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New quinolones: in vitro effects as a potential source of clinical toxicity

A Forsgren1, A Bredberg, K Riesbeck

  • 1Department of Medical Microbiology, University of Lund, Malmö General Hospital, Sweden.

Reviews of Infectious Diseases
|July 1, 1989
PubMed

Insights

4-Quinolones impact mammalian cells, affecting DNA replication and cell proliferation differently. While some genotoxicity tests may be misleading, these drugs can cause DNA strand breaks and influence immune responses, leading to contradictory cellular effects.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Toxicology

Background:

  • 4-Quinolones are a class of antibiotics with known effects on mammalian cells.
  • Their precise mechanisms of action at the cellular level, especially at varying concentrations, require further elucidation.
  • Observed effects range from DNA replication inhibition to modulation of immune factors.

Purpose of the Study:

  • To investigate the diverse in vitro effects of 4-quinolones on mammalian cellular functions.
  • To clarify the relationship between drug concentration and cellular responses, including proliferation and genotoxicity.
  • To explore the impact of 4-quinolones on immune mediators and potential central nervous system effects.

Main Methods:

  • In vitro assays to assess DNA replication and cell proliferation inhibition.
  • Evaluation of genotoxicity using assays that account for [3H]thymidine uptake.
  • Measurement of immunoglobulin and interleukin-2 (IL-2) production.
  • Analysis of potential interactions with other drugs affecting the central nervous system.

Main Results:

  • Significant inhibition of cell proliferation by ciprofloxacin and norfloxacin at 20 mg/L.
  • Genotoxicity tests may yield false positives due to altered thymidine uptake, not DNA damage.
  • Ciprofloxacin induces DNA strand breaks at >= 10 mg/L, which are repaired without causing mutations.
  • Immunoglobulin production is inhibited, while IL-2 production is increased by 4-quinolones, with hyperinduction at higher concentrations.
  • Potential for adverse central nervous system effects through interaction with theophylline or anti-inflammatory drugs, and risk of crystalluria.

Conclusions:

  • 4-Quinolones exhibit complex and often contradictory effects on mammalian cells in vitro.
  • While direct genotoxicity is limited, DNA strand breaks and altered immune responses are observed.
  • Interactions with other substances may lead to central nervous system adverse effects, and crystalluria is a potential nephropathic risk.

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