4-Quinolone antibiotics: positive genotoxic screening tests despite an apparent lack of mutation induction.

Bredberg A, Brant M, Riesbeck K, Azou Y, Forsgren A.

Department of Medical Microbiology, University of Lund, Malmo, Sweden.

The effects of different 4-quinolone antibiotic derivatives (4-Qs) in a number of short-term tests commonly employed for the evaluation of genetic toxicity were studied. Incorporation of [3H]thymidine into mitogen-stimulated peripheral blood lymphocytes was strongly enhanced at a low concentration (1.56 micrograms/ml) for most of the tested 4-Qs, whereas DNA strand breakage in lymphoblastoid cells was evident only for ciprofloxacin (10 micrograms/ml and upwards), ofloxacin (80 micrograms/ml) and norfloxacin (160 micrograms/ml). Ciprofloxacin induced a significant amount of unscheduled DNA synthesis, but was found to be negative in a shuttle vector plasmid mutation test. Ciprofloxacin (80 micrograms/ml) did not inhibit enzymes involved in the early steps of pyrimidine biosynthesis. Cell growth was slightly depressed at a concentration of 20 micrograms/ml, becoming marked at 80 micrograms/ml. In conclusion, this study seeks to contribute to an improved evaluation of genotoxic screening test data, by focusing attention on the conflicting effects imposed by the 4-Qs on a battery of such tests.

PMID: 2921999 [PubMed - indexed for MEDLINE]