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• W2070515910 abstract "Fluoroquinolone (FQ) antibiotics are bacteriocidal through inhibition of the bacterial gyrase and at sufficient concentrations in vitro, they can inhibit the homologous eukaryotic topoisomerase (TOPO) II enzyme. FQ exert a variety of genotoxic effects in mammalian systems through mechanisms not yet established, but which are postulated to involve inhibition of TOPO II enzymes. To assess the relationship of inhibition of cell nuclear TOPO II to cytotoxicity and reported genotoxicity, two FQ, clinafloxacin (CLFX) and lomefloxacin (LOFX), having available genotoxicity data showing substantial differences with CLFX being more potent than LOFX, were selected for study. The relative inhibitory activities of these FQ on nuclear TOPO IIα in cultured Chinese hamster lung fibroblasts (V79 cells) over dose ranges and at equimolar concentrations were assessed by measuring nuclear stabilized cleavage complexes of TOPO IIα-DNA. Cytotoxicity was measured by relative cell counts. Both FQ inhibited V79 cell nuclear TOPO IIα. The lowest-observed-adverse-effect levels for TOPO IIα inhibition were 55 μM for CLFX, and 516 μM for LOFX. The no-observed-adverse-effect-levels were 41 μM for CLFX, and 258 μM for LOFX. At equimolar concentrations (175 μM), CLFX was more potent than LOFX. Likewise, CLFX was more cytotoxic than LOFX. Thus, the two FQ, inhibited TOPO IIα in intact V79 cells, differed in their potencies and exhibited no-observed-adverse-effect levels. These findings are in concordance with published genotoxicity data and observed cytotoxicity." @default.
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• W2070515910 date "2013-04-01" @default.
• W2070515910 modified "2023-09-22" @default.
• W2070515910 title "Relationship of cellular topoisomerase IIα inhibition to cytotoxicity and published genotoxicity of fluoroquinolone antibiotics in V79 cells" @default.
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• W2070515910 doi "https://doi.org/10.1016/j.cbi.2013.01.003" @default.
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