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New Quinolones : In Vitro Effects as a Potential Source of Clinical Toxicity

Forsgren, Arne LU ; Bredberg, Anders LU and Riesbeck, Kristian LU orcid (1989) In Reviews of Infectious Diseases 11. p.1382-1389
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... (More)

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.

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author
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type
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publication status
published
subject
in
Reviews of Infectious Diseases
volume
11
pages
1382 - 1389
publisher
Oxford University Press
external identifiers
  • scopus:0024690839
  • pmid:2549607
ISSN
0162-0886
DOI
10.1093/clinids/11.Supplement_5.S1382
language
English
LU publication?
yes
id
190695a6-56f4-4a2d-be44-8809e7f9e559
date added to LUP
2019-03-27 14:13:45
date last changed
2024-01-01 00:12:17
@article{190695a6-56f4-4a2d-be44-8809e7f9e559,
  abstract     = {{<p>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 [<sup>3</sup>H]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.</p>}},
  author       = {{Forsgren, Arne and Bredberg, Anders and Riesbeck, Kristian}},
  issn         = {{0162-0886}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{1382--1389}},
  publisher    = {{Oxford University Press}},
  series       = {{Reviews of Infectious Diseases}},
  title        = {{New Quinolones : In Vitro Effects as a Potential Source of Clinical Toxicity}},
  url          = {{http://dx.doi.org/10.1093/clinids/11.Supplement_5.S1382}},
  doi          = {{10.1093/clinids/11.Supplement_5.S1382}},
  volume       = {{11}},
  year         = {{1989}},
}