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  • 1. Ali, Imran
    et al.
    Hurmerinta, Teija
    Nurmi, Tarja
    Berglund, Marika
    Rüegg, Joelle
    Poutanen, Matti
    Halldin, Krister
    Mäkelä, Sari
    Damdimopoulou, Pauliina
    From pure compounds to complex exposure: Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo.2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 253Article in journal (Refereed)
    Abstract [en]

    Exposure to environmental endocrine active compounds correlates with altered susceptibility to disease in human populations. Chemical risk assessment is single compound based, although exposure often takes place as heterogeneous mixtures of man-made and natural substances within complex matrices like diet. Here we studied whether the effects of cadmium and enterolactone on endocrine endpoints in dietary exposure can be predicted based on pure compound effects. Ovariectomized estrogen reporter ERE-luciferase (ERE-luc) mice were maintained on diets that intrinsically contain increasing concentrations of cadmium and enterolactone precursors for three and 21 days. The activation of the ERE-luc, epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK)-ERK1/2, and classical estrogen responses were measured. Interactions between the diets and endogenous hormone were evaluated by challenging the animals with 17β-estradiol. Compared to animals on basal purified diet, mice consuming experimental diets were exposed to significantly higher levels of cadmium and enterolactone, yet the exposure remained comparable to typical human dietary intake. Surprisingly, we could not detect effects on endpoints regulated by pure enterolactone, such as ERE-luc activation. However, cadmium accumulation in the liver was accompanied with activation of EGFR and MAPK-ERK1/2 in line with our earlier CdCl2 studies. Further, attenuation of 17β-estradiol-induced ERE-luc response in liver by experimental diets was observed. Our findings indicate that the exposure context can have substantial effects on the activity of endocrine active compounds in vivo. Thus, whenever possible, a context that mimics human exposure should be tested along with pure compounds.

  • 2. Alvarez-Lloret, Pedro
    et al.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Nyberg, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Rodríguez-Navarro, Alejandro B
    Effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126) on vertebral bone mineralization and on thyroxin and vitamin D levels in Sprague-Dawley rats2009In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 187, no 2, p. 63-68Article in journal (Refereed)
    Abstract [en]

    The aim of the present study is to use Fourier transform infrared spectrometry (FTIR), and transmission electron microscopy (TEM) techniques, to make a more detailed description of toxic effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126) on bone tissue at the microstructural and at the molecular level as a result of an altered bone metabolism. We have analysed potential changes on vitamin D and thyroxin serum levels since these hormones represent endocrine endpoints that are critical for bone growth and development. For this purpose Sprague-Dawley rats were exposed (n=10) to PCB126 (i.p.) for 3 months (total dose, 384microg/kg bodyweight), while control rats (n=10) were injected with corn oil (vehicle). Results from FTIR showed that vertebrae from the exposed rats had an overall lower degree of mineralization (-8.5%; p<0.05) compared with the controls. In addition, results from peripheral quantitative computed tomography (pQCT) analyses showed significant increases in the trabecular bone mineral density (+12%; p<0.05) in the exposed group compared with the controls. The TEM analyses also showed an alteration in the crystallinity properties of vertebral bone mineral with a significant decrease in the size and crystallinity of apatite crystal forming the bone tissue in the exposed vs. non-exposed rats. Serum analysis revealed lower levels of thyroid hormones, FT4 (-42%; p<0.005), TT4 (-26%; p<0.005), and vitamin D (-21%; p<0.005) in exposed group compared to control animals. The complementary techniques (TEM and FTIR) used in this study have revealed insights into possible bone mineralization alteration due to PCB126 exposure. The lowering of both the thyroxin and vitamin D serum levels might be an underlying explanation for the observed effects on bone mineralization.

  • 3.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, SE-17176 Stockholm, Sweden.
    Banack, Sandra
    Inst Ethnomed, POB 3464, Jackson, WY 83001 USA.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, p. 108-114Article in journal (Refereed)
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 4.
    Andersson, Patrik
    et al.
    AstraZeneca R&D, Mölndal, Sweden.
    Kenne, Kerstin
    AstraZeneca R&D, Södertälje, Sweden.
    Glinghammar, Björn
    AstraZeneca R&D, Södertälje, Sweden.
    Pointon, Amy V.
    Global Safety Assessment AstraZeneca, Macclesfield, United Kingdom.
    Åkerblad, Peter
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Lutz, Mareike
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Hovdal, Daniel
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Maxvall, Ingela
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Lindstedt, Eva-Lotte
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Toxicity with LXR agonists – Problem solving activities for mechanistic understanding2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Suppl. (S), p. S39-S39Article in journal (Refereed)
    Abstract [en]

    Several lines of evidence points toward the potential positive effects of LXR (Liver X Receptor) modulators for effective and safe therapy of cardiovascular diseases (CVDs). LXR is a dimeric nuclear hormone receptor that exists as a combination of RXR and one of two subtypes LXR alpha or beta, which act as cholesterol sensors. LXR alpha is highly expressed in the liver, intestine and adipose tissue while LXR beta is ubiquitously expressed. Activation of LXR up-regulates several genes involved in reverse cholesterol transport (RCT), including ABC transporters. This results in increased efflux of cholesterol from macrophages in atherosclerotic vascular lesions to the circulation and further on to other tissues to ultimately be excreted into the faeces. These effects together with systemic and local anti-inflammatory properties of LXR modulation are likely to contribute to decreased atherosclerosis. The positive effects of LXR activation on RCT and cholesterol balance must be obtained without negative lipid effects, since LXR also activates lipogenic genes. Other types of toxicity and approaches to better understand the mechanism(s) behind these will be presented. Copyright © 2012 Published by Elsevier Ireland Ltd.

  • 5.
    Andrén, Per E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Shariatgorji, Mohammadreza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Goodwin, Richard
    AstraZeneca, Drug Safety & Metab, Cambridge, England..
    Investigating drug-induced toxicity in tissue samples using mass spectrometry imaging2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, no S, p. S42-S42Article in journal (Other academic)
  • 6. Aspenstrom-Fagerlund, Bitte
    et al.
    Tallkvist, Jonas
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Glynn, Anders W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 237, no 2, p. 133-139Article in journal (Refereed)
    Abstract [en]

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4 g oleic acid/kg b.w. and 1 mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120 min after exposure, or were exposed to 0.6, 2.4 or 4.8 g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90 min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60 min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120 min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  • 7.
    Ax, Erika
    et al.
    Uppsala Univeristy, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupational & Environmental Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Acute & Internal Medicine, Uppsala University, Uppsala, Sweden.
    Lampa, Erik
    Occupational & Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Sjögren, Per
    Clinical Nutrition & Metabolism, Uppsala University, Uppsala, Sweden.
    Circulating levels of environmental contaminants are associated with dietary pattern2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S101-S101Article in journal (Refereed)
  • 8. Batistuzzo, S.
    et al.
    Galvão, M. O.
    Duarte, E. S.
    Hoelzemann, J. J.
    Menezes Filho, J.
    Sadiktsis, Ioannis
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Dreij, K.
    PAH exposure and relationship between buccal micronucleus cytome assay and urinary 1-hydroxypyrene levels among cashew nut roasting workers2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, p. S223-S224Article in journal (Refereed)
    Abstract [en]

    The present study conducted the first assessment of the occupational risk associated to artisanal cashew nut roasting by the use of exposure and effect biomarkers, as well as the characterization and dispersion analysis of the released particulate matter (PM). The PM concentrations in the exposed area were higher than in the non-exposed area. Furthermore, in the control area yielded a higher prevalence of coarse particles, while in the exposed area was observed fine particles. The morphological analysis showed a wide variety of particles. Biomass burning tracers K, Cl, S and Ca were the major inorganic compounds and polycyclic aromatic hydrocarbons (PAHs) with mutagenic and carcinogenic potential, such as benzo[a]pyrene, benzo[b]fluoranthene, benzo[a]anthracene, benzo[j]fluoranthene and indeno[1,2,3-c,d]pyrene were the most abundant PAHs. In addition, atmospheric modeling analysis suggest that these particles can reach regions higher than 40 kilometers. Occupational PAH exposure was confirmed by increases in 1-OHP levels in cashew nut workers. The frequencies of BMCyt biomarkers of genotoxic (micronuclei and nuclear bud) and cytotoxic (pyknosis, karyolysis, karyorrhexis and condensed chromatin) were higher in the exposed group (p < 0.0001) compared with the control group. The influence of factors such as age on the micronucleus was evidenced and a correlation between 1-OHP and MN was observed. It was the first study to found a correlation between these types of biomarkers. The uses of exposure and effect biomarkers were therefore efficient in assessing the occupational risk associated with artisanal cashew nut roasting and the high rates of PM2.5 are considered a potential contributor to this effect.

  • 9.
    Bauden, Monika
    et al.
    Lund University.
    Tassidis, Helena
    Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Research environment Man & Biosphere Health (MABH).
    Ansari, Daniel
    Lund University.
    In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 236, no 1, p. 8-15Article in journal (Refereed)
    Abstract [en]

    Apicidin is a potent histone deacetylase inhibitor (HDACI) that selectively binds to histone deacetylases (HDACs) class I and interferes with the deacetylation process, which results in modification of acetylation level of cellular proteins. The aim of the study was to investigate the potential time and dose dependent cytotoxicity of the test compound, Apicidin, in pancreatic cancer cells Capan-1 and Panc-1 as well as estimate maximal tolerable dose (MTD) of the test agent and determine EC50 using four complementary colorimetric cytotoxicity or viability assays. The cells were treated with increasing concentrations of Apicidin (0-5000nM) for 2, 4 and 6h (short term exposure) or 24, 48 and 72h (long term exposure) before conducting cytotoxic analyses with lactate dehydrogenase assay or viability analyses with sulforhodamine B (SRB), methyl tetrazolium (MTT) and crystal violet (CV) assays. In order to investigate whether Apicidin irreversibly affects the cells already during the short term exposure, the medium containing Apicidin was removed and replaced with fresh culturing medium after 6h of treatment. The cells were then incubated for additional 24, 48 or 72h before carrying out the analysis. The results obtained from cytotoxicity and viability assays indicated, that Apicidin was well tolerated by both cell lines at concentrations below 100nM at any given time point and at all applied concentrations during the short term (6h or less) treatment. Continuous prolonged term exposures (48h or greater) of the cells to Apicidin with concentration exceeding 100nM resulted in significantly increasing cytotoxicity and sustained significant loss of cell viability. Moreover, long term exposure of pancreatic cancer cells Capan-1 and Panc-1 to Apicidin concentrations exceeding 100nM showed an initial anti-proliferative effect before cytotoxicity onset. In summary, MTD was exposure time dependent and estimated to 100nM for long term treatment and to at least 5000nM for treatment not greater than 6h. EC50 concentration of Apicidin was established after long term treatment, however with some variation when comparing the different assays and cell lines. Results from this study may encourage reinvestigating the capacity of potent HDACI Apicidin as an attractive agent for interfering with the deacetylation process catalyzed by HDACs for potential pancreatic cancer intervention.

  • 10.
    Berg, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Müllerian Duct Dysgenesis: a common cause for female reproductive disorders2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no suppl., p. S184-Article in journal (Refereed)
  • 11.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Biomonitoring of metals: Analysis, non-linearity, possible artefacts, and genetics2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S12-S12Article in journal (Refereed)
  • 12. Bergström, Jonas P.
    et al.
    Gry, Marcus
    Lengqvist, Johan
    Lindberg, Johan
    Schwenk, Jochen
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Drobin, Kimi
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Watkins, Paul B.
    Schuppe Koistinen, Ina
    Novel DILI biomarkers for prediction of acetaminophen-induced human hepatotoxicity2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S76-S76Article in journal (Other academic)
  • 13. Beronius, A.
    et al.
    Rudén, Christina
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Hanberg, A.
    Improving the transparency of data evaluation in risk assessment of endocrine disrupting compounds-Implications from the bisphenol A case study2011In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 205, p. S256-S256Article in journal (Other academic)
    Abstract [en]

    The complex biology and toxicology of endocrine disrupting compounds (EDCs) makes toxicity testing as well as evaluation of data for risk assessment difficult. Standardized test guidelines have previously been questioned as to their applicability for evaluating EDC toxicity. However, several guidelines have been updated and enhanced in an effort to better cover EDCs. Also, EDC toxicity is a very active research field and a lot of toxicological data are generated in research studies NOT conducted according to standardized guidelines. Our previous work indicates that differences in how the reliability and relevance of toxicity studies are judged may vary greatly between risk assessments of the same compound and may result in different conclusions about the size and nature of health risks. Further, the process of data evaluation is in many cases in-transparent. The purpose of this on-going study is to contribute to making health risk assessments of EDCs more transparent, systematic, and predictable. The investigation is conducted as a literature study using the EDC bisphenol A (BPA) for a case study. We scrutinize and compare the strengths and weaknesses of both guideline and non-guideline studies evaluating developmental neurotoxicity of BPA. One goal is to further assess the applicability of standardized guidelines in this case. Another aim is to propose improvements in the process of data reporting of non-guideline studies and recommend criteria for the evaluation of data in order to facilitate risk assessment of EDCs.

  • 14.
    Beronius, Anna
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Willighagen, Egon
    Maastricht Univ, Maastricht, Netherlands .
    Rudén, Christina
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Hanberg, Annika
    Karolinska Inst, Stockholm, Sweden.
    Factors influencing developmental neurotoxicity study outcome in the bisphenol A case2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S128-S129Article in journal (Other academic)
  • 15. Bondarenko, Olesja
    et al.
    Torres, Neus Feliu
    Kupferschmidt, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Garcia-Bennett, Alfonso
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Fadeel, Bengt
    Cellular uptake of mesoporous silica particles is governed by activation state of macrophages2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, p. S188-S188Article in journal (Refereed)
  • 16. Borg, Daniel
    et al.
    Bogdanska,, Jasna
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sundström, Maria
    Stockholm University, Faculty of Science, Department of Environmental Chemistry.
    Nobel, Stefan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Håkansson, Helen
    Bergman, Åke
    Stockholm University, Faculty of Science, Department of Environmental Chemistry.
    DePierre, Joseph
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Halldin, Krister
    Bergström, Ulrika
    Perinatal tissue distribution of perfluorooctane sulphonate (PFOS) in mice2009In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 189, no SI, p. S147-S147Article in journal (Refereed)
  • 17.
    Brittebo, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Andersson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Berg, Anna-Lena
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lindquist, Nils Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hanrieder, Jörg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Neurotoxin-induced fibril formation and protein changes in rodents2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Suppl., p. S193-193Article in journal (Other academic)
  • 18.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Developmental exposure to PBDE 209: sex, neuroprotein and neurobehavioural analyses2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no supplement, p. S90-Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardants in polymers products.Newborns and toddlers can be indirectly and directly exposed to PBDEs during a period of critical rapid brain development. The present study was undertaken to investigate neurotoxic effects after neonatal exposure to PBDE 209 on sex differences, cognitive function, neuroproteins and altered susceptibility to toxicants in adults.

     

    3-day-old NMRI mice were exposed to PBDE 209 (2,2´,3,3´,4,4´,5,5´,6,6´-decaBDE at 0, 1.4, 6.0 and 14 µmol/kg bw). At 2 months of age male mice were exposed to paraoxon (0.25 mg/kg bw, every 2nd day for 7 days) and female mice exposed to nicotine (80 µg nicotine base/kg bw). At the age of 2 and 4 months mice were observed for spontaneous behaviour, before and after adult exposure to paraoxon (male) and nicotine (female). Male mice aged 5 and 7 months were observed for memory and learning. Neuroproteins CaMKII, GAP-43, synaptophysin and tau in cerebral cortex and hippocampus from 7-months old male and female mice were analyzed.

     

    The present study shows that neonatal exposure to PBDE 209 can induce developmental neurobehavioural defects in both male and female mice. Neonatal exposure to PBDE 209 also caused increased susceptibility in adult mice to paraoxon and nicotine. All these effects were dose response related. Further, neonatal exposure to PBDE 209 caused persistent defects in memory and learning in adult male mice and increased levels of important neuroproteins e.g. tau in adult male and female mice.

  • 19.
    Carlsson, Lars
    et al.
    AstraZeneca R&D.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Eklund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Boyer, Scott
    AstraZeneca R&D.
    Model building in Bioclipse Decision Support applied to open datasets2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Suppl., p. S62-Article in journal (Refereed)
    Abstract [en]

    Bioclipse Decision Support (DS) is a system capable of building predictive models of any collection of SAR data, and making them available in a simple user interface based on Bioclipse (www.bioclipse.net).

    The method is fast and uses Faulon Signatures as chemical descriptors together with a Support Vector Machine algorithm for QSAR model building. A key feature is the capability to visualize and interpret results by highlighting the substructures which contributed most to the prediction. This, together with very fast predictions, allows for editing chemical structures with instantly updated results.

    We here present the results from applying Bioclipse Decision Support to several open QSAR data sets, including endpoints from OpenTox and PubChem. The results show how to extract data from the sources and to build models which can be integrated with user specific models.

  • 20. Chaudhry, Qasim A.
    et al.
    Hanke, Michael
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Numerical Analysis, NA.
    Study of intracellular reaction and diffusion mechanism of carcinogenic PAHs: Using non-standard compartment modeling approach2013In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 221, p. S182-S182Article in journal (Other academic)
  • 21.
    Cronholm, Pontus
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Karlsson, Hanna L.
    Karolinska Inst, Stockholm, Sweden.
    Hedberg, Jonas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Lowe, Troy
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Elihn, Karine
    Stockholm Univ, Stockholm, Sweden .
    Wallinder, Inger Odnevall
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Möller, Lennart
    Karolinska Inst, Stockholm, Sweden.
    A Trojan Horse type mechanism: Cellular dose and toxicity of Ag and CuO nanoparticles2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S201-S201Article in journal (Other academic)
  • 22. Dach, Katharina
    et al.
    Alm, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Giersiefer, Susanne
    Fritsche, Ellen
    Of mice and men: Mechanistic studies on the developmental neurotoxicity of polybrominated diphenyl ethers (PBDES) in a 3D in vitro model2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, p. S118-S118Article in journal (Other academic)
  • 23.
    Ding, Qian
    et al.
    Philosophy and History, KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Malkiewicz, Katarzyna
    Philosophy and History, KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Rudén, Christina
    Philosophy and History, KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Hansson, Sven Ove
    Philosophy and History, KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Are the new Chinese chemicals regulations catching up with REACH?2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169Article in journal (Other academic)
  • 24.
    Ding, Qian
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Schenk, Linda
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Malkiewicz, Katarzyna
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Hansson, Sven Ove
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    A comparison of occupational exposure limits in Asia and Europe2011In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 205, p. S241-S241Article in journal (Other academic)
    Abstract [en]

    Occupational exposure limits (OELs) are used as a risk management tool aiming at protecting against negative health effects due to occupational exposure to harmful substances. The systems of OELs development have not been standardized and the divergent outcomes have been reported. However some harmonization process has been initiated, primary in Europe. This study aims at analysis of the state of harmonization in a more global context. The OELs systems of eight Asian and seventeen European organizations are analyzed with respect to: (1) the information regarding each organization's system for determining OELs; (2) similarity of substance selection in each system; (3) similarity of value levels of OEL. The analysis shows that the majority of investigated organizations declare to be influenced by the American Conference of Governmental Industrial Hygienists (ACGIH) systems, what in many cases is empirically confirmed. The EU harmonization process is also reflected in results showing the trends of convergence within the EU. However, the comparisons of Asian and European organisations indicate that there is no obvious evidence that OELs are becoming globally harmonized.

  • 25.
    Dreij, Kristian
    et al.
    Karolinska Inst, Stockholm, Sweden .
    Chaudhry, Qasim A.
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis, NA.
    Zhang, Jie
    Karolinska Inst, Stockholm, Sweden .
    Sundberg, Kathrin
    Karolinska Inst, Stockholm, Sweden .
    Jernström, Bengt
    Karolinska Inst, Stockholm, Sweden .
    Hanke, Michael
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis, NA.
    Morgenstern, Ralf
    Karolinska Inst, Stockholm, Sweden .
    In silico modeling of the intracellular dynamics of polycyclic aromatic hydrocarbons2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S60-S61Article in journal (Other academic)
  • 26. Dreij, Kristian
    et al.
    Jarvis, Ian
    Bergvall, Christoffer
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Roger, Westerholm
    Stenius, Ulla
    Influence of interactions between polycyclic aromatic hydrocarbons on health effects2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S35-S35Article in journal (Refereed)
  • 27.
    Durling, Louise
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Svensson, Kettil
    Abramsson-Zetterberg, Lilianne
    Furan is not genotoxic in the micronucleus assay in vivo or in vitro2007In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 169, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    Furan, a potential human carcinogen, is formed during heat-treatment of food. Previous studies of the genotoxicity of furan have given disparate results. Hence, there is a need for complementary data to clarify the mechanism behind the carcinogenicity of furan. In this study, we have used the flow cytometer-based micronucleus assay in mice and the cytokinesis-block micronucleus assay in human lymphocytes to investigate the genotoxic potential of furan. Three in vivo experiments were performed: intraperitoneal or subcutaneous injection of furan in male Balb/C mice (0–300 and 0–275 mg/kg body weight, respectively) and intraperitoneal injection of male CBA mice (0 and 225 mg/kg body weight). No increased level of micronucleated erythrocytes was detected in any of the in vivo experiments. In the in vitro setup, human lymphocytes from two donors were treated with furan in concentrations from 0 to 100 mM, either with or without metabolic activation (liver homogenate from rat). In parity with the in vivo results there was no significant increase in the frequency of micronucleated cells here either. As neither the in vivo nor the in vitro studies disclose any significant increase in the micronucleus frequency after treatment with furan, our results support that the carcinogenicity of furan is caused by a non-genotoxic mechanism.

  • 28. Erratico, Claudio
    et al.
    Zheng, Xiaobo
    Rydén, Andreas
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Marsh, Göran
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Maho, Walid
    Covaci, Adrian
    Human hydroxylated metabolites of BDE-47 and BDE-99 are glucuronidated and sulfated in vitro2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 236, no 2, p. 98-109Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) were used worldwide as additive flame retardants and are classified as persistent, bioaccumulable and toxic environmental pollutants. In humans, the hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) formed in vitro have also been detected in vivo. To further characterize the metabolism of BDE-47 and BDE-99 and to identify candidate markers for monitoring the human exposure to PBDEs using non-invasive approaches, glucuronidation and sulfation of hydroxylated metabolites of BDE-47 and BDE-99 were investigated using human liver microsomes and cytoplasm, respectively. The formed Phase II metabolites were analyzed by liquid chromatography-tandem mass spectrometry using a novel approach to develop analytical methods in absence of authentic standards. All available standards for hydroxylated metabolites of BDE-47 and BDE-99 were glucuronidated and sulfated, showing that glucuronidation and sulfation are part of the metabolism pathway of BDE-47 and BDE-99 in vitro. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-47 were (a) 2,4-DBP-Gluc and 5-Gluc-BDE-47, and (b) 2'-Sulf-BDE-28, 4-Sulf-BDE-42 and 3-Sulf-BDE-47, respectively. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-99 were (a) 2,4,5-TBP-Gluc and 6'-Gluc-BDE-99, and (b) 3'-Sulf-BDE-99 and 5'-Sulf-BDE-99, respectively. Apparent K-m values associated with the formation of sulfated metabolites of BDE-47 and BDE-99 were ten times lower than those of the corresponding glucuronidated metabolites, suggesting that sulfated rather than glucuronidated metabolites of OH-PBDEs might be used as markers of human exposure to PBDEs using a non-invasive approach based on urine sample collection.

  • 29.
    Fick, Jerker
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A search for 120 pharmaceuticals in wild fish from five European countries2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S30-Article in journal (Other academic)
  • 30.
    Forsby, Anna
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Norman, Kimberly
    EL Andaloussi-Lilja, Johanna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Lundqvist, Jessica
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Wojcik, Beata
    Walczak, Vincent
    Curren, Rodger
    Martin, Katharine
    Tierney, Neena
    Predicting eye stinging potential of baby shampoos by assessing TRPV1 channel activity2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S113-S113Article in journal (Refereed)
    Abstract [en]

    The Transient Receptor Potential Vanilloid type 1 (TRPV1) receptor is one of the most well characterized pain-inducing receptors. The purpose of this study was to predict human eye stinging of 19 baby bath and shampoo formulations by studying TRPV1 activity. The NociOcular test, a novel recombinant neuronal in vitro model with high expression of functional TRPV1 channels was used to test shampoo formulations containing surfactants, preservatives, and fragrances (sodium laureth sulfate, cocoamidopropylbetaine, cocoglucoside, sodium benzoate, quaternium-15, etc.). The increase in intracellular free Ca2+ was analysed by fluorescence during exposure. TRPV1-specific Ca2+ influx was abolished when the TRPV1 channel antagonist capsazepine was applied to the cells prior to shampoo samples. The positive control, i.e. adult shampoo, was the most active sample tested in the NociOcular test and also induced the worst stinging sensation. The negative control, i.e. marketed baby shampoo, was negative in both tests. Seven of the formulations induced stinging in the human test, and of those six were positive in the NociOcular test. Twelve of the formulations were classified as non-stinging in the human test, and of those 10 were negative in the NociOcular test. None of the established in vitro tests for eye irritation were able to correctly predict the human stinging sensation of the baby products. Our data support that the TRPV1 channel is a principle mediator of eye stinging sensation induced by baby bath and shampoo formulations and that the NociOcular test may be a valuable in vitro tool to predict human eye stinging sensation.

  • 31.
    Gunnarsson, David
    et al.
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Nordberg, Gunnar
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Selstam, Gunnar
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Differential effects of cadmium on the gene expression of seven-transmembrane-spanning receptors and GAPDH in the rat testis.2007In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 168, no 1, p. 51-7Article in journal (Refereed)
    Abstract [en]

    Cadmium (Cd) is a widely spread toxicant with endocrine disrupting properties. Under experimental conditions it suppresses sex steroid synthesis in the male as well as the female. Testicular steroidogenesis is primarily regulated by gonadotropins, but is also influenced by catecholamines. We have previously shown that Cd exposure affects rat testosterone synthesis by down-regulating luteinizing hormone (LH) receptor mRNA expression. In this study, rats were given 10 micromol/kg Cd subcutaneously and sacrificed 0.48-144 h later. We investigated the effects of Cd on testicular gene expression of two adrenergic receptors. In addition, mRNA levels of the androgen-regulated house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured. In contrast to the suppressive influence on LH receptor expression Cd lacked effect on the expression of alpha(1A)- and beta(2)-adrenergic receptors. GAPDH gene expression, on the other hand, was up-regulated 1.6-fold after exposure to 10 micromol/kg Cd. These data suggest that the influence of Cd on testicular gene expression involves a specific effect on the LH receptor and not a general effect on seven-transmembrane-spanning receptors. Also, data indicate that the increased expression of GAPDH may be secondary to Cd-induced testosterone deprivation, suggesting future studies of androgen-regulated genes in the toxicity of Cd.

  • 32. Gutleb, Arno C.
    et al.
    Arvidsson, Dan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Skaare, Janneche Utne
    Aleksandersen, Mona
    Ropstad, Erik
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Effects on bone tissue in ewes (Ovies aries) and their foetuses exposed to PCB 118 and PCB 1532010In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 192, no 2, p. 126-133Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate whether low levels of mono-ortho PCB 118 and di-ortho PCB 153, affect bone composition and strength in ewes (Dala breed) and their foetuses following exposure starting at conception and ending a week before expected delivery. In male foetuses, trabecular bone mineral content at the metaphysis was almost 30% lower in the PCB 118 (49mug/kg body wt/day) group compared to the control group (corn oil) (ANCOVA, P<0.05). In female foetuses of the PCB 153 (98mug/kg body wt/day) group trabecular cross-sectional area at the metaphysis was 19% smaller than in the controls (ANCOVA, P<0.05). At the diaphysis a smaller marrow cavity area (up to 24% reduction) was observed in female and male foetuses exposed to PCB 153 compared with controls (ANCOVA, P<0.05). There were also significant differences at the mid diaphyseal measure point between the PCB 153 and the control group females (ANCOVA, P<0.05). Cortical and total bone mineral density, cortical thickness were significantly higher, endosteal circumference shorter and marrow cavity significantly smaller in the PCB 153 group (ANCOVA, P<0.05). In conclusion there were gender dependent effects on bone tissue and cortical bone was more affected than trabecular bone.

  • 33.
    Haglund, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Åleskog, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Håkansson, Lena Douhan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Jacobsson, Stefan
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lindhagen, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    The FMCA-GM assays, high throughput non-clonogenic alternatives to CFU-GM in preclinical hematotoxicity testing2010In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 194, no 3, p. 102-107Article in journal (Refereed)
    Abstract [en]

    One of the most common dose limiting adverse effects in cancer treatment is myelotoxicity. The aim of this study was to develop an in vitro method for measuring potential myelotoxic properties of a drug candidate in a high throughput setting. Human CD34+ progenitor cells from umbilical cord blood were plated in 384-well microplates with drugs in liquid culture, supplemented with specific cytokines for the granulocytopoietic-macrophage lineage. After 7 or 14 days of proliferation and differentiation the cells were analyzed using the automated non-clonogenic fluorometric microculture cytotoxicity assay (FMCA). Two types of assays setups were evaluated, the FMCA-GM7 where cells were exposed to drugs directly after thawing and cytotoxicity measured on day 7 in contrast to the FMCA-GM14 where the cells were cultured 7 days prior to plating and drug exposure, with viability analysis on day 14 of differentiation. Drug sensitivity was similar in both assays and method validation was performed using 24 drugs with known myelotoxic profile (acyclovir, bortezomib, busulfan, carboplatin, chloramphenicol, chlorpromazine, cisplatin, cytarabine, clozapine, doxorubicin, erlotinib, etoposide, 5-fluorouracil, fludarabine, gefitinib, gemcitabine, hydroxyurea, imatinib, lomustine, melphalan, sorafenib, sunitinib, taxol and 6-thioguanine). The 50% inhibitory concentrations (IC50) from the FMCA-GM7 and the FMCA-GM14 correlated highly (r = 0.83) and (r = 0.82), respectively, with IC50 from the established clonogenic assay (CFU-GM), obtained from the literature. The current data suggests that the FMCA-GM could offer a simple and robust alternative to the CFU-GM assay in preclinical hematotoxicity studies.

  • 34. Hedberg, Jesper
    et al.
    Neiman, Maja
    KTH, School of Biotechnology (BIO), Proteomics.
    Donnes, Pierre
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Molecular profiling of human kidney injury using antibody suspension bead arrays2009In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 189, p. S94-S94Article in journal (Other academic)
  • 35.
    Hedberg, Yolanda
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Stockmann-Juvala, Helene Helene
    Finnish Inst Occupat Hlth, Helsinki, Finland .
    Zitting, Antti
    Finnish Inst Occupat Hlth, Helsinki, Finland .
    Santonen, Tiina
    Finnish Inst Occupat Hlth, Helsinki, Finland .
    Odnevall Wallinder, Inger
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Relevance of in vitro studies for in vivo inhalation toxicity of 316L powder2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S125-S125Article in journal (Other academic)
  • 36. Hellgren, Dennis
    et al.
    Wu, Jianyao
    Roos, Robert
    Westerholm, Emma
    Adfeldt-Still, Oliver
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Halldin, Krister
    Håkansson, Helen
    The PCB effect database: a tool for translational research and health risk assessment2013In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 221, no Suppl., p. S229-S229Article in journal (Other academic)
  • 37.
    Henriksson, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Shaposhnikov, Sergey
    Oslo universitet.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Collins, Andrew
    Oslo universitet.
    Study of gene-specific DNA repair in the comet assay with padlock probes and rolling circle amplification2011In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 202, no 2, p. 142-147Article in journal (Refereed)
    Abstract [en]

    We used padlock probes to study the rate of gene specific repair of three genes, OGG1 (8-oxoguanine-DNA glycosylase-1), XPD (xeroderma pigmentosum group D), and HPRT (hypoxanthine-guanine phosphoribosyltransferase) in human lymphocytes, in relation to the repair rate of Alu repeats and total genomic DNA. Padlock probes offer highly specific detection of short target sequences by combining detection by ligation and signal amplification. In this approach only genes in sequences containing strand breaks, which become single-stranded in the tail, are available for hybridisation. Thus the total number of signals from the padlock probes per comet gives a direct measure of the amount of damage (strand-breaks) present and allows the repair process to be monitored. This method could provide insights on the organisation of genomic DNA in the comet tail. Alu repeat containing DNA was repaired rapidly in comparison with total genomic DNA, and the studied genes were generally repaired more rapidly than the Alu repeats.

  • 38. Huuskonen, Sirpa
    et al.
    Heinala, Milla
    Herting, Gunilla
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Odnevall Wallinder, Inger
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Santonen, Tiina
    Human health risk assessment of ferrosilicon alloys under REACH2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S178-S178Article in journal (Other academic)
  • 39. Jarvis, I.W.H.
    et al.
    Bergvall, Christoffer
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Morales, D.A.
    Kummrow, F.
    Umbuzeiro, G.A.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dreij, K.
    Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2 cells2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that occur naturally in complex mixtures. Many of the adverse health effects of PAHs including cancer are linked to the activation of intracellular stress response signaling. This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2 cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and c-Jun. ATF2 was also identified as a sensitive stress responsive protein with activation observed at extract concentrations equivalent to 0.1 nM BP. We show that exposure to low levels of environmental PAH mixtures more strongly activates these signaling pathways compared to BP alone suggesting effects due to interactions. Taken together, this is the first study showing the involvement of MEK4/JNK/AP-1 pathway in regulating the intracellular stress response after exposure to nanomolar levels of PAHs in environmental mixtures.

  • 40.
    Karlsson, Hanna L
    et al.
    Karolinska Institutet, Department of Biosciences and Nutrition at Novum, Unit for Analytical Toxicology, Huddinge, Stockholm, Sweden.
    Ljungman, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindbom, John
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Möller, Lennart
    Karolinska Institutet, Department of Biosciences and Nutrition at Novum, Unit for Analytical Toxicology, Huddinge, Stockholm, Sweden.
    Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway2006In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 165, no 3, p. 203-211Article in journal (Refereed)
    Abstract [en]

    The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire–road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-α after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p < 0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire–road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.

  • 41.
    Karlsson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Jiang, Liying
    Andersson, Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Ilag, Leopold L.
    Brittebo, Eva B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 226, no 1, p. 1-5Article in journal (Refereed)
    Abstract [en]

    The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is not an amino acid that is normally found in proteins. Our previous autoradiographic study of H-3-labeled BMAA in adult mice unexpectedly revealed a tissue distribution similar to that of protein amino acids. The aim of this study was to characterize the distribution of free and protein-bound BMAA in neonatal rat tissues following a short exposure using autoradiographic imaging and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The autoradiographic imaging of C-14-L-BMAA demonstrated a distinct uptake of radioactivity that was retained following acid extraction in tissues with a high rate of cell turnover and/or protein synthesis. The UHPLC-MS/MS analysis conclusively demonstrated a dose-dependent increase of protein-associated BMAA in neonatal rat tissues. The level of protein-associated BMAA in the liver was more than 10 times higher than that in brain regions not fully protected by the blood-brain barrier which may be due to the higher rate of protein synthesis in the liver. In conclusion, this study demonstrated that BMAA was associated with rat proteins suggesting that BMAA may be mis-incorporated into proteins. However, protein-associated BMAA seemed to be cleared over time, as none of the samples from adult rats had any detectable free or protein-associated BMAA.

  • 42. Karlsson, Oskar
    et al.
    Jiang, Liying
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Andersson, Marie
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Brittebo, Eva B.
    Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 226, no 1, p. 1-5Article in journal (Refereed)
    Abstract [en]

    The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is not an amino acid that is normally found in proteins. Our previous autoradiographic study of H-3-labeled BMAA in adult mice unexpectedly revealed a tissue distribution similar to that of protein amino acids. The aim of this study was to characterize the distribution of free and protein-bound BMAA in neonatal rat tissues following a short exposure using autoradiographic imaging and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The autoradiographic imaging of C-14-L-BMAA demonstrated a distinct uptake of radioactivity that was retained following acid extraction in tissues with a high rate of cell turnover and/or protein synthesis. The UHPLC-MS/MS analysis conclusively demonstrated a dose-dependent increase of protein-associated BMAA in neonatal rat tissues. The level of protein-associated BMAA in the liver was more than 10 times higher than that in brain regions not fully protected by the blood-brain barrier which may be due to the higher rate of protein synthesis in the liver. In conclusion, this study demonstrated that BMAA was associated with rat proteins suggesting that BMAA may be mis-incorporated into proteins. However, protein-associated BMAA seemed to be cleared over time, as none of the samples from adult rats had any detectable free or protein-associated BMAA.

  • 43.
    Kippler, Maria
    et al.
    Institute of Environmental Medicine, Division of Metals and health, Karolinska Institutet, Stockholm, Sweden.
    Hoque, A. M. Waheedul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raqib, Rubhana
    Öhrvik, Helena
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Vahter, Marie
    Institute of Environmental Medicine, Division of Metals and health, Karolinska Institutet, Stockholm, Sweden.
    Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus2010In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 192, no 2, p. 162-168Article in journal (Refereed)
    Abstract [en]

    Cadmium (Cd) is a widespread, highly toxic environmental pollutant known to accumulate in human placenta. The aim of the present study was to elucidate to what extent the accumulation of Cd in human placenta interacts with the transport of micronutrients to the fetus. Cd and micronutrients were measured in placenta and umbilical cord blood from 44 non-smoking, rural Bangladeshi women, using ICPMS. Metallothionein (MT) protein expression was determined in placenta using Western blot. Cd in placenta (median 110 microg/kg dry weight, 20 microg/kg wet weight) was positively associated with maternal urinary Cd. It was also positively associated with Cd in umbilical cord blood (median 0.16 microg/kg), but negatively associated with zinc (Zn; median 3mg/kg) in umbilical cord blood. Umbilical cord blood Zn was positively associated with birth anthropometry measures, and the Cd-related impairment of Zn in umbilical cord blood seemed to decrease size at birth. In multivariate analysis, MT protein expression was associated with Cd (positively) in placenta, but not with Zn or copper (Cu) in placenta. In conclusion, the Cd concentrations in placenta were clearly elevated, which seemed to impair Zn transfer to the fetus. Induction of MT explained the placental accumulation of Cd, but not the impairment of Zn transport.

  • 44.
    Kotova, Natalia
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Juren, Tina
    Myohanen, Kirsi
    Cornelius, Michael
    Abramsson-Zetterberg, Lilianne
    Backman, Josefin
    Menzel, Ulrike
    Rydberg, Per
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Kronberg, Leif
    Vahakangas, Kirsi
    Segerback, Dan
    (32)P-HPLC analysis of N1-(2-carboxy-2-hydroxyethyl)deoxyadenosine: A DNA adduct of the acrylamide-derived epoxide glycidamide2011In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 207, no 1, p. 18-24Article in journal (Refereed)
    Abstract [en]

    Acrylamide (AA) is produced in many types of food products cooked or processed at high temperature. AA is metabolized to the epoxide glycidamide (GA), which can bind to deoxyguanosine and deoxyadenosine in DNA. The GA-derived N7-guanine and N3-adenine adducts are the only products which so far have been analysed in vivo. Because of previous excellent experience from analysis of adducts to N1-adenine, the aim of our study was to investigate if the N1-adenine adduct of GA could be used as a biomarker of AA exposure. A (32)P-postlabelling method was developed and tested (a) on DNA modified in vitro with GA, (b) on cells treated with GA and (c) on liver DNA from mice treated with M. The N1-adenine adduct of GA (analysed after conversion to N(6)-GA-deoxyadenosine-5'-monophosphate) was easily detected in DNA reacted with GA and in DNA from cells exposed to GA, but not in DNA from mice treated with AA. The reason for this is currently not clearly understood, but some of the possible contributing factors are discussed. The application of the method in other experimental conditions should be further pursued in order to solve this matter.

  • 45.
    Lampa, Erik
    et al.
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Dept. of Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupt and Environ Med, Uppsala University, Uppsala, Sweden.
    Mixtures of environmental contaminants and the metabolic syndrome2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S35-, article id OS1-2Article in journal (Refereed)
  • 46.
    Landström, Marene
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The role of transforming growth factor beta signalling pathways in tumour biology2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S4-S4Article in journal (Refereed)
  • 47.
    Larsson, Maria
    et al.
    Örebro University, School of Science and Technology.
    Orbe, Dan
    MTM Research Centre, Sweden.
    Engwall, Magnus
    Örebro University, School of Science and Technology.
    Ah receptor activating capacity of polycyclic aromatic hydrocarbon derivatives2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. s127-, article id P16-18Article in journal (Refereed)
  • 48.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Bladin, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rönn, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala Univ, Publ Hlth & Caring Sci, Uppsala, Sweden.
    Lind, monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Waldén, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Adipose tissue and metabolic homeostasis in Fischer F344 rats, exposed to developmental low doses of bisphenol A, are affected in a gender specific and non-monotonic manner2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S253-S253Article in journal (Other academic)
  • 49.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Bisphenol A increases cortisol production by enhancing phosphorylation of CREB in normal human adrenocortical cells2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, p. S243-S243Article in journal (Other academic)
  • 50.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Induction of LINE-1 promoter hypomethylation, a hallmark of tumorigenesis, in normal human adrenocortical cells by Bisphenol A2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, p. S149-S149Article in journal (Other academic)
123 1 - 50 of 126
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