4-Quinolone antibiotics: positive genotoxic screening tests despite an apparent lack of mutation induction.
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.
Bredberg
A
A
Department of Medical Microbiology, University of Lund, Malmö, Sweden.
Brant
M
M
Riesbeck
K
K
Azou
Y
Y
Forsgren
A
A
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000890:Anti-Infective Agents / Q000633:toxicity*; D002460:Cell Line; D002939:Ciprofloxacin / Q000633:toxicity; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D006131:Growth Inhibitors / Q000633:toxicity; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D006131:Growth Inhibitors; D011742:Pyrimidine Nucleotides; D002939:Ciprofloxacin; D013936:Thymidine