Effect of gyrase inhibitors on some eukaryotic short-term test systems. DNase I in vitro nucleic acid synthesis and DNA repair in primary cultures of chicken embryo and rat cells.
DNase I activity was diminished by ciprofloxacin (CFL), nalidixic acid, norfloxacin, and ofloxacin in a dose-dependent manner, the MIC's (minimal significantly inhibiting concentrations) being 3.2, 2.8, 2.4, and 7.6 micrograms/ml, resp., in phase I-reaction (increase in DNA hyperchromicity) and 21, 20, 55, and 56 micrograms/ml, resp., in phase II-reaction (formation of acid-soluble products). The Line-weaver-Burk plots indicated inhibition by substrate (phase I) and uncompetitive inhibition (phase II). The decrease in scheduled DNA synthesis by CFL showed MIC's of 270, 100, 1000, and 850 micrograms/ml in chicken embryo brain (B) and liver (L) cells and in rat thymic (T) and splenic (S) cells, resp. With regard to ribonucleic acid synthesis, MIC values of 82, 82, 12.5, and 48 micrograms/ml CFL were determined, resp. Within a concentration range of 25-1600 micrograms/ml, no principal differences existed between the 4-quinolones used. In T-cells, DNA repair as induced by X-irradiation or UV-light and determined by nucleoid sedimentation was inhibited by CFL (greater than 100 micrograms/ml). The present results demonstrate biological effects of 4-quinolones on eukaryotic systems at remarkably low concentrations. In this context, the possibility of interactions with DNA catabolizing enzyme systems and synergistic effects with DNA/chromatin-damaging agents should be considered further.
Tempel
K
K
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Fed. Rep. of Germany.
Ignatius
A
A
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000096:biosynthesis* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D059005:Topoisomerase II Inhibitors; D014466:Ultraviolet Rays; D014965:X-Rays
D059005:Topoisomerase II Inhibitors; D012313:RNA; D004247:DNA; D003850:Deoxyribonuclease I