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  -