| 1. |
- Bredberg, Anders, et al.
(författare)
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4-quinolone antibiotics : Positive genotoxic screening tests despite an apparent lack of mutation induction
- 1989
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 211:1, s. 171-180
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Tidskriftsartikel (refereegranskat)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. |
- Adami, Hans-Olov, et al.
(författare)
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The aetiology and pathogenesis of human breast cancer
- 1995
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Ingår i: Mutation research. - 0027-5107 .- 1873-135X. ; 333:1-2, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn--and by inference in utero--and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.
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| 5. |
- Brittebo, Eva B
(författare)
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Metabolism-dependent activation and toxicity of chemicals in nasal glands
- 1997
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Ingår i: Mutation research. - 0027-5107 .- 1873-135X. ; 380:1-2, s. 61-75
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Tidskriftsartikel (refereegranskat)abstract
- The mucosae of the nasal passages contain a large amount of glands which express secretory proteins as well as phase I and phase II biotransformation enzymes. In this review the metabolic activation, covalent binding and toxicity of chemicals in the Bowman's glands in the olfactory mucosa, in the sere-mucous glands in the nasal septum and in the lateral nasal glands and maxillary glands around the maxillary sinuses are discussed. Light microscopic autoradiographic studies have demonstrated a selective covalent binding of nasal toxicants and carcinogens such as halogenated hydrocarbons and N-nitrosamines, especially in the Bowman's glands following a single systemic exposure, suggesting a high rate of metabolic activation of chemicals in these glands. Special attention is put on the herbicide dichlobenil which induces necrosis in the olfactory mucosa following a cytochrome-P450-mediated metabolic activation and covalent binding in the Bowman's glands.
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| 6. |
- Carlsson, Jan, et al.
(författare)
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Catalase inhibition by sulfide and hydrogen peroxide-induced mutagenicity in Salmonella typhimurium strain TA102
- 1988
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Ingår i: Mutation research. - : Elsevier. - 0027-5107 .- 1873-135X. ; 202:1, s. 59-64
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Tidskriftsartikel (refereegranskat)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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