| 1. |
- Bredberg, Anders, et al.
(författare)
-
4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction
- 1989
-
Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 211:1, s. 171-180
-
Tidskriftsartikel (refereegranskat)abstract
- 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 μg/ml) for most of the tested 4-Qs, whereas DNA strand breakage in lymphoblastoid cells was evident only for ciprofloxacin (10 μg/ml and upwards), ofloxacin (80 μg/ml) and norfloxacin (160 μg/ml). Ciphrofloxacin induced a significant amount of unscheduled DNA synthesis, but was found to be negative in a shuttle vector plasmid mutation test. Ciprofloxacin (80 μg/ml) did not inhibit enzymes involved in the early steps of pyrimidine biosynthesis. Cell growth was slightly depressed at a concentration of 20 μg/ml, becoming marked at 80 μg/ml. In conculsion, this study seeks to contribute to an improved evaluation of genotoxic screening test data, by focuding attention on the conflicting effects imposed by the 4-Qs on a battery of such tests.
|
|
| 2. |
- Forsgren, Arne, et al.
(författare)
-
New Quinolones : In Vitro Effects as a Potential Source of Clinical Toxicity
- 1989
-
Ingår i: Reviews of Infectious Diseases. - 0162-0886. ; 11, s. 1382-1389
-
Tidskriftsartikel (refereegranskat)abstract
- 4-Quinolones affect mammalian cellular functions in vitro in several ways. High concentrations inhibit DNA replication, but individual genes are perhaps sensitive to lower concentrations of drug. Inhibition of cell proliferation differs widely among 4-quinolones. Ciprofloxacin and norfloxacin are the most antiproliferative, inhibiting cell growth by -30% at 20 mg/L. Genotoxicity tests with 4-quinolones are probably “false-positive” as a result of increased [3H]thymidine uptake that is not related to DNA damage. Ciprofloxacin at ≥ 10 mg/L causes significant strand breaks in DNA, which seemingly are quickly repaired and do not cause mutations or cancer. Production of immunoglobulin is inhibited by ciprofloxacin at a concentration of 5 mg/L, but production of the growth factor interleukin 2 (IL-2) is increased by 4-quinolones at the same concentration and is hyperinduced at higher concentrations. Thus the effects are very contradictory. Increased production of IL-2 may contribute to central nervous system adverse effects. 4-Quinolones in combination with theophylline or antiinflammatory drugs may inhibit γ-aminobutyric acid receptor binding and thereby have adverse effects on the central nervous system. Some 4-quinolones induce crystalluria, which may be nephropathic.
|
|
