1. |
- Bredberg, Anders, et al.
(author)
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4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction
- 1989
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In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 211:1, s. 171-180
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Journal article (peer-reviewed)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.
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2. |
- Carlsson, Jan, et al.
(author)
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Catalase inhibition by sulfide and hydrogen peroxide-induced mutagenicity in Salmonella typhimurium strain TA102
- 1988
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In: Mutation research. - : Elsevier. - 0027-5107 .- 1873-135X. ; 202:1, s. 59-64
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Journal article (peer-reviewed)abstract
- The lethal and mutagenic effects of hydrogen peroxide were studied in exponentially growing cultures of Salmonella typhimurium strain TA102. Exposure of the cultures to non-lethal levels of sodium sulfide significantly increased the lethality and mutagenicity of hydrogen peroxide. The catalase activity was decreased in cells exposed to sodium sulfide, but there were no changes in the cellular levels of superoxide dismutase, glutathione reductase, or NADPH-dependent alkyl hydroperoxide reductase. Hydrogen peroxide-induced mutagenesis and killing of S. typhimurium strain TA102 in the presence of sulfide may in part be explained by an inactivation of catalase by sulfide.
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3. |
- Spyrou, Giannis, et al.
(author)
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Dynamics of the thymidine triphosphate pool during the cell cycle of synchronized 3T3 mouse fibroblasts
- 1988
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In: Mutation research. - : Elsevier. - 0027-5107 .- 1873-135X. ; 200:1-2, s. 37-43
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Journal article (peer-reviewed)abstract
- To investigate whether resting cells of 3T3 mouse fibroblasts carry out de novo synthesis of deoxyribonucleoside triphosphates, we determined the turnover of the thymidine triphosphate pool of G0 cells obtained by starvation of cultures for platelet-derived growth factor. These cells were contaminated by less than 1% S-phase cells. In the absence of deoxyribonucleosides in the medium one million G0 cells contained 5 pmole of dTTP with a turnover of 0.09 pmole/min. S-phase cells in comparison contained a 20 times larger dTTP pool with a more than 200-fold faster turnover. Our results suggest that G0 cells carry out a slow but finite de novo synthesis of deoxyribonucleoside triphosphates to satisfy the cells' requirement for DNA repair and mitochondrial DNA synthesis.
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