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4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction

Bredberg, Anders LU ; Brant, Marta LU ; Riesbeck, Kristian LU orcid ; Azou, Yannick and Forsgren, Arne LU (1989) In Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 211(1). p.171-180
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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
4-Quinolones, DNA repair, DNA synthesis, Gene mutation, Genetic toxicity
in
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
volume
211
issue
1
pages
171 - 180
publisher
Elsevier
external identifiers
  • pmid:2921999
  • scopus:0024586601
ISSN
1879-2871
DOI
10.1016/0027-5107(89)90117-6
language
English
LU publication?
yes
id
7376ff6b-f3dd-4a80-8cf6-d7c0c956f196
date added to LUP
2019-03-27 14:24:07
date last changed
2024-01-01 00:13:48
@article{7376ff6b-f3dd-4a80-8cf6-d7c0c956f196,
  abstract     = {{<p>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 [<sup>3</sup>H]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.</p>}},
  author       = {{Bredberg, Anders and Brant, Marta and Riesbeck, Kristian and Azou, Yannick and Forsgren, Arne}},
  issn         = {{1879-2871}},
  keywords     = {{4-Quinolones; DNA repair; DNA synthesis; Gene mutation; Genetic toxicity}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{171--180}},
  publisher    = {{Elsevier}},
  series       = {{Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis}},
  title        = {{4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction}},
  url          = {{http://dx.doi.org/10.1016/0027-5107(89)90117-6}},
  doi          = {{10.1016/0027-5107(89)90117-6}},
  volume       = {{211}},
  year         = {{1989}},
}