@article{MuellerHelmsRohreretal.2020,
  author    = {M{\"u}ller, Anke Katharina and Helms, Ute and Rohrer, Carsten and M{\"o}hler, Monika and Hellwig, Frank and Glei, Michael and Schwerdtle, Tanja and Lorkowski, Stefan and Dawczynski, Christine},
  title     = {Nutrient composition of different hazelnut cultivars grown in Germany},
  series = {Foods},
  volume    = {9},
  journal   = {Foods},
  number    = {11},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2304-8158},
  doi       = {10.3390/foods9111596},
  pages     = {11},
  year      = {2020},
  abstract  = {Hazelnuts are rarely cultivated in Germany, although they are a valuable source for macro- and micronutrients and can thus contribute to a healthy diet. Near the present, 15 varieties were cultivated in Thuringia, Germany, as a pilot study for further research. The aim of our study was to evaluate the micro- and macronutrient composition of representative, randomly mixed samples of the 15 different hazelnut cultivars. Protein, fat, and fiber contents were determined using established methods. Fatty acids, tocopherols, minerals, trace elements, and ultra-trace elements were analyzed using gas chromatography, high-performance liquid chromatography, and inductively coupled plasma triple quadrupole mass-spectrometry, respectively. We found that the different hazelnut varieties contained valuable amounts of fat, protein, dietary fiber, minerals, trace elements, and alpha-tocopherol, however, in different quantities. The variations in nutrient composition were independent of growth conditions, which were identical for all hazelnut varieties. Therefore, each hazelnut cultivar has its specific nutrient profile.},
  language  = {en}
}
@article{FinkeWandtEbertetal.2020,
  author    = {Finke, Hannah and Wandt, Viktoria Klara Veronika and Ebert, Franziska and Guttenberger, Nikolaus and Glabonjat, Ronald A. and Stiboller, Michael and Francesconi, Kevin A. and Raber, Georg and Schwerdtle, Tanja},
  title     = {Toxicological assessment of arsenic-containing phosphatidylcholines in HepG2 cells},
  volume    = {12},
  number    = {7},
  publisher = {Oxford University},
  address   = {Cambridge},
  doi       = {10.1039/d0mt00073f},
  pages     = {1159 -- 1170},
  year      = {2020},
  abstract  = {Arsenolipids include a wide range of organic arsenic species that occur naturally in seafood and thereby contribute to human arsenic exposure. Recently arsenic-containing phosphatidylcholines (AsPCs) were identified in caviar, fish, and algae. In this first toxicological assessment of AsPCs, we investigated the stability of both the oxo- and thioxo-form of an AsPC under experimental conditions, and analyzed cell viability, indicators of genotoxicity and biotransformation in human liver cancer cells (HepG2). Precise toxicity data could not be obtained owing to the low solubility in the cell culture medium of the thioxo-form, and the ease of hydrolysis of the oxo-form, and to a lesser degree the thioxo-form. Hydrolysis resulted amongst others in the respective constituent arsenic-containing fatty acid (AsFA). Incubation of the cells with oxo-AsPC resulted in a toxicity similar to that determined for the hydrolysis product oxo-AsFA alone, and there were no indices for genotoxicity. Furthermore, the oxo-AsPC was readily taken up by the cells resulting in high cellular arsenic concentrations (50 μM incubation: 1112 ± 146 μM As cellular), whereas the thioxo-AsPC was substantially less bioavailable (50 μM incubation: 293 ± 115 μM As cellular). Speciation analysis revealed biotransformation of the AsPCs to a series of AsFAs in the culture medium, and, in the case of the oxo-AsPC, to as yet unidentified arsenic species in cell pellets. The results reveal the difficulty of toxicity studies of AsPCs in vitro, indicate that their toxicity might be largely governed by their arsenic fatty acid content and suggest a multifaceted human metabolism of food derived complex arsenolipids.},
  language  = {en}
}
@article{EbertZiemannWandtetal.2020,
  author    = {Ebert, Franziska and Ziemann, Vanessa and Wandt, Viktoria Klara Veronika and Witt, Barbara and M{\"u}ller, Sandra Marie and Guttenberger, Nikolaus and Bankoglu, Ezgi Eyluel and Stopper, Helga and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon},
  series = {Journal of trace elements in medicine and biology},
  volume    = {61},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier},
  address   = {M{\"u}nchen},
  doi       = {10.1016/j.jtemb.2020.126563},
  year      = {2020},
  abstract  = {Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified.},
  language  = {en}
}
@article{FinkeWinkelbeinerLossowetal.2020,
  author    = {Finke, Hannah and Winkelbeiner, Nicola Lisa and Lossow, Kristina and Hertel, Barbara and Wandt, Viktoria Klara Veronika and Schwarz, Maria and Pohl, Gabriele and Kopp, Johannes Florian and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice},
  series = {Molecular nutrition \& food research},
  volume    = {64},
  journal   = {Molecular nutrition \& food research},
  number    = {16},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.202000325},
  year      = {2020},
  abstract  = {Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass-spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron-related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects.},
  language  = {en}
}
@article{NicolaiWeishauptBaesleretal.2021,
  author    = {Nicolai, Merle Marie and Weishaupt, Ann-Kathrin and Baesler, Jessica and Brinkmann, Vanessa and Wellenberg, Anna and Winkelbeiner, Nicola Lisa and Gremme, Anna and Aschner, Michael and Fritz, Gerhard and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222010905},
  pages     = {16},
  year      = {2021},
  abstract  = {Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.},
  language  = {en}
}
@article{DuyduBasaranAydinetal.2018,
  author    = {Duydu, Yalcin and Basaran, Nursen and Aydin, Sevtap and Ustundag, Aylin and Yalcin, Can {\"O}zg{\"u}r and Anlar, Hatice Gul and Bacanli, Merve and Aydos, Kaan and Atabekoglu, Cem Somer and Golka, Klaus and Ickstadt, Katja and Schwerdtle, Tanja and Werner, Matthias and Meyer, S{\"o}ren and Bolt, Hermann M.},
  title     = {Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions},
  series = {Archives of toxicology : official journal of EUROTOX},
  volume    = {92},
  journal   = {Archives of toxicology : official journal of EUROTOX},
  number    = {10},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-018-2296-7},
  pages     = {3051 -- 3059},
  year      = {2018},
  abstract  = {Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 +/- 17.47 (7.95-106.8) mg B/day and 570.6 +/- 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.},
  language  = {en}
}
@article{RauschBrockmeyerSchwerdtle2020,
  author    = {Rausch, Ann-Kristin and Brockmeyer, Robert and Schwerdtle, Tanja},
  title     = {Development and Validation of a QuEChERS-Based Liquid Chromatography Tandem Mass Spectrometry Multi-Method for the Determination of 38 Native and Modified Mycotoxins in Cereals},
  series = {Journal of Agricultural and Food Chemistry},
  volume    = {68},
  journal   = {Journal of Agricultural and Food Chemistry},
  number    = {16},
  publisher = {ACS Publications},
  address   = {Washington, DC},
  issn      = {0021-8561},
  doi       = {10.1021/acs.jafc.9b07491},
  pages     = {4657 -- 4669},
  year      = {2020},
  abstract  = {Here, a reliable and sensitive method for the determination of 38 (modified) mycotoxins was developed. Using a QuEChERS-based extraction method [acetonitrile/water/formic acid (75:20:5, v/v/v)], followed by two runs of high performance liquid chromatography tandem mass spectrometry with different conditions, relevant mycotoxins in cereals were analyzed. The method was validated according to the performance criteria defined by the European Commission (EC) in Commission Decision no. 657/2002. Limits of quantification ranged from 0.05 to 150 μg/kg. Good linearity (R2 > 0.99), recovery (61-120\%), repeatability (RSDr < 15\%), and reproducibility (RSDR < 20\%) were obtained for most mycotoxins. However, validation results for Alternaria toxins and fumonisins were unsatisfying. Matrix effects (-69 to +59\%) were compensated for using standard addition. Application on reference materials gave correct results while analysis of samples from local retailers revealed contamination, especially with deoxynivalenol, deoxynivalenol-3-glucoside, fumonisins, and zearalenone, in concentrations up to 369, 58, 1002, and 21 μg/kg, respectively.},
  language  = {en}
}
@article{TurriniKroepflJensenetal.2018,
  author    = {Turrini, Nikolaus G. and Kroepfl, Nina and Jensen, Kenneth Bendix and Reiter, Tamara C. and Francesconi, Kevin A. and Schwerdtle, Tanja and Kroutil, Wolfgang and Kuehnelt, Doris},
  title     = {Biosynthesis and isolation of selenoneine from genetically modified fission yeast},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {10},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c8mt00200b},
  pages     = {1532 -- 1538},
  year      = {2018},
  abstract  = {Selenoneine, a naturally occurring form of selenium, is the selenium analogue of ergothioneine, a sulfur species with health relevance not only as a purported antioxidant but likely also beyond. Selenoneine has been speculated to exhibit similar effects. To study selenoneine's health properties as well as its metabolic transformation, the pure compound is required. Chemical synthesis of selenoneine, however, is challenging and biosynthetic approaches have been sought. We herein report the biosynthesis and isolation of selenoneine from genetically modified fission yeast Schizosaccharomyces pombe grown in a medium containing sodium selenate. After cell lysis and extraction with methanol, selenoneine was purified by three consecutive preparative reversed-phase HPLC steps. The product obtained at the mg level was characterised by high resolution mass spectrometry, NMR and HPLC/ICPMS. Biosynthesis was found to be a promising alternative to chemical synthesis, and should be suitable for upscaling to produce higher amounts of this important selenium species in the future.},
  language  = {en}
}
@article{KroepflFrancesconiSchwerdtleetal.2019,
  author    = {Kroepfl, Nina and Francesconi, Kevin A. and Schwerdtle, Tanja and Kuehnelt, Doris},
  title     = {Selenoneine and ergothioneine in human blood cells determined simultaneously by HPLC/ICP-QQQ-MS},
  series = {Journal of Analytical Atomic Spectrometry},
  volume    = {34},
  journal   = {Journal of Analytical Atomic Spectrometry},
  number    = {1},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {0267-9477},
  doi       = {10.1039/c8ja00276b},
  pages     = {127 -- 134},
  year      = {2019},
  abstract  = {The possible relevance to human health of selenoneine and its sulfur-analogue ergothioneine has generated interest in their quantitative determination in biological samples. To gain more insight into the similarities and differences of these two species, a method for their simultaneous quantitative determination in human blood cells using reversed-phase high performance liquid chromatography (RP-HPLC) coupled to inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) is presented. Spectral interferences hampering the determination of sulfur and selenium by ICPMS are overcome by introducing oxygen to the reaction cell. To access selenoneine and ergothioneine in the complex blood matrix, lysis of the cells with cold water followed by cut-off filtration (3000 Da) is performed. Recoveries based on blood cells spiked with selenoneine and ergothioneine were between 80\% and 85\%. The standard deviation of the method was around 0.10 mg S per L for ergothioneine (corresponding to relative standard deviations (RSD) between 10-1\% for ergothioneine concentrations of 1-10 mg S per L) and 0.25 g Se per L for selenoneine (RSDs of 25-2\% for concentrations of 1-10 g Se per L). The method was applied to blood cell samples from three volunteers which showed selenoneine and ergothioneine concentrations in the range of 3.25 to 7.35 g Se per L and 0.86 to 6.44 mg S per L, respectively. The method is expected to be of wide use in future studies investigating the dietary uptake of selenoneine and ergothioneine and their relevance in human health.},
  language  = {en}
}
@article{RuszkiewiczdeMacedoMirandaVizueteetal.2019,
  author    = {Ruszkiewicz, Joanna A. and de Macedo, Gabriel Teixeira and Miranda-Vizuete, Antonio and Bowman, Aaron B. and Bornhorst, Julia and Schwerdtle, Tanja and Antunes Soares, Felix A. and Aschner, Michael},
  title     = {Sex-Specific response of caenorhabditis elegans to Methylmercury Toxicity},
  series = {Neurotoxicity Research},
  volume    = {35},
  journal   = {Neurotoxicity Research},
  number    = {1},
  publisher = {Springer},
  address   = {New York},
  issn      = {1029-8428},
  doi       = {10.1007/s12640-018-9949-4},
  pages     = {208 -- 216},
  year      = {2019},
  abstract  = {Methylmercury (MeHg), an abundant environmental pollutant, has long been known to adversely affect neurodevelopment in both animals and humans. Several reports from epidemiological studies, as well as experimental data indicate sex-specific susceptibility to this neurotoxicant; however, the molecular bases of this process are still not clear. In the present study, we used Caenorhabditis elegans (C. elegans), to investigate sex differences in response to MeHg toxicity during development. Worms at different developmental stage (L1, L4, and adult) were treated with MeHg for 1h. Lethality assays revealed that male worms exhibited significantly higher resistance to MeHg than hermaphrodites, when at L4 stage or adults. However, the number of worms with degenerated neurons was unaffected by MeHg, both in males and hermaphrodites. Lower susceptibility of males was not related to changes in mercury (Hg) accumulation, which was analogous for both wild-type (wt) and male-rich him-8 strain. Total glutathione (GSH) levels decreased upon MeHg in him-8, but not in wt. Moreover, the sex-dependent response of the cytoplasmic thioredoxin system was observedmales exhibited significantly higher expression of thioredoxin TRX-1, and thioredoxin reductase TRXR-1 expression was downregulated upon MeHg treatment only in hermaphrodites. These outcomes indicate that the redox status is an important contributor to sex-specific sensitivity to MeHg in C. elegans.},
  language  = {en}
}
@article{LohrenBornhorstGallaetal.2015,
  author    = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {The blood-cerebrospinal fluid barrier},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {7},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/C5MT00171D},
  pages     = {1420 -- 1430},
  year      = {2015},
  abstract  = {Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.},
  language  = {en}
}
@article{MeyerRaberEbertetal.2015,
  author    = {Meyer, S. and Raber, G. and Ebert, Franziska and Leffers, L. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites},
  series = {Toxicology research},
  volume    = {5},
  journal   = {Toxicology research},
  number    = {4},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2045-4538},
  doi       = {10.1039/c5tx00122f},
  pages     = {1289 -- 1296},
  year      = {2015},
  abstract  = {Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.},
  language  = {en}
}
@article{CroneAschnerSchwerdtleetal.2015,
  author    = {Crone, Barbara and Aschner, Michael A. and Schwerdtle, Tanja and Karst, Uwe and Bornhorst, Julia},
  title     = {Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS},
  series = {Metallomics},
  volume    = {2015},
  journal   = {Metallomics},
  number    = {7},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-591X},
  doi       = {10.1039/c5mt00096c},
  pages     = {1189 -- 1195},
  year      = {2015},
  abstract  = {cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.},
  language  = {en}
}
@article{MeyerSchulzJeibmannetal.2014,
  author    = {Meyer, S{\"o}ren and Schulz, Jacqueline and Jeibmann, Astrid and Taleshi, Mojtaba S. and Ebert, Franziska and Francesconi, Kevin and Schwerdtle, Tanja},
  title     = {Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster},
  series = {Metallomics},
  journal   = {Metallomics},
  editor    = {Schwerdtle, Tanja},
  publisher = {The Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  pages     = {2010 -- 2014},
  year      = {2014},
  abstract  = {Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood.},
  language  = {en}
}
@article{UnterbergLeffersHuebneretal.2014,
  author    = {Unterberg, Marlies and Leffers, Larissa and H{\"u}bner, Florian and Humpf, Hans-Ulrich and Lepikhov, Konstantin and Walter, J{\"o}rn and Ebert, Franziska and Schwerdtle, Tanja},
  title     = {Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics},
  series = {Toxicology Research},
  volume    = {3},
  journal   = {Toxicology Research},
  number    = {6},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2045-4538},
  pages     = {456 -- 464},
  year      = {2014},
  abstract  = {This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.},
  language  = {en}
}
@article{PieperWeheBornhorstetal.2014,
  author    = {Pieper, Imke and Wehe, Christoph A. and Bornhorst, Julia and Ebert, Franziska and Leffers, Larissa and Holtkamp, Michael and H{\"o}seler, Pia and Weber, Till and Mangerich, Aswin and B{\"u}rkle, Alexander and Karst, Uwe and Schwerdtle, Tanja},
  title     = {Mechanisms of Hg species induced toxicity in cultured human astrocytes},
  series = {Metallomics},
  volume    = {2014},
  journal   = {Metallomics},
  number    = {6},
  issn      = {1756-591X},
  doi       = {10.1039/c3mt00337j},
  pages     = {662 -- 671},
  year      = {2014},
  abstract  = {The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity.},
  language  = {en}
}
@article{MeyerMatissekMuelleretal.2014,
  author    = {Meyer, S{\"o}ren and Matissek, M. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of three arsenic-containing hydrocarbons},
  series = {Metallomics},
  volume    = {2014},
  journal   = {Metallomics},
  number    = {6},
  issn      = {1756-591X},
  doi       = {10.1039/c4mt00061g},
  pages     = {1023 -- 1033},
  year      = {2014},
  abstract  = {Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.},
  language  = {en}
}