation of strand breaks, alkali-labile sites and oxidative damage to cellular DNA, as measured by the comet assay, were confirmed to be rather low. Therefore, we propose that the phototoxic effects of FQ are mostly accounted for energy transfer mechanism rather than by Type-I or -II photosensitization processes.

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Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians

Golomb,

Berg,

Han

2024

Sci Rep

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We evaluated whether veterans with Gulf War illness (VGWI) report greater ionizing radiation adverse effects (RadAEs) than controls; whether radiation-sensitivity is tied to reported chemical-sensitivity; and whether environmental exposures are apparent risk factors for reported RadAEs (rRadAEs). 81 participants (41 VGWI, 40 controls) rated exposure to, and rRadAEs from, four radiation types. The relations of RadAE-propensity (defined as the ratio of rRadAEs to summed radiation exposures) to Gulf War illness (GWI) presence and severity, and to reported chemical-sensitivity were assessed. Ordinal logistic regression evaluated exposure prediction of RadAE-propensity in the full sample, in VGWI, and stratified by age and chemical-sensitivity. RadAE-propensity was increased in VGWI (vs. controls) and related to GWI severity (p < 0.01) and chemical-sensitivity (p < 0.01). Past carbon monoxide (CO) exposure emerged as a strong, robust predictor of RadAE-propensity on univariable and multivariable analyses (p < 0.001 on multivariable assessment, without and with adjustment for VGWI case status), retaining significance in age-stratified and chemical-sensitivity-stratified replication analyses. Thus, RadAE-propensity, a newly-described GWI-feature, relates to chemical-sensitivity, and is predicted by CO exposure—both features reported for nonionizing radiation sensitivity, consistent with shared mitochondrial/oxidative toxicity across radiation frequencies. Greater RadAE vulnerability fits an emerging picture of heightened drug/chemical susceptibility in VGWI.

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Photogenotoxicity of Fluoroquinolones in Chinese Hamster V79 Cells: Dependency on Active Topoisomerase II

Cited by 7 publications

References 25 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

Analysis of Fluoroquinolone-mediated Photosensitization of 2′-Deoxyguanosine, Calf Thymus and Cellular DNA: Determination of Type-I, Type-II and Triplet-Triplet Energy Transfer Mechanism Contribution¶

Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians

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