Abstract：
:Although the tumor-promoting effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs), and related compounds in liver tissue are primarily attributed to the activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear. Liver progenitor (oval) cells have been suggested to constitute a potential target for hepatocarcinogenic chemicals. To better understand AhR-driven pathways, we analyzed the transcriptional program in response to coplanar PCB 126 in contact-inhibited rat liver progenitor WB-F344 cells using high-density microarrays. After 6-h treatment, we identified 145 significantly deregulated genes considered to be direct AhR-dependent target genes. The number of differentially regulated genes increased to 658 and 968 genes after 24 and 72 h, respectively. Gene ontology analysis revealed that these genes were primarily involved in drug and lipid metabolism, cell cycle and growth control, cancer developmental processes, cell-cell communication, and adhesion. Interestingly, the Wnt and TGF-β signaling pathways, both being involved in developmental and tumorigenic processes, belonged to the most affected pathways. AhR- and ARNT-dependent regulation of selected target genes of interest was then confirmed using TCDD as a model AhR agonist, together with pharmacological inhibition of the AhR and by RNA-interference techniques. We demonstrated AhR-dependent regulation of emerging and novel AhR target genes, such as Fst, Areg, Hbegf, Ctgf, Btg2, and Foxq1. Among them, the transcription factor Foxq1, recently suggested to contribute to tumor promotion and/or progression, was found to be regulated at both mRNA and protein levels by AhR/ARNT activation.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Faust D,Vondráček J,Krčmář P,Smerdová L,Procházková J,Hrubá E,Hulinková P,Kaina B,Dietrich C,Machala Mdoi
10.1007/s00204-012-0979-zsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
681-98issue
4eissn
0340-5761issn
1432-0738journal_volume
87pub_type
杂志文章abstract：:As part of a study on cadmium nephrotoxicity, we studied the effect of cadmium chloride (CdCl2) in isolated human renal proximal tubules metabolizing the physiological substrate lactate. Dose-effect experiments showed that 10-500 μM CdCl2 reduced lactate removal, glucose production and the cellular levels of ATP, coen...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-010-0633-6
更新日期：2011-09-01 00:00:00
abstract：:The effects of a single dose of ethanol on the metabolism and toxicity of chloroform administered to rats per os (p.o.), intraperitoneally (i.p.), or by inhalation (inh) at different doses were investigated. Rats that had been given either ethanol (2 g/kg) or vehicle (water) alone at 4 p.m. on the previous day were ch...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050131
更新日期：1994-01-01 00:00:00
abstract：:The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 mumol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00334632
更新日期：1989-01-01 00:00:00
abstract：:The uncertainties that surround the methods used for risk assessment of exposure to carcinogens have been highlighted by a recent document advocating an approach based on the T25 dose (the dose giving a 25% incidence of cancer in an appropriately designed animal experiment). This method relies on derivation of the T25...
journal_title：Archives of toxicology
pub_type：
doi：10.1007/s002040100271
更新日期：2001-11-01 00:00:00
abstract：:The metabolism of 74As-arsenate (As V, 0.4 mg As/kg body weight, IV) in marmoset monkeys (two males and two females) was studied. Unlike all other animal species studied so far, the marmoset was found to be unable to metabolize the arsenate to dimethylarsinic acid. Most of the absorbed arsenate was reduced to arsenite...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00343121
更新日期：1985-06-01 00:00:00
abstract：:Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. T...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0613-9
更新日期：2005-03-01 00:00:00
abstract：:Cyclohexylmethylphosphonofluoridate (cyclosarin) is a highly toxic organophosphate, which was shown to be rather resistant to conventional oxime therapy. To give more insight into the inhibition, reactivation and aging kinetics, human acetyl-(AChE) and butyrylcholinesterase (BChE) were inhibited by cyclosarin (k2 of 7...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050546
更新日期：1998-09-01 00:00:00
abstract：:HCB was detected in all preparations of human placenta, maternal blood, milk, and cord blood. It was confirmed that HCB transferred from mother to fetus through the placenta. A significant linear correlation exists between the HCB concentration in placenta and that in cord blood. Therefore, the placental concentration...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00333426
更新日期：1985-01-01 00:00:00
abstract：:Assay conditions in determining total cytochrome P-450 in four laboratories were compared. Although the determination was derived from the original Omura and Sato method in each laboratory, the four standard protocols differed slightly, resulting in considerable differences in the results. Since the cytochrome P-450 c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00324544
更新日期：1987-01-01 00:00:00
abstract：:Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, inc...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01974690
更新日期：1990-01-01 00:00:00
abstract：:Hibiscus protocatechuic acid (PCA), a phenolic compound found in the dried flowers of Hibiscus sabdariffa L. (Malvaceae), was demonstrated to have an antioxidant effect in vitro and in vivo, and an antitumor property in our previous study. In the present study, we used lipopolysaccharide (LPS, an endotoxin) to induce ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-002-0404-0
更新日期：2003-01-01 00:00:00
abstract：:Targeted therapies against cancer have improved both survival and quality of life of patients. However, metabolic rewiring evokes cellular mechanisms that reduce therapeutic mightiness. Resistant cells generate more glutathione, elicit nuclear factor erythroid 2-related factor 2 (NRF2) activation, and overexpress many...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-020-02838-8
更新日期：2020-08-01 00:00:00
abstract：:Carbon tetrachloride-induced liver injury is a thoroughly studied model for regeneration and fibrosis in rodents. Nevertheless, its pattern of liver fibrosis is frequently misinterpreted as portal type. To clarify this, we show that collagen type IV+ "streets" and α-SMA+ cells accumulate pericentrally and extend to ne...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-017-2040-8
更新日期：2017-11-01 00:00:00
abstract：:The studies presented were designed to investigate the effects of cytochrome P450 inhibition on tetrahydrofuran-induced hepatocellular proliferation in female B6C3F(1) mice. Groups of female B6C3F(1) mice were exposed to dynamic atmospheres containing tetrahydrofuran (THF) concentrations of 0, 5,400 or 15,000 mg/m(3) ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0474-7
更新日期：2003-08-01 00:00:00
abstract：:The US Environmental Protection Agency's ToxCast program has generated toxicity data for thousands of chemicals but does not adequately assess potential neurotoxicity. Networks of neurons grown on microelectrode arrays (MEAs) offer an efficient approach to screen compounds for neuroactivity and distinguish between com...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02636-x
更新日期：2020-02-01 00:00:00
abstract：:Xenobiotic induced liver injury is a leading cause for drug withdrawal and toxicogenomics may help to identify molecular causes. Here we report studies with cultures of human hepatocytes to detect early responses of liver toxicity upon treatment with the hepatotoxin Aroclor 1254. We studied transcript abundance of 302...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0234-1
更新日期：2008-02-01 00:00:00
abstract：:Several studies have explored the negative effects of cigarette smoke on bone healing; however, the complex pathogenesis still remains unclear. One crucial and primary factor determining effective fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSCs) into bone-forming cells. Recently,...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-017-2149-9
更新日期：2018-04-01 00:00:00
abstract：:For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since proh...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1090-9
更新日期：2013-09-01 00:00:00
abstract：:Exposure to particulate matter (PM) has been related to the onset of adverse health effects including lung cancer, but the underlying molecular mechanisms are still under investigation. Epithelial-to-mesenchymal transition (EMT) is regarded as a crucial step in cancer progression. In a previous study, we reported EMT-...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-018-2259-z
更新日期：2018-09-01 00:00:00
abstract：:To investigate the effect of long term hashish use on T-lymphocytes we have measured the incorporation of 14C-thymidine by peripheral blood lymphocytes, unstimulated and stimulated by phytohemagglutinin, as well as the proportion and number of E-rosettes in 12 healthy male chronic users of the drug before and after a ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01891963
更新日期：1978-04-27 00:00:00
abstract：:Tributyltin (TBT) has been shown to disrupt the ability of natural killer (NK) cells to destroy tumor targets in vitro even at exposures of 25 nM for 24 h, but cell viability was not significantly impacted. Thus, evaluation of intracellular molecular events that regulate cell viability in TBT exposed NK cells are of i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0155-4
更新日期：2007-04-01 00:00:00
abstract：:To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the l...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01969922
更新日期：1993-01-01 00:00:00
abstract：:Capillary gas chromatography coupled to mass spectrometry was employed to quantify ethylmorphine in biological fluids and tissues in a death attributed to oral ethylmorphine ingestion. The femoral blood concentration of the drug was 488 ng/ml. Hair analysis revealed the individual's drug abuse pattern, particularly th...
journal_title：Archives of toxicology
pub_type： 信件
doi：10.1007/s002040050057
更新日期：1994-01-01 00:00:00
abstract：:Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0237-y
更新日期：2008-03-01 00:00:00
abstract：:The excretion and biotransformation of [14C] 1,1-dichloroethylene (vinylidene chloride, VDC) after administration of a single oral dose has been investigated in female rats. Seventy-two hours after a dose of 0.5, 5.0, and 50.0 mg/kg, 1.26, 9.70, 16.47%, respectively, are exhaled as unchanged VDC, and 13.64, 11.35, 6.1...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00353707
更新日期：1979-07-11 00:00:00
abstract：:Since teratogenicity testing in mammals is a particular challenge from an animal welfare perspective, there is a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected embryonic vertebrate in vivo model. The p...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02928-7
更新日期：2020-10-27 00:00:00
abstract：:Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0201-x
更新日期：2007-10-01 00:00:00
abstract：:The effects of six iv infusions of an emulsion containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) on the liver and testes were investigated in 40-day-old rats. Groups of five to six animals received the emulsion every other day in doses of 0, 5, 50 or 500 mg DEHP/kg body weight. Liver effects were studied by...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00348313
更新日期：1985-12-01 00:00:00
abstract：:Second order rate constants for the initial reaction of 12 mammalian oxyhemoglobins (Hb) with equimolar phenylhydrazine (PHZ), a compound inducing Heinz body hemolytic anemia, were determined by recording continuous changes in absorbance with time at 577 nm. The rate constants were varied in a range from 43 m-1.s-1 wi...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050161
更新日期：1995-01-01 00:00:00
abstract：:The aim of this study was to investigate the electrophilic tissue burden (ETB) formation, assessed as covalent binding of the ultimate carcinogen benzo( a)pyrene diolepoxide (BaPDE) with cellular proteins, in liver, lung and heart, as well as with haemoglobin (Hb) following repeated exposure to binary mixtures of benz...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0518-z
更新日期：2004-02-01 00:00:00
