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  -