- 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 withArsenic-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.…
MetadatenAuthor details: | S. M. Müller, Hannah FinkeGND, Franziska EbertORCiDGND, Johannes Florian KoppORCiDGND, Fabian SchumacherORCiDGND, Burkhard KleuserORCiDGND, Kevin A. FrancesconiORCiD, G. Raber, Tanja SchwerdtleORCiDGND |
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DOI: | https://doi.org/10.1007/s00204-018-2194-z |
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ISSN: | 0340-5761 |
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ISSN: | 1432-0738 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29602950 |
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Title of parent work (English): | Archives of toxicology : official journal of EUROTOX |
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Subtitle (English): | effects on gene expression, epigenetics, and biotransformation in HepG2 cells |
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Publisher: | Springer |
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Place of publishing: | Heidelberg |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/03/30 |
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Publication year: | 2018 |
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Release date: | 2021/12/06 |
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Tag: | Arsenic speciation; Arsenic-containing hydrocarbons; Arsenolipids; Gene expression; Global DNA methylation; Metabolism |
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Volume: | 92 |
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Issue: | 5 |
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Number of pages: | 15 |
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First page: | 1751 |
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Last Page: | 1765 |
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Funding institution: | Heinrich-Stockmeyer Foundation; German Research Foundation (DFG)German Research Foundation (DFG) [SCHW903/10 - 1]; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [I2412-B21]; European Regional Development Fund (EFRE)European Union (EU); federal state Brandenburg |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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