<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids"^^ . "The first part of the present dissertation assesses genotoxic effects of environmental samples\r\n(e.g. sediment, fish blood) from the River Danube and the Tietê River in Brazil. The\r\ngenotoxic potentials of both rivers were determined by means of the comet assay and the\r\nmicronucleus test. The results, regarding the ecological status of the Danube River, reveal an\r\noverall moderate to severe genotoxic potential with a highly differential localization.\r\nRegarding the Tietê River, strong hazard potentials could especially be detected in samples\r\nfrom Billings reservoir, indicating a major impact of discharges of São Paulo. Overall,\r\nhowever, genotoxicity decreases downstream. In situ observations (i.e. the micronucleus test\r\nwith fish erythrocytes) on the River Danube and the Tietê River showed excellent correlation\r\nwith corresponding in vitro tests (i.e. the comet assay and the micronucleus test with RTL-W1\r\ncells) and document the ecological relevance of in vitro studies with sediment extracts.\r\nIn order to extend the usage of the micronucleus test, modified versions were tested. Results\r\ndemonstrated that the micronucleus assay with fixed (liver) tissues and the modified\r\nmicronucleus test with homogenized zebrafish embryos represent valuable tools for the in\r\nvivo identification of the mutagenic potentials of pure substances, environmental samples and\r\nfield locations.\r\nAs a next step, the genotoxic hazard potential of trenbolone, a model androgen, was tested in\r\nvitro in the permanent fish cell line RTL-W1 as well as in primary cell cultures derived from\r\nzebrafish (Danio rerio) embryos after in vivo exposure. Results confirm the conclusion that\r\nthe steroid trenbolone may act as a genotoxic substance. Once the genotoxicity of trenbolone\r\nwas assessed in the micronucleus test and the comet assay in vitro (with RTL-W1 cells) and\r\nin vivo (with zebrafish embryo cell suspensions), the uptake pattern of trenbolone in zebrafish\r\nembryos was investigated in order to assess if the observed genotoxicity is linked to a certain\r\ntissue in the zebrafish embryos. The results demonstrate that trenbolone has easy access to all\r\ntissues of the embryonic and larval stages of zebrafish and thus no masking of genotoxic\r\neffects is expected. Knowing that trenbolone is ubiquitous in the body of the zebrafish\r\nembryo, the question emerges if this substance might have further impact on organisms than\r\nthe genotoxicity observed and the known endocrine effect. Thus, a two generation test with\r\ntrenbolone was performed, which revealed that the major effect was the masculinisation in the\r\nF1 generation. The significant changes in length were the only effects observed, which could\r\nnot exclusively be related to an endocrine effect.\r\nThe last part of this thesis was a validation of a definite fish test (full life-cycle/two\r\ngeneration) with zebrafish. For this end, beside trenbolone, the anti-androgen flutamide and\r\nthe anti-estrogen tamoxifen citrate were tested in multi-generation tests. Currently available\r\nfish screening assays cover only mechanisms of endocrine action related to sexual endocrine\r\ndisrupting chemicals. For substances other than sexual endocrine disruptors, there is no\r\npossibility to apply a tiered testing strategy. In such cases, a fish life-cycle and/or\r\nmultigenerational test, as definitive test, is directly required to eliminate reasonable suspicion\r\nof an endocrine mode of action. Therefore, it is advisable that future studies focus on\r\nharmonization and validation of several elements of the available guidance for fish full lifecycle\r\ntests and 2-generation tests."^^ . "2012" . . . . . . . "Melanie"^^ . "Boettcher"^^ . "Melanie Boettcher"^^ . . . . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (PDF)"^^ . . . "Diss Boettcher.pdf"^^ . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Genotoxicity and endocrine effects –\r\npopulation relevant impacts of steroids (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #13977 \n\nGenotoxicity and endocrine effects – \npopulation relevant impacts of steroids\n\n" . "text/html" . .