Abstract:
:Genome-wide, promoter-focused ChIP-chip analysis of hepatic aryl hydrocarbon receptor (AHR) binding sites was conducted in 8-week old female C57BL/6 treated with 30 μg/kg/body weight 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2 h and 24 h. These studies identified 1642 and 508 AHR-bound regions at 2h and 24h, respectively. A total of 430 AHR-bound regions were common between the two time points, corresponding to 403 unique genes. Comparison with previous AHR ChIP-chip studies in mouse hepatoma cells revealed that only 62 of the putative target genes overlapped with the 2 h AHR-bound regions in vivo. Transcription factor binding site analysis revealed an over-representation of aryl hydrocarbon response elements (AHREs) in AHR-bound regions with 53% (2 h) and 68% (24 h) of them containing at least one AHRE. In addition to AHREs, E2f-Myc activator motifs previously implicated in AHR function, as well as a number of other motifs, including Sp1, nuclear receptor subfamily 2 factor, and early growth response factor motifs were also identified. Expression microarray studies identified 133 unique genes differentially regulated after 4 h treatment with TCDD. Of which, 39 were identified as AHR-bound genes at 2 h. Ingenuity Pathway Analysis on the 39 AHR-bound TCDD responsive genes identified potential perturbation in biological processes such as lipid metabolism, drug metabolism, and endocrine system development as a result of TCDD-mediated AHR activation. Our findings identify direct AHR target genes in vivo, highlight in vitro and in vivo differences in AHR signaling and show that AHR recruitment does not necessarily result in changes in target gene expression.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Lo R,Celius T,Forgacs AL,Dere E,MacPherson L,Harper P,Zacharewski T,Matthews Jdoi
10.1016/j.taap.2011.08.016subject
Has Abstractpub_date
2011-11-15 00:00:00pages
38-47issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(11)00314-0journal_volume
257pub_type
杂志文章abstract::The use of isocyanates in industry has been increasing and, therefore, the potential for human exposure has also increased. Two such isocyanates are diphenylmethane-4,4'-diisocyanate (MDI) and dicyclohexylmethane-4,4'-diisocyanate (SMDI). Furthermore, there are only a few reports describing the toxicity of these diiso...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90182-6
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abstract::Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90133-5
更新日期:1987-09-30 00:00:00
abstract::Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recen...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.02.027
更新日期:2008-08-01 00:00:00
abstract::2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidn...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8191
更新日期:1997-08-01 00:00:00
abstract::Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinos...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.07.025
更新日期:2010-10-15 00:00:00
abstract::Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2018.08.004
更新日期:2018-10-01 00:00:00
abstract::Inhaled mineral dusts and fibres can cause chronic pulmonary inflammation, often leading to permanent scarring with loss of function, but the mechanisms involved remain obscure. There are currently no good methods for monitoring inflammatory processes in situ. Positron emission tomography (PET) of suitable intravenous...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2005.02.027
更新日期:2005-09-01 00:00:00
abstract::Since it was recently shown that the addition of nicotinamide (NAM) to pulmonary alveolar macrophages (PAM) cell monolayers significantly altered their ATP pools (Nadeau and Lane, 1988), the effects of the vitamin on the metabolism of the cells, exposed or not to very short chrysotile asbestos fibers (VSF), were evalu...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90142-7
更新日期:1989-03-15 00:00:00
abstract::Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2h of re...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.11.019
更新日期:2016-01-01 00:00:00
abstract::Hexachlorobenzene (HCB)-induced porphyria occurs in female, but not male, rats after a delay of 35 days following HCB treatment. Uroporphyrinogen decarboxylase (UROD) inhibition has been proposed as a primary causative event. To determine whether there also exists a delay phase and a sexual dimorphism for UROD inhibit...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8157
更新日期:1997-07-01 00:00:00
abstract::The inter-relationship of "Thresholds" between chemical mixtures and their respective component single chemicals was studied using three sets of data and two types of analyses. Two in vitro data sets involve cytotoxicity in human keratinocytes from treatment of metals and a metal mixture [Bae, D.S., Gennings, C., Cart...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2006.11.016
更新日期:2007-09-01 00:00:00
abstract::The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposom...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.09.011
更新日期:2012-11-15 00:00:00
abstract::Previous studies from this laboratory have demonstrated that the addition of methyl groups at the 3 and 4 positions of the 2,5-hexanedione (2,5-HD) molecule results both in more rapid pyrrole formation and in enhanced neurotoxicity. In order to define more clearly the relationship between rates of pyrrole formation an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90296-1
更新日期:1987-02-01 00:00:00
abstract::This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cel...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.08.003
更新日期:2014-10-15 00:00:00
abstract::The UDP glucuronosyltransferases (UGT) of the gastrointestinal (GI) tract have a crucial role in protection against the toxic effects of lipophilic chemicals in the environment. UGTs such as UGT1A7, UGT1A8, and UGT1A10 are exclusively expressed in gastrointestinal tissues, each with a unique tissue distribution patter...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2004.01.008
更新日期:2004-09-15 00:00:00
abstract::Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Tre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.11.016
更新日期:2008-05-01 00:00:00
abstract::Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established wi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.002
更新日期:2012-12-01 00:00:00
abstract::The use of toxicokinetic (TK) data is becoming more prevalent in the evaluation of food ingredient safety as more TK information is being incorporated in safety data packages. Data demonstrating "1) the extent of absorption, 2) tissue distribution, 3) pathways and rates of metabolism, and 4) rate(s) of elimination" of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2019.114759
更新日期:2019-11-01 00:00:00
abstract::Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were ex...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2002.9390
更新日期:2002-05-01 00:00:00
abstract::CD-1 mice were treated ip on Day 10 of gestation with 4, 6, or 7 g/kg ethanol. Maternal and embryonic tissues were analyzed for ethanol and acetaldehyde levels by head-space gas chromatography 5 min to 24 hr after treatment. Dose-dependent ethanol concentrations were observed in maternal blood and liver. Ethanol rapid...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90321-1
更新日期:1984-02-01 00:00:00
abstract::Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, whi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.07.001
更新日期:2007-11-15 00:00:00
abstract::Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation seque...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115030
更新日期:2020-07-15 00:00:00
abstract::Bobwhite quail were exposed to 2,4-dinitrophenol (DNP) in a respirometer designed to continuously monitor exchange of O2 and CO2, from which metabolic rates (MR) were estimated. After 14-16 days of acclimation to the system (temperature 22 degrees C, light cycle 8L:14D), hens received feed amended with 0, 625, or 1250...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1241
更新日期:1993-12-01 00:00:00
abstract::Two hours after a four-hour exposure to hexamethylene diisocyanate trimer (HDIt) aerosol between 2.5 and 39 mg/m3, mice were injected iv with 51Cr-EDTA (chromium ethylenediaminetetraacetate). Ten minutes later the lung was lavaged. A larger amount of 51Cr-EDTA was detected in the lung lavage of HDIt mice than of contr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90269-7
更新日期:1983-07-01 00:00:00
abstract::The effect of lead exposure on beta2-adrenoceptor density and catecholamine response was studied in 26 male workers and 1 female worker, exposed to lead on average for 6 years. The systolic blood pressure in lead workers (101-160 mmHg, 124.4 +/- 14.7 mmHg) was found to be significantly higher than in controls (97-134 ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0136
更新日期:1996-07-01 00:00:00
abstract::Thiocyanate anions (SCN-) as the end products of tobacco smoke and found in the blood of cigarette smokers have been implicated in atherogenesis and heart diseases. Magnesium deficiency has also been implicated in the etiology of atherogenesis. The contractile responses of rat aorta to SCN- and the modulation of extra...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8666
更新日期:1999-05-15 00:00:00
abstract::Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of the cholinesterase inhibitor paraoxon (PO), p-nitrophenol (PNP), p-nitrophenyl sulfate (PNPS), and p-nitrophenyl glucuronide (PNPG). Daily pretreatment of mice with phenobarbital (80 mg/kg, ip) for 4 da...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90403-5
更新日期:1986-10-01 00:00:00
abstract::Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that stimulates transcription directed by xenobiotic response elements upstream of target genes. Recently, AhR ligands were reported to induce formation of an AhR-estrogen receptor (ER) complex, which can bind to estrogen response elements (ERE...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.09.011
更新日期:2006-06-01 00:00:00
abstract::In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples w...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8585
更新日期:1999-03-01 00:00:00
abstract::Exposure to the potent tumor promoter 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or related agonists of the aryl hydrocarbon receptor (AhR) can result in hepatocarcinogenesis in rodents. Changes in the expression and/or the level of growth factors may be a critical event in TCDD-mediated hepatocarcinogenesis. In this...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8460
更新日期:1998-09-01 00:00:00