TY - JOUR A1 - Ebert, Franziska A1 - Thomann, Marlies A1 - Witt, Barbara A1 - Müller, Sandra Marie A1 - Meyer, Sören A1 - Weber, Till A1 - Christmann, Markus A1 - Schwerdtle, Tanja T1 - Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool JF - Journal of trace elements in medicine and biology N2 - Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21 days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMAv incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1,Lig1, XRCC1,DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation. (C) 2016 Elsevier GmbH. All rights reserved. KW - Thio-dimethylarsinic acid KW - Long-term cellular toxicity KW - qPCR-based gene expression screening KW - GADD45A and GADD45G KW - DNMT1 KW - Cellular damage response Y1 - 2016 U6 - https://doi.org/10.1016/j.jtemb.2016.06.004 SN - 0946-672X VL - 37 SP - 78 EP - 84 PB - Yokohama Publishers CY - Jena ER - TY - JOUR A1 - Ebert, Franziska A1 - Meyer, Sören A1 - Leffers, Larissa A1 - Raber, Georg A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicological characterisation of a thio-arsenosugar-glycerol in human cells JF - Journal of trace elements in medicine and biology N2 - Arsenosugars are water-soluble arsenic species predominant in marine algae and other seafood including mussels and oysters. They typically occur at levels ranging from 2 to 50 mg arsenic/kg dry weight. Most of the arsenosugars contain arsenic as a dimethylarsinoyl group (Me2As(O)-), commonly referred to as the oxo forms, but thio analogues have also been identified in marine organisms and as metabolic products of oxo-arsenosugars. So far, no data regarding toxicity and toxicokinetics of thio-arsenosugars are available. This in vitro-based study indicates that thio-dimethylarsenosugar-glycerol exerts neither pronounced cytotoxicity nor genotoxicity even though this arsenical was bioavailable to human hepatic (HepG2) and urothelial (UROtsa) cells. Experiments with the Caco-2 intestinal barrier model mimicking human absorption indicate for the thio-arsenosugar-glycerol higher intestinal bioavailability as compared to the oxo-arsenosugars. Nevertheless, absorption estimates were much lower in comparison to other arsenicals including arsenite and arsenic-containing hydrocarbons. Arsenic speciation in cell lysates revealed that HepG2 cells are able to metabolise the thio-arsenosugar-glycerol to some extent to dimethylarsinic acid (DMA). These first in vitro data cannot fully exclude risks to human health related to the presence of thio-arsenosugars in food. (C) 2016 Elsevier GmbH. All rights reserved. KW - Arsenic KW - Thio-arsenosugar-glycerol KW - Toxicity KW - Toxicokinetics KW - Genotoxicity KW - Metabolism Y1 - 2016 U6 - https://doi.org/10.1016/j.jtemb.2016.04.013 SN - 0946-672X VL - 38 SP - 150 EP - 156 PB - Springer Publishing Company CY - Jena ER - TY - JOUR A1 - Rosenkranz, Eva A1 - Maywald, Martina A1 - Hilgers, Ralf-Dieter A1 - Brieger, Anne A1 - Clarner, Tim A1 - Kipp, Markus A1 - Pluemaekers, Birgit A1 - Meyer, Sören A1 - Schwerdtle, Tanja A1 - Rink, Lothar T1 - Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration JF - The journal of nutritional biochemistry N2 - The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 mu g/day (0.3 mg/kg body weight) or 30 mu g/day (1.5 mg/kg body weight) on murine experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis with a Th1/Th17 (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished EAE scores in C57BL/6 mice in vivo (P<.05), reduced Th17 ROR gamma T+ cells (P<.05) and significantly increased inducible iTreg cells (P<.05). While Th17 cells decreased systemically, iTreg cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing iTreg cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. (C) 2015 Elsevier Inc. All rights reserved. KW - Zinc KW - Regulatory T cells (Treg) KW - Foxp3 KW - Mixed lymphocyte culture (MLC) KW - Experimental autoimmune encephalomyelitis (EAE) KW - Th17 Y1 - 2016 U6 - https://doi.org/10.1016/j.jnutbio.2015.11.010 SN - 0955-2863 SN - 1873-4847 VL - 29 SP - 116 EP - 123 PB - Elsevier CY - New York ER -