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https://www.readbyqxmd.com/read/28916194/induction-of-cytochrome-p450-mrna-in-porcine-primary-hepatocytes-cultured-under-serum-free-conditions-comparison-of-freshly-isolated-cells-and-cryopreserved
#1
Martin Krøyer Rasmussen
Primary hepatocytes are widely used in the study of dynamic events like regulation of gene expression, as they are superior to most cell-lines. However, the culturing of the hepatocytes often results in loss of phenotype, e.g. the expression of the cytochrome p450s (CYP). The present study investigated the impact of serum in the culture medium of porcine primary hepatocytes (PPH) on markers of dedifferentiation as well as the impact on CYP induction. The effects were studied in both freshly isolated primary hepatocytes as well as cryopreserved...
September 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28913580/in-vitro-tools-for-the-toxicological-evaluation-of-sediments-and-dredged-materials-intra-and-inter-laboratory-comparisons-of-chemical-and-bioanalytical-methods
#2
Kathrin Eichbaum, Markus Brinkmann, Leonie Nuesser, Carolin Gembé, Marina Ohlig, Sebastian Buchinger, Georg Reifferscheid, Markus Hecker, John P Giesy, Henner Hollert
The implementation of in vitro bioassays for the screening of dioxin-like compounds (DLCs) into management guidelines of dredged material is of increasing interest to regulators and risk assessors. This study reports on an intra- and inter-laboratory comparison study between four independent laboratories. A bioassay battery consisting of RTL-W1 (7-ethoxy-resorufin-O-deethylase; EROD), H4IIE (micro-EROD), and H4IIE-luc cells was used to assess aryl hydrocarbon receptor-mediated effects of sediments from two major European rivers, differently contaminated with DLCs...
September 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28904176/the-crystal-structure-of-the-ahrr-arnt-heterodimer-reveals-the-structural-basis-of-the-repression-of-ahr-mediated-transcription
#3
Shunya Sakurai, Toshiyuki Shimizu, Umeharu Ohto
2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds (TCDDs) are extraordinarily potent environmental toxic pollutants. Most of the TCDD toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription...
September 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28886471/dna-damage-by-2-3-7-8-tetrachlorodibenzo-p-dioxin-induced-p53-mediated-apoptosis-through-activation-of-cytochrome-p450-aryl-hydrocarbon-receptor
#4
Durgesh Nandini Das, Prashanta Kumar Panda, Niharika Sinha, Subhadip Mukhopadhyay, Prajna Parimita Naik, Sujit K Bhutia
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; polycyclic aromatic hydrocarbon) is a persistent and ubiquitous environmental contaminant that causes a wide variety of deleterious effects. In this study, the DNA damage and apoptotic activity induced by TCDD was examined using in silico and in vitro approaches. In silico study showed that conformational changes and energies involved in the binding of TCDD to cytochrome P450 1B1 (CYP1B1) were crucial for its target proteins. Moreover, activated TCDD had high affinity to bind with aryl hydrocarbon receptor (AhR), with a binding energy of -564...
August 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28880546/transcriptomic-and-functional-analyses-on-the-effects-of-dioxin-on-insulin-secretion-of-pancreatic-islets-and-%C3%AE-cells
#5
Keng Po Lai, Hin Ting Wan, Alice Hoi-Man Ng, Jing Woei Li, Ting-Fung Chan, Chris Kong-Chu Wong
In this study, transcriptomic and Ingenuity Pathway Analysis (IPA) underlined that an ex-vivo TCDD treatment (0.1 nM) stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line (Min-6) validated the stimulatory effects of TCDD (0.1 and 1 nM) on basal-insulin secretion. At 0.1 nM TCDD treatment on Min-6, western blot analysis showed activation of ERK1/2 and decreased expression of pyruvate dehydrogenase kinase (PDK)...
September 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28862800/neurological-and-neurophysiological-findings-in-workers-with-chronic-2-3-7-8-tcdd-intoxication-50-years-after-exposure
#6
Daniela Pelclova, Pavel Urban, Zdenka Fenclova, Stepanka Vlckova, Petr Ridzon, Karel Kupka, Zuzana Meckova, Ondrej Bezdicek, Tomas Navratil, Jan Rosmus, Sergey Zakharov
The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all subjects, and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%...
September 1, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28860601/cdc42-expression-is-altered-by-dioxin-exposure-and-mediated-by-multilevel-regulations-via-ahr-in-human-neuroblastoma-cells
#7
Tuan Xu, Heidi Q Xie, Yunping Li, Yingjie Xia, Yangsheng Chen, Li Xu, Lingyun Wang, Bin Zhao
Emerging evidence has shown that dioxin causes dysregulation of microRNAs (miRs) in a variety of tissues or cells. However, little is known about dioxin effects on neuronal miRs expression. In the present study, 277 differentially expressed miRs were identified by miRs microarray analysis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, at 10(-10) M) treated SK-N-SH neuroblastoma cells. Among them, 53 miRs exhibited changes of more than 0.4-fold. Consistent with the microarray data, we verified the induction effect of TCDD on hsa-miR-608 expression, which is a primate-specific miR associated with brain functions...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860561/short-chain-fatty-acids-enhance-aryl-hydrocarbon-ah-responsiveness-in-mouse-colonocytes-and-caco-2-human-colon-cancer-cells
#8
Un-Ho Jin, Yating Cheng, Hyejin Park, Laurie A Davidson, Evelyn S Callaway, Robert S Chapkin, Arul Jayaraman, Andrew Asante, Clinton Allred, Evelyn A Weaver, Stephen Safe
Aryl hydrocarbon receptor (AhR) ligands are important for gastrointestinal health and play a role in gut inflammation and the induction of T regulatory cells, and the short chain fatty acids (SCFAs) butyrate, propionate and acetate also induce similar protective responses. Initial studies with butyrate demonstrated that this compound significantly increased expression of Ah-responsive genes such as Cyp1a1/CYP1A1 in YAMC mouse colonocytes and Caco-2 human colon cancer cell lines. Butyrate synergistically enhanced AhR ligand-induced Cyp1a1/CYP1A1 in these cells with comparable enhancement being observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and also microbiota-derived AhR ligands tryptamine, indole and 1,4-dihydroxy-2-naphthoic acid (DHNA)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836330/actein-alleviates-2-3-7-8-tetrachlorodibenzo-p-dioxin-mediated-cellular-dysfunction-in-osteoblastic-mc3t3-e1-cells
#9
Eun Mi Choi, Kwang Sik Suh, Woon-Won Jung, So Young Park, Sang Ouk Chin, Sang Youl Rhee, Youngmi Kim Pak, Suk Chon
The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to affect bone metabolism. We evaluated the protective effects of the triterpene glycoside actein from the herb black cohosh against TCDD-induced toxicity in MC3T3-E1 osteoblastic cells. We found that TCDD significantly reduced cell viability and increased apoptosis and autophagy in MC3T3-E1 osteoblastic cells (P < .05). In addition, TCDD treatment resulted in a significant increase in intracellular calcium concentration, mitochondrial membrane potential collapse, reactive oxygen species (ROS) production, and cardiolipin peroxidation, whereas pretreatment with actein significantly mitigated these effects (P < ...
August 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28812142/tcdd-administered-on-activated-carbon-eliminates-bioavailability-and-subsequent-shifts-to-a-key-murine-gut-commensal
#10
Robert D Stedtfeld, J Brett Sallach, Robert B Crawford, Tiffany M Stedtfeld, Maggie R Williams, Hassan Waseem, Cliff T Johnston, Hui Li, Brian J Teppen, Norbert E Kaminski, Stephen A Boyd, James M Tiedje, Syed A Hashsham
Activated carbon (AC) is an increasingly attractive remediation alternative for the sequestration of dioxins at contaminated sites globally. However, the potential for AC to reduce the bioavailability of dioxins in mammals and the residing gut microbiota has received less attention. This question was partially answered in a recent study examining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hallmark toxic responses in mice administered with TCDD sequestered by AC or freely available in corn oil by oral gavage...
August 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28780123/molecular-insights-into-the-role-of-a-distal-f240a-mutation-that-alters-cyp1a1-activity-towards-persistent-organic-pollutants
#11
Veronika Navrátilová, Markéta Paloncýová, Karel Berka, Shintaro Mise, Yuki Haga, Chisato Matsumura, Toshiyuki Sakaki, Hideyuki Inui, Michal Otyepka
BACKGROUND: Cytochromes P450 are major drug-metabolizing enzymes involved in the biotransformation of diverse xenobiotics and endogenous chemicals. Persistent organic pollutants (POPs) are toxic hydrophobic compounds that cause serious environmental problems because of their poor degradability. This calls for rational design of enzymes capable of catalyzing their biotransformation. Cytochrome P450 1A1 isoforms catalyze the biotransformation of some POPs, and constitute good starting points for the design of biocatalysts with tailored substrate specificity...
August 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28774668/chronic-exposure-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-induces-an-obesogenic-effect-in-c57bl-6j-mice-fed-a-high-fat-diet
#12
Axelle Brulport, Ludovic Le Corre, Marie-Christine Chagnon
Contaminant involvement in the pathophysiology of obesity is widely recognized. It has been shown that low dose and chronic exposure to endocrine disruptor compounds (EDCs) potentiated diet- induced obesity. High and acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant (POP) and an EDC with anti-estrogenic property, causes wasting syndrome . However at lower doses, the TCDD metabolic effects remain poorly understood. We investigated the obesogenic effect during chronic exposure of TCDD at 1μg/kg body weight (bw)/week in adult C57BL/6J mice fed with a high fat diet (HFD) and exposed from 10 to 42 weeks old to TCDD or equal volume of vehicle by intragastric gavage...
August 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28725001/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-elicited-effects-on-bile-acid-homeostasis-alterations-in-biosynthesis-enterohepatic-circulation-and-microbial-metabolism
#13
Kelly A Fader, Rance Nault, Chen Zhang, Kazuyoshi Kumagai, Jack R Harkema, Timothy R Zacharewski
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715762/adsorption-behavior-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-on-pristine-and-doped-black-phosphorene-a-dft-study
#14
Hong-Ping Zhang, Jia-Liang Hou, Yaobin Wang, Ping-Ping Tang, Ya-Ping Zhang, Xiao-Yan Lin, Changsheng Liu, Youhong Tang
Polychlorinated dibenzo-p-dioxins (PCDDs) are highly toxic to humans. The search for novel and effective methods and materials for detecting or removing these gas pollutants is becoming more important and urgent. With its high specific surface area, abundance, and variety of potential applications, phosphorene has attracted much research interest. In this study, density functional theory was used to study the interactions between a doped phosphorene sheet and a tetrachlorodibenzo-p-dioxin (TCDD) molecule. The initial configurations of the TCDD and metallic (Ca or Ti) or nonmetallic (S and Se) dopants were investigated during the TCDD-phosphorene interaction study...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28715759/do-pcdd-pcdf-standard-solutions-used-in-dioxin-analysis-pose-a-risk-as-potentially-acutely-toxic-to-lab-personnel
#15
REVIEW
Rainer Malisch, Michael S Denison, Heidelore Fiedler, Peter Fürst, Ron L A P Hoogenboom, Alexander Schaechtele, Dieter Schrenk, Martin van den Berg
Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential risks were evaluated to determine whether supervision of their use is necessary. Based on LD50-data for oral or dermal intake, hazard classification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a substance (category 1) and in commercially available TCDD standard solutions (category 4) is different...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28699682/2-3-7-8-tetrachlorodibenzo-p-dioxin-promotes-endothelial-cell-apoptosis-through-activation-of-ep3-p38mapk-bcl-2-pathway
#16
Yu Yu, Qian Liu, Shumin Guo, Qianqian Zhang, Juan Tang, Guizhu Liu, Deping Kong, Juanjuan Li, Shuai Yan, Ruiguo Wang, Peilong Wang, Xiaoou Su, Ying Yu
Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to different doses of TCDD, and cell apoptosis was examined...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28696214/epigenetic-regulation-by-agonist-specific-aryl-hydrocarbon-receptor-recruitment-of-metastasis-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#17
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA)...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28681081/genome-wide-mapping-and-analysis-of-aryl-hydrocarbon-receptor-ahr-and-aryl-hydrocarbon-receptor-repressor-ahrr-binding-sites-in-human-breast-cancer-cells
#18
Sunny Y Yang, Shaimaa Ahmed, Somisetty V Satheesh, Jason Matthews
The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24 h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq)...
July 5, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28680151/synergistic-cellular-effects-including-mitochondrial-destabilization-autophagy-and-apoptosis-following-low-level-exposure-to-a-mixture-of-lipophilic-persistent-organic-pollutants
#19
Nathan E Rainey, Ana Saric, Alexandre Leberre, Etienne Dewailly, Christian Slomianny, Guillaume Vial, Harold I Zeliger, Patrice X Petit
Humans are exposed to multiple exogenous environmental pollutants. Many of these compounds are parts of mixtures that can exacerbate harmful effects of the individual mixture components. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is primarily produced via industrial processes including incineration and the manufacture of herbicides. Both endosulfan and TCDD are persistent organic pollutants which elicit cytotoxic effects by inducing reactive oxygen species generation. Sublethal concentrations of mixtures of TCDD and endosulfan increase oxidative stress, as well as mitochondrial homeostasis disruption, which is preceded by a calcium rise and, in fine, induce cell death...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673561/tcdd-induced-mitochondrial-superoxide-production-does-not-lead-to-mitochondrial-degeneration-or-genomic-instability-in-human-sh-sy5y-neuroblastoma-cells
#20
Jukka Luukkonen, Anne Höytö, Matti Viluksela, Jukka Juutilainen, Jonne Naarala
Several genotoxic and non-genotoxic agents have been reported to cause delayed genetic damage in the progeny of the exposed cells. Such induced genomic instability (IGI) may be a driving force in carcinogenesis, and it is thus highly important to understand the cellular events accompanying it. The aim of this study was to investigate whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects mitochondrial integrity and can consequently induce genomic instability. Mitochondrial integrity was evaluated by measuring mitochondrial superoxide production, mitochondrial membrane potential, and mitochondrial activity...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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