@article{UnterbergLeffersHuebneretal.2014, author = {Unterberg, Marlies and Leffers, Larissa and H{\"u}bner, Florian and Humpf, Hans-Ulrich and Lepikhov, Konstantin and Walter, J{\"o}rn and Ebert, Franziska and Schwerdtle, Tanja}, title = {Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics}, series = {Toxicology Research}, volume = {3}, journal = {Toxicology Research}, number = {6}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2045-4538}, pages = {456 -- 464}, year = {2014}, abstract = {This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.}, language = {en} } @misc{UnterbergLeffersHuebneretal.2014, author = {Unterberg, Marlies and Leffers, Larissa and H{\"u}bner, Florian and Humpf, Hans-Ulrich and Lepikhov, Konstantin and Walter, J{\"o}rn and Ebert, Franziska and Schwerdtle, Tanja}, title = {Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-76239}, pages = {456 -- 464}, year = {2014}, abstract = {This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.}, language = {en} } @book{MenzelWehlmannHoenischetal.2009, author = {Menzel, Michael and Wehlmann, Kerstin and H{\"o}nisch, Martin and Bergemann, Susann and M{\"u}cklich, Franziska and Ruge, Jasmin and Sumida, Nanni and Bieder, Anja and Spreewald, Stefanie and Simon, J{\"o}rn and Freese, Anika and Bormann, Janine and Klinge, Henry and B{\"o}hme, Jan-Christoph and Fachini, Marion and Guß, Janine and Sch{\"u}ler, Susanne and Walter, Susanne and Kaden, Sandra and Kalus, Matthias and Berg, Ronald and Pape, Christine}, title = {Freiheit im Mittelalter am Beispiel der Stadt}, editor = {Klose, Dagmar and Ladewig, Marco}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-940793-95-9}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-31417}, publisher = {Universit{\"a}t Potsdam}, pages = {327}, year = {2009}, abstract = {Kircht{\"u}rme und Zunfth{\"a}user, Marktpl{\"a}tze und enge - oft verdreckte - Gassen zeichnen unser modernes Bild der mittelalterlichen Stadt. Dieser „Ort" war Forum und Zentrum des mittelalterlichen Lebens, dessen Vielfalt und Komplexit{\"a}t sich f{\"u}r uns wie durch ein Brennglas beobachten l{\"a}sst. Dieser Band in der Reihe „Perspektiven historischen Denkens" thematisiert die „st{\"a}dtische Freiheit" unter geschichtsdidaktischen Aspekten. Junge Autorinnen und Autoren stellen hierin sch{\"u}lerzentrierte und narrative Lernarrangements vor, die mit quellengest{\"u}tzten Arbeitsmaterialien multiperspektivische Zug{\"a}nge zur Thematik „Freiheit am Beispiel der mittelalterlichen Stadt" (RLP Berlin-Brandenburg) erm{\"o}glichen. Vorweg gestellte Informationstexte gestatten den Lehrerinnen und Lehrern einen leichtverst{\"a}ndlich und fachlich fundierten Einblick in die Thematik und lohten das methodisch-didaktische Potential der Lernarrangements aus. Im sich anschließenden Materialteil k{\"o}nnen Sie als Lehrkraft aus dem breiten Text- und Bildfundus eine f{\"u}r ihren individuellen Unterricht angepasste Auswahl treffen und ihre Sch{\"u}ler f{\"u}r einen kurzweiligen und handlungsorientierten Unterricht begeistern.}, language = {de} }