No cytogenetic effects of quinolone treatment in humans

Abstract

Cytogenetic effects of ciprofloxacin (500 to 2,000 mg daily) and ofloxacin (200 mg daily) were studied in lymphocytes from 31 patients treated for 1 to 10 weeks. Blood samples for cytogenetic analysis were taken before the start of treatment from all patients, after 1 week from 25 patients, and after 2, 4, 6, and 10 weeks from six patients. No chromosome-damaging effect could be demonstrated in any treatment group. The mean aberration yields for each cytogenetic parameter studied and the total number of aberrations were all normal at each sampling occasion.Ciprofloxacin, norfloxacin, and ofloxacin are new quinolone derivatives which are structurally related to nalidixic acid but far more bactericidal; they are active against a wide range of gram-positive and gram-negative bacteria. The new 4-quinolones bind to DNA (9) Blood samples for cytogenetic analysis were taken before the start of treatment from all patients, after 1 week of treatment from the first group, and after 2, 4, 6, and 10 weeks of treatment from the second group.The blood samples were cultured for 48 h at 37°C in 10 ml of McCoy 5A medium with 20% fetal calf serum according to a standard method. Chromosome preparations were stained with Giemsa stain. One hundred metaphases from each individual and sampling occasion were analyzed on coded slides by two investigators, and the aberrations were recorded according to the ISCN nomenclature system (7). When difficulty arose in the classification of an aberration, a second opinion was sought. Such cells were never rejected, and agreement between the two observers was required

Toxicity of quinolone antimicrobial agents

“…These findings suggest the possibility that these new quinolones may induce genotoxic effects in humans. In clinical experience, however, ciprofloxacin and ofloxacin have failed to induce chromosomal aberrations in peripheral lymphocytes in Phase I volunteers and patients (Shimada et al, 1984;Mitelman et al, 1988). Results from the in vitro and in vivo cytogenetic studies suggest that the potency of these drugs in the induction of chromosomal aberrations may in part be due to the affinity of each quinolone for topoisomerase II.…”

Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems

“…There is currently a good deal of debate in the literature concerning the interpretation of positive in vitro genotoxicity results observed in a single test system, because of the finding that quinolones do not induce the same responses in in vivo tests (9,36,39). McQueen and Williams (36) found that norfloxacin, ofloxacin, pefloxacin, and ciprofloxacin induced DNA breakage and repair in the in vitro rat hepatocyte assay at levels between 300 and 500 p,g/ml.…”

Activity of quinolones in the Ames Salmonella TA102 mutagenicity test and other bacterial genotoxicity assays

“…Quinolones have been reported to affect eukaryotic cells in vitro by inducing unscheduled DNA synthesis, DNA strand breakage, inhibition of cell growth, and inhibition of immunoglobulin secretion in human lymphocytes (2,6,13,23). The in vivo effects of quinolones on eukaryotic cells are not as well documented and are usually negative (21,23). However, abnormal bone marrow cells were observed for mice given five daily parenteral doses of the quinolone CP-67,015 at 500 mg/kg of body weight per day (11).…”