Ciprofloxacin: mammalian DNA topoisomerase type II poison in vivo.
Ciprofloxacin (CF), a fluoroquinolone widely used as a potent antimicrobial drug, was evaluated in vivo in mouse bone marrow cells for its ability to induce clastogenicity and DNA damage in terms of increased sister-chromatid exchange (SCE) frequencies. Doses of 0.6, 6 and 20 mg/kg body weight of CF given intraperitoneally induced a positive dose-dependent significant clastogenicity (trend test alpha < or = 0.05), though the effects were not specific for specific phases of the cell cycle. The DNA-damaging effect observed as increased SCE frequencies using doses of 0.15, 0.30, 0.60, 1.2 and 6 mg/kg body weight showed a significant dose-dependent increase (trend test alpha < or = 0.05; lowest effective concentration 1.2 mg/kg of body weight). Compared to a potent eukaryotic DNA topoisomerase type II poison, etoposide (VP-16, 0.5, 1 and 5 mg/kg body weight, given intraperitoneally), ciprofloxacin produced comparable dose-dependent SCE frequency increases. Ciprofloxacin was postulated to be specific for the target DNA gyrase, the prokaryotic homologue of DNA topoisomerase type II enzyme. The present paper along with the existing earlier data strongly suggest that topoisomerase type II and DNA gyrase are physiological targets for the drug action. In view of the present significant in vivo mammalian DNA topoisomerase type II-mediated genotoxicity and clastogenicity data, ciprofloxacin should be administered with caution.
Mukherjee
A
A
Department of Botany, University of Calcutta, India.
Sen
S
S
Agarwal
K
K
D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D002939:Ciprofloxacin / Q000633:toxicity*; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D005047:Etoposide / Q000633:toxicity; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange
D009153:Mutagens; D002939:Ciprofloxacin; D005047:Etoposide; D004250:DNA Topoisomerases, Type II