Relationship of cellular topoisomerase III- inhibition to cytotoxicity and published genotoxicity of fluoroquinolone antibiotics in V79 cells

• Published in: Chemico-biological interactions Vol. 203; no. 2; pp. 386 - 390
• Main Authors: Williams, Gary, Brunnemann, Klaus, Smart, Daniel, Molina, David, Jeffrey, Alan, Duan, Jian-Dong, Krebsfaenger, Niels, Kampkoetter, Andreas, Schmuck, Gabriele
• Format: Journal Article
• Language: English
• Published: 01.04.2013
• ISSN: 0009-2797
• DOI: 10.1016/j.cbi.2013.01.003

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 III- 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 III-aDNA. Cytotoxicity was measured by relative cell counts.