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  - Müller, S. M.
A1  - Finke, Hannah
A1  - Ebert, Franziska
A1  - Kopp, Johannes Florian
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Francesconi, Kevin A.
A1  - Raber, G.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons
BT  - effects on gene expression, epigenetics, and biotransformation in HepG2 cells
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.
KW  - Arsenolipids
KW  - Gene expression
KW  - Arsenic-containing hydrocarbons
KW  - Global DNA methylation
KW  - Arsenic speciation
KW  - Metabolism
Y1  - 2018
U6  - https://doi.org/10.1007/s00204-018-2194-z
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 5
SP  - 1751
EP  - 1765
PB  - Springer
CY  - Heidelberg
ER  -