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Computational binding motif analysis revealed an over-representation of dioxin response element (DREs) in the isolated regions. For example, 49% and 61% of the AHR bound regions contained at least one DRE at 2 and 24 h, respectively. Moreover, 70% of the regions in common between 2 and 24 h contained at least one DRE. Comparison of ChIP-chip data to hepatic gene expression profiles obtained from 3 week old ovariectomized, immature C57BL/6 mice orally gavaged with 30 μg/kg TCDD for 2, 4, 8, 12, 18, 24, 72, 168 h using Agilent 4 x 44K whole genome microarrays. Of the 1787 unique differentially expressed genes (|fold change| > 1.5, p1(t) > 0.95) identified across all times points, 202 regions exhibited corresponding AhR enrichment within the 2 and 24 h ChIP-chip data sets. Although there were differences in models (age), hormone status and routes of administration between ChIP-chip and microarray studies, a strong correlation was observed between known TCDD responsive genes, computationally identified putative DREs, and evidence of AhR enrichment in their regulatory regions. Funded by CIHR MOP-82715 and SBRP P42ES04911. 1199 THE AHR REGULATES CELL CYCLE PROGRESSION IN HUMAN BREAST CANCER CELLS VIA A FUNCTIONAL INTERACTION WITH CDK4. M. A. Barhoover 1 , J. M. Hall 1, 2 , W. F. Greenlee 1 and R. S. Thomas 1 . 1 The Hamner Institutes for Health Sciences, Research Triangle Park, NC and 2 Campbell University, Buies Creek, NC. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with constitutive activities as well as those induced by xenobiotic ligands, such as the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One unexplained cellular role for the AHR has been its ability to promote cell cycle progression in the absence of exogenous ligands, whereas treatment with exogenous ligands induces cell cycle arrest. Within the cell cycle, progression from G1 to S phase is controlled by sequential phosphorylation of the retinoblastoma protein (RB1) by cyclin D-CDK4/6 complexes. In this study, the functional interactions between the AHR, CDK4, and CCND1 were investigated as a potential mechanism for the cell cycle regulation by the AHR in human breast cancer cells. The results demonstrated that the AHR and CDK4 interact within the cell cycle and the interaction was disrupted upon TCDD treatment. The disruption was temporally correlated with G1 cell cycle arrest and decreased phosphorylation of RB1. Biochemical reconstitution assays using in vitro translated protein recapitulated the AHR and CDK4 interaction and showed that CCND1 was also part of the complex. In vitro assays for CDK4 kinase activity demonstrated that RB1 phosphorylation by the AHR:CDK4:CCND1 complex was reduced in the presence of TCDD. The results suggest that the AHR acts as a scaffolding protein and aids in the recruitment of RB1 to the AHR:CDK4:CCND1 complex. The recruitment of RB1 enables phosphorylation by CDK4 and facilitates cell cycle progression. Upon binding to an exogenous ligand, the AHR dissociates from CDK4 and CCND1 and the phosphorylation of RB1 is inhibited. This switch-like activity extends the current model of AHR function within the cell cycle by providing a mechanism whereby the receptor can also facilitate cell cycle progression and may help explain both the reduced mammary development in AHR knockout mice and the inhibition of mammary tumorigenesis in the rodent bioassay. 1200 ANALYSIS OF AHR PROTEIN TURNOVER IN AN ESTABLISHED YEAST EXPRESSION MODEL. S. E. Wilson, K. H. Schmidt and R. S. Pollenz. Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL. Previous studies have demonstrated that the aryl hydrocarbon receptor (AHR) is degraded following ligand binding. To generate a model system useful to screen for proteins involved in ligand-mediated AHR degradation, the cDNAs for mouse AHR and ARNT were stably integrated in the yeast genome. Initial studies have shown the AHR protein is rapidly degraded in a ligand-independent manner in these recombinant strains. The following project was designed in order to evaluate the mechanism behind this degradation event. The Erg6 cell wall protein was disrupted in the recombinant strain to allow the cells to be permeable to various protease inhibitors. Recombinant yeast was grown in the presence of galactose in order to induce expression of AHR and ARNT. Following induction, cells were incubated in the presence of MG132 or Me2SO. Protein was extracted and western blotting showed that treatment with MG132 blocked the degradation of the AHR. This implicates the 26S proteasome in the ligand-independent degradation of the AHR is this yeast model. In addition, no reduction in AHR degradation could be observed when the yeast were treated with calpain inhibitors. Since MG132 also cause an induction in expression of heat shock proteins (HSP) and these proteins are essential for the proper folding and stability of the AHR, studies next evaluated whether the MG132 prevented AHR degradation as a result of increased HSP90 expression. To address this question, a constitutive Hsp90 expression plasmid was transformed into yeast and the stability of the AHR directly evaluated by western blotting. The overexpression of mammalian HSP90 did not significantly stabilize the AHR protein. These results suggest i) that the ligand-independent degradation of the AHR in the recombinant yeast system is mediated by the 26S proteasome and ii) that the degradation is not the result of limiting levels of HSP90 expression. This model may be useful for future studies aimed at determining the mechanism of AHR degradation and the sites that are modified by ubiquitin. (ES015481) 1201 DEVELOPING A MONOCLONAL ANTIBODY BASED CAPTURE ASSAY TO QUANTIFY CYTOSOLIC AHR. A. S. Devasthanam 1 , N. J. Alles 1 , C. M. Vezina 2 , J. R. Olson 1 and K. Rittenhouse-Olson 1 . 1 University at Buffalo, Buffalo, NY and 2 University of Wisconsin, Madison, WI. The Aryl Hydrocarbon Receptor (AHR) is a ligand inducible cytosolic transcription factor that up- and down-regulates genes, resulting in a wide range of biological and toxicological responses. Although several studies have assessed AHR mRNA levels following exposure to polycyclic aromatic hydrocarbons and other AHR ligands, an antibody-based assay to quantify cytosolic AHR has yet to be established. Anti-AHR monoclonal antibodies to conserved peptide sequences at the N- and C- terminal of the AHR were used to capture AHR in hepatic cytosol fractions. The purified monoclonal antibodies have been shown to be reactive at levels as low as 5ng/ml when tested in an indirect enzyme immunoassay with the respective AHR peptide conjugates. Mouse Hepa-1 cytosol, cited to have the most abundant source of AHR, was used as one source of AHR. Cytosol preparations were also obtained from liver tissue samples of mice (C57BL/6 and BALB/c), AHR -/- mice, rat (Sprague Dawley) and human. Western blotting confirmed good species cross-reactivity of the monoclonal antibodies, with no signal present in cytosol from AHR -/- mice. The capture assay utilized either monoclonal anti-AHR developed to the N- terminal peptide, or monoclonal anti-AHR developed to the C-terminal peptide as the capture antibody. Next, application of cytosol preparations were followed by a detection system which consists of a goat anti-AHR and an alkaline phosphatase conjugated anti-goat secondary antibody. The capture assay gave a consistent linear signal with liver cytosol samples from mouse, rat and human (0.3μg – 40μg total cytosol protein per well). The AHR monoclonal antibodies and capture assay for cytosol AHR will provide valuable tools for future studies on the function and regulation of the AHR. (supported by NIEHS grant RO3 ES012911) 1202 AHR-MEDIATED GENE EXPRESSION IN THE DEVELOPING MOUSE HEART. X. Chang, R. Thomas, J. Foley, F. M. Parham and C. J. Portier. NIEHS, Reseach Triangle Park, NC. 2,3,7,8-tetrachlorodibenzio-p-dioxin (TCDD) is an ubiquitous persistent environmental contaminant that exerts a broad range of toxic effects including disruption of cardiovascular development. In this study, we hypothesize that TCDD induced developmental cardiovascular toxicity is mediated through inappropriate AHR activation which alters expression of key genes/pathways during mouse cardiac development. To test this hypothesis we examined global gene expression in heart tissues of the E13.5 Ahr -/- and wild type C57BL/6 mouse embryos exposed in utero to TCDD or vehicle. In agreement with previous reports, our results showed few statistically significant gene expression changes after TCDD exposure in Ahr -/- mice, suggesting that TCDD initiated changes in gene expression in the developing heart are primarily AHR dependent. The total numbers of genes of significant change in expression after knocking-out AHR are five times higher than those after TCDD exposure in wt mice, indicating that AHR ablation has more profound effects on heart development than acute TCDD exposure. In addition, half of the genes with significantly increased expression after TCDD exposure in wt mice are also found to be significantly increased after AHR ablation, suggesting that TCDD induced toxicity is at least partially caused by disturbance of physiological functions of AHR. Further comparative genomics analysis suggests several genes (e.g. Sox11) are novel targets directly regulated by AHR. Finally, through pathway analysis, we were able to identify several key regulatory pathways that are potentially involved in AHR mediated and/or TCDD induced cardiovascular toxicity, which includes retinol metabolism, rennin-angiotensin system, PPAR signaling pathway, complement and coagulation cascades, and C21-steroid hormone metabolism. In conclusion, this analysis supports the hypothesis that AHR has a specific role in the normal heart development and provides a mechanistic framework for cardiovascular toxicity of chemicals that perturb AHR signaling. 256 SOT 2010 ANNUAL MEETING
1203 ARYL HYDROCARBON RECEPTOR-DNA BINDING AND FUNCTION INVOLVING A NOVEL REGULATORY ELEMENT INDEPENDENT OF THE ARNT PROTEIN. G. Huang and C. Elferink. Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of modulating gene expression by binding to a well characterized xenobiotic response element (XRE), in response to agonists such as tetrachlorodibenzo-pdioxin (TCDD). However, DNA microarray experiments performed in several laboratories including ours, identified numerous AhR target genes lacking an obvious XRE in the promoter or flanking regulatory regions. Our examination of one such gene, encoding plasminogen activator inhibitor type 1, identified and characterized a new non-consensus XRE (NC-XRE) that binds the AhR independently of the canonical Arnt protein dimerization partner. Luciferase reporter expression studies and electrophoretic mobility shift assays confirmed AhR involvement and defined key nucleotides within the NC-XRE necessary for binding and function. Chromatin immunoprecipitation and shRNA-mediated Arnt protein knock-down studies demonstrated that AhR-mediated activity through the NC-XRE does not require the Arnt protein. Collectively, the evidence suggests that the NC-XRE represents a novel AhR binding site that defines a subset of target genes responsive to TCDD, distinct from the classical AhR/Arnt-regulated genes. Supported by the NIEHS grants ES007800 and ES012018. 1204 TCDD INDUCED PERICARDIAL EDEMA AND RELATIVE COX-2 EXPRESSION IN MEDAKA EMBRYOS. W. Dong 1, 2 , F. Matsumura 3 and S. W. Kullman 1 . 1 Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC, 2 College of Marine Science, HuaiHai Institute of Technology, LianyunGang, Jiangsu, China and 3 Environmental Toxicology, University of California Davis, Davis, CA. Dioxin and other AhR ligands are well known to result in multiple defined developmental phenotypes including pericardial edema and circulation failure in small aquarium fish models. While these phenotypes are well describe, the mechanistic underpinning behind these toxicities manly remain elusive. To date, much of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) toxicity is thought to be due to the classical genomic actions of AhR/ARNT transcription factor complex. Here we suggest that AhR additionally functions through a non-classical, non-genomic mechanism(s) involving activation of inflammation and eicosanoid pathways. We demonstrate that medaka embryos exposed to TCDD (0.5-1 ppb) during early development result in a dose related increase in the prevalence of pericardial edema and that this phenotype correlates with modification of both Cyclooxygenase-2 (Cox-2) activity and gene expression in exposed medaka embryos. TCDD exposure significantly induces Cox-2 and CYP1A1 mRNA in all treated embryos. Those individuals exhibiting the edema phenotype were found to have significantly greater abundance of Cox-2 mRNA than the non-edema cohort. Biochemical inhibition of Cox-2 with NS-398 a selective Cox-2 inhibitor, significantly attenuates the prevalence and severity of edema phenotype. Subsequently, exposures of medaka embryos to Arachidonic Acid (AA) resulted in recapitulation of the pericardial edema phenotype and significantly increased Cox-2 expression only in those individuals exhibiting pericardial edema compared to the non-edema cohort. Interestingly, AA exposure does not result in any significant induction of CYP1A expression. Taken together, these results indicate a putative correlation between TCDD induced pericardial edema and relative cox-2 mediated prostaglandin pathway in the medaka embryos. This work was supported by NCARS (02225), NCET-04-0262 and NSFC (30360090) 1205 A RAPID, CELL-BASED BIOLUMINESCENT ARYL HYDROCARBON RECEPTOR ACTIVATION ASSAY THAT USES CYP1A1 ENZYME ACTIVITY AS A SELECTIVE MARKER ACTIVITY. J. Cali, D. Ma and P. Meisenheimer. Research and Development, Promega Corporation, Madison, WI. Sponsor: A. Li. The aryl hydrocarbon nuclear receptor is activated for positive transcriptional regulation by small molecule drugs and toxins. An example of an AHR responsive gene is cytochrome P450 1A1 and this gene can be used as a marker for AHR activity. CYP1A1 expression can be measured at the levels of mRNA, protein expression and enzyme activity. Here we describe a rapid, non-destructive bioluminescent cell based assay for monitoring CYP1A1 enzyme activity as a marker of AHR activity. The assay uses a cell permeable bioluminogenic CYP1A1 substrate. Bioluminogenic substrates are proluciferins that are converted by the enzymes of interest to a luciferin that is detected in a bioluminescent reaction with luciferase, correlating light output with target enzyme activity. The bioluminogenic CYP1A1 substrate is a novel luciferin derivative that showed exquisite CYP1A1 selectivity over all other CYPs from a panel of 21 that were tested, including CYP1A2 and CYP1B1. The assay detected robust activations by known AHR agonists in a 96 well format that left cells intact for further analysis. While induction data with this assay correlated well with conventional mRNA and protein analysis methods, the luminescent assays were simpler, more rapid and by leaving cells intact allowed for a multiplexed assay that measured cell viability and AHR activity from single culture well. This bioluminescent assay enables a high throughput cell-based method for screening of AHR agonists. 1206 SYNERGY BETWEEN ARYL HYDROCARBON RECEPTOR AND CONSTITUTIVE ANDROSTANE RECEPTOR ACTIVATION PROMOTES MURINE LIVER HYPERPLASIA. S. Wilson 1 , K. Mitchell 2 and C. Elferink 1 . 1 Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX and 2 Biological Sciences, Boise State University, New London, CT. Mechanisms of hepatocyte proliferation triggered by tissue loss are distinguishable from those that promote proliferation in the intact liver in response to mitogens. Previous studies demonstrate that exogenous activation of the aryl hydrocarbon receptor (AhR), a soluble ligand-activated transcription factor in the basic helix-loophelix family of proteins, suppresses compensatory liver regeneration elicited by surgical partial hepatectomy (PH). The goal of the present study was to determine how AhR activation modulates hepatocyte cell cycle progression in the intact liver following treatment with the hepatomitogen, 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP). Mice were pretreated with the exogenous AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 24 hours prior to treatment with TCPOBOP (3 mg/kg), a potent agonist for the constitutive androstane receptor (CAR), which is known to induce hepatocyte proliferation. In contrast to the suppressive effects of AhR activation observed during compensatory regeneration, TCDD pretreatment resulted in a 30-50% increase in hepatocyte proliferation in the intact liver of TCPOBOP-treated mice. Pretreatment with TCDD suppressed CDK2 kinase activity and increased the association of CDK2 with negative regulatory proteins p21Cip1 and p27Kip1, yet increased CDK4/cyclin D1 association and CDK4 activity, which culminated in enhanced phosphorylation of retinoblastoma protein. Moreover, pretreatment with TCDD transiently increased levels of CAR transcript and activity, which coincided with elevated levels of CAR protein and cyclin D1 expression. Based on these findings, we conclude that AhR activation potentiates TCPOBOP-stimulated hepatocyte proliferation through a mechanism that may include increased CDK4 kinase activity as well as elevated CAR expression and activity. Supported by the NIEHS Grant ES007800 (C. E.), F32ES013588 (K. M.), and F30ES016490 (S. W.). 1207 TELOMERASE INHIBITION BY ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS IN HUMAN MAMMARY EPITHELIAL CANCER CELLS. S. Pittet and M. Charbonneau. INRS-Institut-Armand-Frappier, Université du Québec, Laval, QC, Canada. Persistent organic pollutants (POP) are ubiquitous lipophilic chemicals. POP exposure has been suggested as a risk factor for breast cancer development based on some epidemiological and rodents studies. Other data suggest, however, that AhR agonists can cause anticarcinogenic effects. Telomerase expression is a key pro-carcinogenic component responsible for increased cancer cell longevity. This work aimed to test the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other AhR agonists on cell proliferation and telomerase expression in human epithelial mammary cancer cells. TCDD (5.3 nM, 6 d) decreased cell proliferation in two AhR-positive mammary cell lines, the estrogen receptor (ER)-positive T47D (36 % lower) and the ER-negative MDA-MB-231 (26 % lower). Telomerase activity, measured with the TRAPeze® XL Telomerase Detection Kit, was significantly reduced in both cell lines, T47D (34 % lower) and MDA-MB-231 (26 % lower). Similar results were observed with mixtures of PCBs, PCDFs and PCDDs. TCDD exposure of the AhR-negative neuronal cell line, SH-SY5Y (ER-), did not affect cell proliferation rate nor telomerase activity. These data suggest an AhR-dependent pathway. Western Blot analyses showed a significant 2-fold decrease in the cytoplasmic AhR level in TCDD-treated (5.3 nM, 24 h) T47D cells compared to controls (DMSO), suggesting AhR activation and its nuclear translocation. Real-Time PCR quantification of the mRNA levels for the catalytic subunit of telomerase, hTERT, showed a down-regulation in gene expression consistent with the presence of inhibitory Dioxin Response Elements (iDRE) in the hTERT gene sequence. Overall, these results demonstrate that AhR agonists cause a receptor-dependent down-regulation of telomerase transcription and subsequent reduction in cell proliferation, suggesting anticarcinogenic effects in human mammary cancer cells. Inhibition of telomerase expression by AhR agonists may represent a therapeutic pathway for breast cancer treatment SOT 2010 ANNUAL MEETING 257
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
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portant in predicting risk. CYPs 1A
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ats, which involves metabolic activ
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473 BOVINE CORNEAL OPACITY AND PERM
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482 TYPE III DEIODINASE (D3) IS PRO
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tancy evaluation and ranking of bat
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501 CHARACTERIZATION OF ESTERASE, G
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510 REDOX CYCLING BY ENDOGENOUS 2-
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prostate cancer cells. All 8 BEL de
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metallic nickel nanoparticles. Acti
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variety of more or less reactive ch
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550 QUALIFICATION STRATEGIES-GENOTO
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ferentiation, and 3) how mixtures o
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572 LOW-CHRONIC ARSENIC EXPOSURE: E
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582 IDENTIFICATION OF SENSITIVE URI
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duced by the genetic outcross of fe
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fects of new compounds are equally
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acterize the current state of the s
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620 CHARACTERIZATION OF POTENTIAL I
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ways. Moreover, both MAP kinase and
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641 POPS IN THE U.S. POPULATION AND
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studies such as the NCS, consider h
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the beginning of the academic caree
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trophil infiltration, a significant
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tactic response and optokinetic res
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usually high spontaneous PIG-A MFs.
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699 PROMUTAGEN ACTIVATION AND P450
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oxodG in bone marrow, spleen, kidne
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718 GENOTOXICITY OF ORGANIC EXTRACT
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ment were 18.0 and 4.5 nM for BEAS-
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strongest activation of nuclear fac
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746 MACROPHAGE INHIBITORY CYTOKINE-
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screening of cell migration. High-c
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dase inhibition). In contrast, inhi
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mice; the decrease was more pronoun
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Markers of oxidative damage reached
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793 PULMONARY RESPONSE, OXIDATIVE S
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cilitate clinical and industrial ap
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sion of p-p38, p-p53, p21 and cycli
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821 KIDNEY INJURY MOLECULE-2 GENE D
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commercial applications, and have b
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developmental effects. The residual
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strand breaks in an in vitro model
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etate (immunotoxicity). 2,4-D was t
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867 MELATONIN AMELIORATES CYCLOPHOS
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pharmacokinetic (PBPK) models. Ten
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of radiolabeled Mn (carrier-free 54
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893 UNVEILING ASSOCIATIONS BETWEEN
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using area under the concentration
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912 COMMERCIAL FISH DIETS INDUCE VI
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922 A STUDY OF PHOTOTOXICITY FOLLOW
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from 0.1 to 2.9 g/L (saturated vapo
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vasive method for assessing several
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950 ARSENITE DOWN-REGULATES THE CAR
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Page 245 and 246: zebrafish cells were first exposed
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1448 ADVERSE OUTCOME PATHWAYS AND E
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the level in urine was 25% of the m
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1;akt-2 double mutant and pdk-1 mut
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jury effects when compared to contr
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tude than equivalent oral doses. Af
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cells; and increased iNOS and MCP-1
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B6.Cg-Kit W-sh mice. These findings
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1511 STATIN-TREATMENT EFFECTIVELY R
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1520 EFFECT OF INHALATION EXPOSURE
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numbers of IFN-γ producing cells w
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These data indicate that TCDD treat
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esponse to allogenic cells, where P
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larly suppressed LPS-induced TNF-α
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1565 INFLUENCE OF EXPOSURE ROUTE AN
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veloping animals to adverse effects
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the observed CL values were 0.07 L/
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which is most relevant for potentia
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tive impairment, suggesting that ox
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1611 AN IN VITRO METABOLOMICS APPRO
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Expression of the β6 integrin (Itg
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ats (10 μg/kg TCDD). Here we repor
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at liver slices and how the metabon
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with gender differences in AUC and
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oxetine (30 mg/kg reduced to 15 mg/
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eleased from necrotic cells where i
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plants, they are present in surface
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ferentiation (quantitative in-cell
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control for macrophage activation).
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to 0.5μg/ml. Minimal inhibitory co
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lines tested. Given that dex and AT
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tion in the absence of an immune re
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treated rats had lower calcium load
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1740 PROFILING COMPOUNDS WITH CARDI
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dothelial cells confirmed caveolin-
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1758 GINKGO BILOBA EXTRACT INDUCES
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arin-induced suppression of MDR1 ex
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1780 ANTIANDROGENIC AND ANTIPROLIFE
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included in the evaluation, most of
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1799 GUIDANCE ON THE APPLICATION OF
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However, substances with EC3 values
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1816 CD-INDUCED EGFR TRANSACTIVATIO
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1826 KERATIN 7 EXPRESSION IN INDEPE
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centa were collected at the time of
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1845 SYSTEMATIC SCREENING OF YEAST
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underlying the development of co-mo
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eing measured in experimental roden
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ufactured in the US for more than 3
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nine (N7-THB-Gua) and N7-hydroxyphe
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1892 EFFECT OF LAMBDA-CYHALOTHRIN O
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22 in Phase I. Antimicrobial pestic
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kinetic and dynamic differences, an
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iphenyl, saccharin and melamine was
Page 415 and 416:
1930 DEVELOPMENT OF A RELATIVE SOUR
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1939 MODE OF ACTION FOR THE CANCER
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human was about 1.5-fold lower (60
Page 421 and 422:
Disruption of BDEC integrity in alp
Page 423 and 424:
1968 A HUMAN HEPG2 LUCIFERASE ASSAY
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in the offspring during tumor devel
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een developed to investigate perfus
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to 131.73 μg/mL for KLH-specific I
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cell lines (ATCC) were cultured in
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flammation and xenobiotic metabolis
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vide many contributions: with its g
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to-metal joint replacement. For exa
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to be addressed or negotiated. Deci
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especially with anti-TNF therapies.
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genic line Tg(are:eGFP) was created
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2074 COMPUTATIONAL ASSESSMENT OF TH
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2084 INHIBITION OF 11β-HSD1 DECREA
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(T) and express several enzymes inv
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2101 GENISTEIN MODULATION OF BLOOD
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males per group were dosed orally o
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ate the feasibility of assessing re
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changed. Hepatic protein carbonyl l
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sought to examine alterations in he
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2147 A SINGLE AMINO ACID CONTROLS T
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Gstm7) was independent of both CAR
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ility of tungsten trioxide (WO3), t
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ured by real-time PCR array and rel
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glucose, and creatinine levels, and
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Several studies have reported suppr
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exposure between TCDD-exposed labor
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Furthermore, with increasing number
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Society of Toxicology 2010 Author I
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Society of Toxicology 2010 Abstract
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49 th Annual Meeting and ToxExpo A
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The Official Journal of the Society
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