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

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4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction. / Bredberg, Anders; Brant, Marta; Riesbeck, Kristian; Azou, Yannick; Forsgren, Arne.

I: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 211, Nr. 1, 01.01.1989, s. 171-180.

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T1 - 4-quinolone antibiotics

T2 - Positive genotoxic screening tests despite an apparent lack of mutation induction

AU - Bredberg, Anders

AU - Brant, Marta

AU - Riesbeck, Kristian

AU - Azou, Yannick

AU - Forsgren, Arne

PY - 1989/1/1

Y1 - 1989/1/1

N2 - 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.

AB - 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.

KW - 4-Quinolones

KW - DNA repair

KW - DNA synthesis

KW - Gene mutation

KW - Genetic toxicity

U2 - 10.1016/0027-5107(89)90117-6

DO - 10.1016/0027-5107(89)90117-6

M3 - Article

VL - 211

SP - 171

EP - 180

JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

SN - 1879-2871

IS - 1

ER -