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Locale: United States

Top Publications

  1. Kransler K, McGarrigle B, Russell R, Olson J. Effects of Helicobacter infection on developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Holtzman rats. Lab Anim (NY). 2008;37:171-5 pubmed publisher
    ..All rats were affected by TCDD, and Helicobacter infection seemed to have little influence on rats' susceptibility to the compound. ..
  2. Branam A, Davis N, Moore R, Schneider A, Vezina C, Peterson R. TCDD inhibition of canonical Wnt signaling disrupts prostatic bud formation in mouse urogenital sinus. Toxicol Sci. 2013;133:42-53 pubmed publisher
    ..We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation. ..
  3. Lew B, Collins L, O Reilly M, Lawrence B. Activation of the aryl hydrocarbon receptor during different critical windows in pregnancy alters mammary epithelial cell proliferation and differentiation. Toxicol Sci. 2009;111:151-62 pubmed publisher
    ..These varying outcomes in mammary development due to exposure at different times in pregnancy suggest there are critical windows during which AhR activation impairs mammary epithelial cell proliferation and differentiation. ..
  4. Liu Z, Wall J, Barge P, Dettmann M, Ottinger N. Investigation of PCDD/F emissions from mobile source diesel engines: impact of copper zeolite SCR catalysts and exhaust aftertreatment configurations. Environ Sci Technol. 2011;45:2965-72 pubmed publisher
    ..Furthermore, experiments performed with high chlorine concentration provided no evidence that chlorine content has an impact on the catalytic synthesis of PCDD/Fs for the chlorine levels investigated in this study. ..
  5. Ray S, Swanson H. Dioxin-induced immortalization of normal human keratinocytes and silencing of p53 and p16INK4a. J Biol Chem. 2004;279:27187-93 pubmed
    ..More importantly, this is the first report of a tumor promoter capable of inhibiting senescence in a receptor mediated manner and introduces a novel mechanism by which this carcinogen may contribute to human malignancies. ..
  6. Williamson M, Gasiewicz T, Opanashuk L. Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity. Toxicol Sci. 2005;83:340-8 pubmed
    ..These data suggest that (1) granule neuroblasts are direct targets for developmental AhR-mediated TCDD neurotoxicity and (2) TCDD exposure may disrupt granule cell neurogenesis. ..
  7. Mandal P, McDaniel L, Prough R, Clark B. 7,12-Dimethylbenz[a]anthracene inhibition of steroid production in MA-10 mouse Leydig tumor cells is not directly linked to induction of CYP1B1. Toxicol Appl Pharmacol. 2001;175:200-8 pubmed
    ..CYP1B1 expression levels, however, cannot be directly correlated to potential in vitro or in vivo toxic effects of TCDD or DMBA. ..
  8. Chen Y, Dong H, Thompson D, Shertzer H, Nebert D, Vasiliou V. Glutathione defense mechanism in liver injury: insights from animal models. Food Chem Toxicol. 2013;60:38-44 pubmed publisher
    ..Collectively, these transgenic mouse models provide interesting new insights regarding pathophysiological functions of GSH in the liver. ..
  9. Beischlag T, Perdew G. ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription. J Biol Chem. 2005;280:21607-11 pubmed
    ..Taken together these data support a role for ER-mediated transrepression of AHR-dependent gene regulation. ..

More Information


  1. Laiosa M, Lai Z, Thurmond T, Fiore N, DeRossi C, Holdener B, et al. 2,3,7,8-tetrachlorodibenzo-p-dioxin causes alterations in lymphocyte development and thymic atrophy in hemopoietic chimeras generated from mice deficient in ARNT2. Toxicol Sci. 2002;69:117-24 pubmed
    ..These data indicate that in this model system the effects of TCDD-induced thymic atrophy and alterations in B-cell maturation are not dependent on an AHR-ARNT2 heterodimer. ..
  2. Lin T, Rasmussen N, Moore R, Albrecht R, Peterson R. Region-specific inhibition of prostatic epithelial bud formation in the urogenital sinus of C57BL/6 mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2003;76:171-81 pubmed
    ..Inhibited bud formation appears to be the primary cause of abnormal prostate development in TCDD-exposed mice. ..
  3. Ndebele K, Tchounwou P, McMurray R. Coumestrol, bisphenol-A, DDT, and TCDD modulation of interleukin-2 expression in activated CD+4 Jurkat T cells. Int J Environ Res Public Health. 2004;1:3-11 pubmed
  4. Ndebele K, Graham B, Tchounwou P. Estrogenic activity of coumestrol, DDT, and TCDD in human cervical cancer cells. Int J Environ Res Public Health. 2010;7:2045-56 pubmed publisher
    ..These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer. ..
  5. Henry E, Welle S, Gasiewicz T. TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts. Toxicol Sci. 2010;114:90-100 pubmed publisher
    ..Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible. ..
  6. Franceschini M, Custer C, Custer T, Reed J, Romero L. Corticosterone stress response in tree swallows nesting near polychlorinated biphenyl- and dioxin-contaminated rivers. Environ Toxicol Chem. 2008;27:2326-31 pubmed publisher
    ..Altogether these findings suggest that tree swallows chronically exposed to high PCB and TCDD levels exhibit altered baseline and stress-induced corticosterone responses, but the patterns of alteration might not be predictable...
  7. Henry E, Gasiewicz T. Agonist but not antagonist ligands induce conformational change in the mouse aryl hydrocarbon receptor as detected by partial proteolysis. Mol Pharmacol. 2003;63:392-400 pubmed
    ..We conclude that agonist ligands initiate structural alteration in AhR that is Arnt-dependent and at least partially involves the ligand-binding/Per-Arnt-Sim domain. ..
  8. Petroff B, Roby K, Gao X, Son D, Williams S, Johnson D, et al. A review of mechanisms controlling ovulation with implications for the anovulatory effects of polychlorinated dibenzo-p-dioxins in rodents. Toxicology. 2001;158:91-107 pubmed
    ..PCDDs interrupt ovulation through direct effects on the ovary in combination with dysfunction of the hypothalamo-hypophyseal axis. ..
  9. Jin G, Moore A, Head J, Neumiller J, Lawrence B. Aryl hydrocarbon receptor activation reduces dendritic cell function during influenza virus infection. Toxicol Sci. 2010;116:514-22 pubmed publisher
    ..Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection. ..
  10. Ovando B, Ellison C, Vezina C, Olson J. Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands. BMC Genomics. 2010;11:583 pubmed publisher
    ..In addition, the time independent gene expression signature of the AhR ligands may assist in identifying other agents with the potential to elicit dioxin-like hepatotoxic responses. ..
  11. Funatake C, Marshall N, Kerkvliet N. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters the differentiation of alloreactive CD8+ T cells toward a regulatory T cell phenotype by a mechanism that is dependent on aryl hydrocarbon receptor in CD4+ T cells. J Immunotoxicol. 2008;5:81-91 pubmed publisher
  12. Prasch A, Teraoka H, Carney S, Dong W, Hiraga T, Stegeman J, et al. Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish. Toxicol Sci. 2003;76:138-50 pubmed
    ..Most strikingly, zfahr2 morphants exposed to TCDD never developed edema. Taken together, these results demonstrate that zfAHR2 mediates several endpoints of TCDD developmental toxicity in zebrafish. ..
  13. Lu H, Cui W, Klaassen C. Nrf2 protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis. Toxicol Appl Pharmacol. 2011;256:122-35 pubmed publisher
    ..The aggravated hepatosteatosis in TCDD-treated Nrf2-null mice is due to increased lipogenesis in liver and impaired lipogenesis in white adipose tissue. ..
  14. McMillan B, McMillan S, Glover E, Bradfield C. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces premature activation of the KLF2 regulon during thymocyte development. J Biol Chem. 2007;282:12590-7 pubmed
    ..These findings indicate that the pollutant TCDD interferes with early thymopoeisis via ectopic expression of the KLF2 regulon. ..
  15. Kransler K, McGarrigle B, Swartz D, Olson J. Lung development in the Holtzman rat is adversely affected by gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2009;107:498-511 pubmed publisher
  16. Fried K, Schneider C, Schramm K, Datta A, Chahbane N, Corsten C, et al. From dioxin to drug lead--the development of 2,3,7,8-tetrachlorophenothiazine. ChemMedChem. 2007;2:890-7 pubmed
    ..4 h in the rat and 2.7 h in the guinea pig, compared to 11 and 30 days, respectively, for TCDD. These initial findings clearly differentiate TCPT from TCDD and provide the basis for further studies of its potential as a drug lead. ..
  17. Rohlman D, Punj S, Pennington J, Bradford S, Kerkvliet N. Suppression of acute graft-versus-host response by TCDD is independent of the CTLA-4-IFN-?-IDO pathway. Toxicol Sci. 2013;135:81-90 pubmed publisher
    ..Together, these results indicate that neither overexpression of CTLA-4 nor production of IFN-? by AhR-Tregs plays a major role in the manifestation of their immunosuppressive function in vivo. ..
  18. Budinsky R, LeCluyse E, Ferguson S, Rowlands J, Simon T. Human and rat primary hepatocyte CYP1A1 and 1A2 induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran. Toxicol Sci. 2010;118:224-35 pubmed publisher
    ..Overall, these data support the position that humans are less sensitive than rats to these AHR-dependent end points and support the use of a data-derived adjustment factor of 1.0 or less for extrapolating between rats and humans. ..
  19. Rowlands J, Budinsky R, Gollapudi B, Novak R, Abdelmegeed M, Cukovic D, et al. Transcriptional profiles induced by the Aryl Hydrocarbon Receptor agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran in primary rat hepatocytes. Chemosphere. 2011;85:232-8 pubmed publisher
  20. Kerkvliet N. TCDD: an environmental immunotoxicant reveals a novel pathway of immunoregulation--a 30-year odyssey. Toxicol Pathol. 2012;40:138-42 pubmed publisher
    ..The ability to induce Tregs using an exogenous AHR ligand to activate the AHR-Treg pathway represents a novel approach to the prevention and/or treatment of autoimmune disease. We are currently searching for such ligands. ..
  21. Cherrington N, Hartley D, Li N, Johnson D, Klaassen C. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther. 2002;300:97-104 pubmed
    ..We conclude that rat hepatic Mrp3 is induced by CAR activators, thus enhancing the vectoral excretion of some phase II metabolites from the liver to the blood. ..
  22. Lin T, Ko K, Moore R, Buchanan D, Cooke P, Peterson R. Role of the aryl hydrocarbon receptor in the development of control and 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed male mice. J Toxicol Environ Health A. 2001;64:327-42 pubmed
  23. Willett K, Wassenberg D, Lienesch L, Reichert W, Di Giulio R. In vivo and in vitro inhibition of CYP1A-dependent activity in Fundulus heteroclitus by the polynuclear aromatic hydrocarbon fluoranthene. Toxicol Appl Pharmacol. 2001;177:264-71 pubmed
    ..Because FL and perhaps other inhibitory PAHs, co-occur in the environment with CYP1A inducers, CYP1A-dependent bioassays may cause an underestimation of PAH exposures. ..
  24. Chuang J, Van Emon J, Schrock M. High-throughput screening of dioxins in sediment and soil using selective pressurized liquid extraction with immunochemical detection. Chemosphere. 2009;77:1217-23 pubmed publisher
    ..6-29% based on the relative percentage difference (%RPD) for duplicate samples. Estimated sample throughput for the SPLE-ELISA was three times or more than that of the GC/HRMS method employing PLE with a multi-column cleanup. ..
  25. Carney S, Prasch A, Heideman W, Peterson R. Understanding dioxin developmental toxicity using the zebrafish model. Birth Defects Res A Clin Mol Teratol. 2006;76:7-18 pubmed
  26. Puppala D, Lee H, Kim K, Swanson H. Development of an aryl hydrocarbon receptor antagonist using the proteolysis-targeting chimeric molecules approach: a potential tool for chemoprevention. Mol Pharmacol. 2008;73:1064-71 pubmed publisher
    ..Our results demonstrate the "proof of concept" of this approach in effectively blocking AHR activity in cultured cells. ..
  27. Volz D, Belanger S, Embry M, Padilla S, Sanderson H, Schirmer K, et al. Adverse outcome pathways during early fish development: a conceptual framework for identification of chemical screening and prioritization strategies. Toxicol Sci. 2011;123:349-58 pubmed publisher
    ..Linked with biologically based concentration-response models, a tiered testing strategy may help reduce the reliance on long-term and costly FELS tests required for assessing the hazard of thousands of chemicals currently in commerce. ..
  28. Mathew L, Sengupta S, Ladu J, Andreasen E, Tanguay R. Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish. FASEB J. 2008;22:3087-96 pubmed publisher
    ..Collectively, these results indicate that inappropriate regulation of R-Spondin/LRP6 is absolutely required for TCDD to inhibit fin regeneration. ..
  29. Shi L, Faith N, Nakayama Y, Suresh M, Steinberg H, Czuprynski C. The aryl hydrocarbon receptor is required for optimal resistance to Listeria monocytogenes infection in mice. J Immunol. 2007;179:6952-62 pubmed
    ..monocytogenes. These data provide the first evidence that AhR is required for optimal resistance but is not essential for adaptive immune response to L. monocytogenes infection. ..
  30. Vezina C, ALLGEIER S, Moore R, Lin T, Bemis J, Hardin H, et al. Dioxin causes ventral prostate agenesis by disrupting dorsoventral patterning in developing mouse prostate. Toxicol Sci. 2008;106:488-96 pubmed publisher
    ..Disrupted axial patterning provides a new paradigm for understanding how in utero TCDD exposure causes ventral prostate agenesis and may shed light on how TCDD impairs development of other organs. ..
  31. Shah S, Freedland S, Aronson W, Kane C, Presti J, Amling C, et al. Exposure to Agent Orange is a significant predictor of prostate-specific antigen (PSA)-based recurrence and a rapid PSA doubling time after radical prostatectomy. BJU Int. 2009;103:1168-72 pubmed publisher
    ..These findings suggest that among selected men who choose RP, AO exposure might be associated with more aggressive prostate cancer. ..
  32. Andreasen E, Mathew L, LOHR C, Hasson R, Tanguay R. Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling during zebra fish fin regeneration. Toxicol Sci. 2007;95:215-26 pubmed
    ..Quantitative real-time PCR studies revealed that the aryl hydrocarbon pathway is active and that matrix-remodeling genes are expressed in the regenerate following TCDD exposure. ..
  33. Ruby C, Leid M, Kerkvliet N. 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer activation is not affected. Mol Pharmacol. 2002;62:722-8 pubmed
    ..These results suggest that TCDD may alter the balance between NF-kappaB/Rel heterodimers and transcriptional inhibitory p50 homodimers in DCs, leading to defects in the DCs and suppression of the immune response. ..
  34. Lin T, Ko K, Moore R, Simanainen U, Oberley T, Peterson R. Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol Sci. 2002;68:479-87 pubmed
  35. Mathew L, Andreasen E, Tanguay R. Aryl hydrocarbon receptor activation inhibits regenerative growth. Mol Pharmacol. 2006;69:257-65 pubmed
    ..With the plethora of molecular and genetic techniques that can be applied to larval-stage embryos, this in vivo regeneration system can be further exploited to understand cross-talk between AHR and other signaling pathways. ..
  36. Roby K. Alterations in follicle development, steroidogenesis, and gonadotropin receptor binding in a model of ovulatory blockade. Endocrinology. 2001;142:2328-35 pubmed
    ..It appears that critical steps in the development and maturation of follicles are disrupted by TCDD. ..
  37. Antkiewicz D, Burns C, Carney S, Peterson R, Heideman W. Heart malformation is an early response to TCDD in embryonic zebrafish. Toxicol Sci. 2005;84:368-77 pubmed
    ..We conclude that the developing heart is an important target for TCDD in zebrafish. ..
  38. Klinge C, Jernigan S, Risinger K, Lee J, Tyulmenkov V, Falkner K, et al. Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT). Arch Biochem Biophys. 2001;390:64-70 pubmed
    ..SHP inhibited AHR/ARNT-DNA binding in vitro. These results identify ARNT as a novel SHP target. We speculate a role for SHP in the suppression of agonist-activated AHR/ARNT activity. ..
  39. Plavicki J, Hofsteen P, Peterson R, Heideman W. Dioxin inhibits zebrafish epicardium and proepicardium development. Toxicol Sci. 2013;131:558-67 pubmed publisher
    ..Epicardium development is crucial to heart development. Loss of this layer during development may account for most if not all of the TCDD-induced cardiotoxicity in zebrafish. ..
  40. Hogaboam J, Moore A, Lawrence B. The aryl hydrocarbon receptor affects distinct tissue compartments during ontogeny of the immune system. Toxicol Sci. 2008;102:160-70 pubmed
  41. Lanham K, Prasch A, Weina K, Peterson R, Heideman W. A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity. PLoS ONE. 2011;6:e28020 pubmed publisher
    ..These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity. ..
  42. Mehta V, Peterson R, Heideman W. 2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure prevents cardiac valve formation in developing zebrafish. Toxicol Sci. 2008;104:303-11 pubmed publisher
  43. Sadek C, Allen Hoffmann B. Suspension-mediated induction of Hepa 1c1c7 Cyp1a-1 expression is dependent on the Ah receptor signal transduction pathway. J Biol Chem. 1994;269:31505-9 pubmed
    ..These data directly demonstrate that suspension of wild-type Hepa 1c1c7 cells leads to nuclear localization and activation of the Ah receptor to a DNA-binding form. ..
  44. Ko K, Theobald H, Moore R, Peterson R. Evidence that inhibited prostatic epithelial bud formation in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed C57BL/6J fetal mice is not due to interruption of androgen signaling in the urogenital sinus. Toxicol Sci. 2004;79:360-9 pubmed
    ..Collectively, these results suggest that TCDD inhibits prostatic epithelial bud formation without impairing the androgen receptor signaling pathway. ..
  45. Ansbaugh N, Shannon J, Mori M, Farris P, Garzotto M. Agent Orange as a risk factor for high-grade prostate cancer. Cancer. 2013;119:2399-404 pubmed publisher
    ..These findings may aid in improved PCa screening for Vietnam-era veterans. ..
  46. Nukaya M, Moran S, Bradfield C. The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proc Natl Acad Sci U S A. 2009;106:4923-8 pubmed publisher
    ..Given the 100% penetrance of patent DV in Ahr null mice, these results indicate that Cyp1a1 and Cyp1a2 do not play a dominant role in AHR-mediated vascular development. ..
  47. Walisser J, Bunger M, Glover E, Bradfield C. Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development. Proc Natl Acad Sci U S A. 2004;101:16677-82 pubmed
    ..Taken in the broader context, these data demonstrate that similar AHR signaling steps govern all major aspects of AHR biology. ..
  48. Lakhman S, Chen X, Gonzalez Covarrubias V, Schuetz E, Blanco J. Functional characterization of the promoter of human carbonyl reductase 1 (CBR1). Role of XRE elements in mediating the induction of CBR1 by ligands of the aryl hydrocarbon receptor. Mol Pharmacol. 2007;72:734-43 pubmed
    ..These studies provide the first insights on the functional characteristics of the human CBR1 gene promoter. Our data indicate that the AHR pathway contributes to the transcriptional regulation of CBR1. ..
  49. Abnet C, Tanguay R, Hahn M, Heideman W, Peterson R. Two forms of aryl hydrocarbon receptor type 2 in rainbow trout (Oncorhynchus mykiss). Evidence for differential expression and enhancer specificity. J Biol Chem. 1999;274:15159-66 pubmed
    ..These results suggest that the two receptor forms may regulate different sets of genes, and may play different roles in the toxic responses produced by AhR agonists such as TCDD...
  50. Laiosa M, Mills J, Lai Z, Singh K, Middleton F, Gasiewicz T, et al. Identification of stage-specific gene modulation during early thymocyte development by whole-genome profiling analysis after aryl hydrocarbon receptor activation. Mol Pharmacol. 2010;77:773-83 pubmed publisher
    ..These seven genes are novel targets for modulation by the TCDD-activated AHR and may be involved in the observed cell-cycle arrest and suppression of early thymocyte development. ..
  51. Brake P, Jefcoate C. Regulation of cytochrome P4501B1 in cultured rat adrenocortical cells by cyclic adenosine 3',5'-monophosphate and 2,3,7,8- tetrachlorodibenzo-p-dioxin. Endocrinology. 1995;136:5034-41 pubmed
  52. Wang X, Cabrera R, Li Y, Miller D, Finnell R. Functional regulation of P-glycoprotein at the blood-brain barrier in proton-coupled folate transporter (PCFT) mutant mice. FASEB J. 2013;27:1167-75 pubmed publisher
    ..Taken together, these findings strongly suggest that folate deficiency disrupts the BBB function by targeting the transporter and tight junctions, which may contribute to the development of neurological disorders. ..
  53. Everly L, Merrick G, Allen Z, Butler W, Wallner K, Lief J, et al. Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange. Brachytherapy. 2009;8:57-62 pubmed publisher
    ..In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis. ..
  54. Carvalho P, Tillitt D. 2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout. Environ Sci Technol. 2004;38:6300-6 pubmed
    ..Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness. ..
  55. Prasch A, Tanguay R, Mehta V, Heideman W, Peterson R. Identification of zebrafish ARNT1 homologs: 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the developing zebrafish requires ARNT1. Mol Pharmacol. 2006;69:776-87 pubmed
  56. Prasch A, Andreasen E, Peterson R, Heideman W. Interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hypoxia signaling pathways in zebrafish: hypoxia decreases responses to TCDD in zebrafish embryos. Toxicol Sci. 2004;78:68-77 pubmed
    ..Hypoxia decreased TCDD induction of zfCYP1A mRNA, and decreased the potency of TCDD in causing edema. It is not clear whether this is mediated through competition for zfARNT2, or through other mechanisms. ..
  57. Bunger M, Moran S, Glover E, Thomae T, Lahvis G, Lin B, et al. Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor. J Biol Chem. 2003;278:17767-74 pubmed
    ..Taken in sum, these data support a model where most, if not all, of AHR-regulated biology requires nuclear localization. ..
  58. Andreasen E, Spitsbergen J, Tanguay R, Stegeman J, Heideman W, Peterson R. Tissue-specific expression of AHR2, ARNT2, and CYP1A in zebrafish embryos and larvae: effects of developmental stage and 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Toxicol Sci. 2002;68:403-19 pubmed
    ..However, TCDD-induced zfCYP1A expression was not detected in these tissues. Taken together, these results are consistent with the notion that the cardiovascular system is a primary target of TCDD developmental toxicity in zebrafish. ..
  59. Carney S, Chen J, Burns C, Xiong K, Peterson R, Heideman W. Aryl hydrocarbon receptor activation produces heart-specific transcriptional and toxic responses in developing zebrafish. Mol Pharmacol. 2006;70:549-61 pubmed
    ..More than 70% of the transcripts in this heart-specific cluster promote cellular growth and proliferation. Thus, the developing heart stands out as being responsive to TCDD at both the level of toxicity and gene expression. ..
  60. Ikegwuonu F, Jefcoate C. Evidence for the involvement of the fatty acid and peroxisomal beta-oxidation pathways in the inhibition by dehydroepiandrosterone (DHEA) and induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benz(a)anthracene (BA) of cytochrome P4501B1 (CY. Mol Cell Biochem. 1999;198:89-100 pubmed
    ..These results also present evidence for the first time, for the possible peroxisomal effects of TCDD and BA which are similar to those of DHEA in this mouse embryo fibroblast cell line. ..
  61. Singh N, Nagarkatti M, Nagarkatti P. Role of dioxin response element and nuclear factor-kappaB motifs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated regulation of Fas and Fas ligand expression. Mol Pharmacol. 2007;71:145-57 pubmed
    ..Administration of TCDD into mice caused significant increase in Fas and FasL transcripts in thymus and liver. These data demonstrate that TCDD regulates Fas and FasL promoters through DRE and/or NF-kappaB motifs via AhR. ..
  62. Ryan E, Holz J, Mulcahey M, Sheu T, Gasiewicz T, Puzas J. Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. J Bone Miner Res. 2007;22:1571-80 pubmed
    ..These data imply that the AHR mediates the effects of aromatic toxicants on bone and that AHR expression is regulated during osteoblast differentiation. ..
  63. Manikkam M, Tracey R, Guerrero Bosagna C, Skinner M. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS ONE. 2012;7:e46249 pubmed publisher
    ..Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. ..
  64. Davarinos N, Pollenz R. Aryl hydrocarbon receptor imported into the nucleus following ligand binding is rapidly degraded via the cytosplasmic proteasome following nuclear export. J Biol Chem. 1999;274:28708-15 pubmed
    ..These findings show that nuclear export and degradation of the AHR protein are two additional steps in the AHR-mediated signal transduction pathway and suggest novel areas for regulatory control. ..
  65. Pollenz R, Sullivan H, Holmes J, Necela B, Peterson R. Isolation and expression of cDNAs from rainbow trout (Oncorhynchus mykiss) that encode two novel basic helix-loop-Helix/PER-ARNT-SIM (bHLH/PAS) proteins with distinct functions in the presence of the aryl hydrocarbon receptor. Evidence for alternativ. J Biol Chem. 1996;271:30886-96 pubmed
    ..AHR complexes to DNA. In addition, the presence of rtARNTa can reduce the aryl hydrocarbon receptor-dependent function of rtARNTb in vivo and in vitro. ..
  66. Cook P, Robbins J, Endicott D, Lodge K, Guiney P, Walker M, et al. Effects of aryl hydrocarbon receptor-mediated early life stage toxicity on lake trout populations in Lake Ontario during the 20th century. Environ Sci Technol. 2003;37:3864-77 pubmed
  67. Baker T, Peterson R, Heideman W. Early dioxin exposure causes toxic effects in adult zebrafish. Toxicol Sci. 2013;135:241-50 pubmed publisher
    ..Our results show that exposures that produce little if any impact during development can cause severe consequences during adulthood and present a model for studying this process. ..
  68. Lim J, Sanders R, Yeager R, Millsap D, Watkins J, Eells J, et al. Attenuation of TCDD-induced oxidative stress by 670 nm photobiomodulation in developmental chicken kidney. J Biochem Mol Toxicol. 2008;22:230-9 pubmed publisher
    ..The results of this study suggest that 670 nm photobiomodulation may be useful as a noninvasive treatment for renal injury resulting from chemically induced cellular oxidative and energy stress. ..
  69. Hill A, Bello S, Prasch A, Peterson R, Heideman W. Water permeability and TCDD-induced edema in zebrafish early-life stages. Toxicol Sci. 2004;78:78-87 pubmed
    ..In conclusion, TCDD exposure may inhibit the function of a permeability barrier to water, which is critical for maintaining osmotic balance in early development. ..
  70. Nukaya M, Walisser J, Moran S, Kennedy G, Bradfield C. Aryl hydrocarbon receptor nuclear translocator in hepatocytes is required for aryl hydrocarbon receptor-mediated adaptive and toxic responses in liver. Toxicol Sci. 2010;118:554-63 pubmed publisher
  71. Xu C, Krager S, Liao D, Tischkau S. Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci. 2010;115:98-108 pubmed publisher
    ..Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants. ..
  72. Dinatale B, Murray I, Schroeder J, Flaveny C, Lahoti T, Laurenzana E, et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci. 2010;115:89-97 pubmed publisher
    ..Our findings have established that KA is a potent AHR endogenous ligand that can induce IL6 production and xenobiotic metabolism in cells at physiologically relevant concentrations. ..
  73. Flaveny C, Murray I, Perdew G. Differential gene regulation by the human and mouse aryl hydrocarbon receptor. Toxicol Sci. 2010;114:217-25 pubmed publisher
  74. Chen J, Carney S, Peterson R, Heideman W. Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart. Physiol Genomics. 2008;33:148-58 pubmed publisher
    ..Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcriptional repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA. ..
  75. Allgeier S, Lin T, Moore R, Vezina C, Abler L, Peterson R. Androgenic regulation of ventral epithelial bud number and pattern in mouse urogenital sinus. Dev Dyn. 2010;239:373-85 pubmed publisher
    ..Complete VB agenesis by the selective budding inhibitor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) required high androgen signaling. ..
  76. Lin T, Rasmussen N, Moore R, Albrecht R, Peterson R. 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits prostatic epithelial bud formation by acting directly on the urogenital sinus. J Urol. 2004;172:365-8 pubmed
  77. Jackson D, Li H, Mitchell K, Joshi A, Elferink C. Ah receptor-mediated suppression of liver regeneration through NC-XRE-driven p21Cip1 expression. Mol Pharmacol. 2014;85:533-41 pubmed publisher
    ..The evidence also suggests that AhR functionality following partial hepatectomy is dependent on a p21(Cip1)-regulated signaling process, intimately linking AhR biology to the G1-phase cell cycle program. ..
  78. Korza G, Ozols J. Complete covalent structure of 60-kDa esterase isolated from 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rabbit liver microsomes. J Biol Chem. 1988;263:3486-95 pubmed
    ..There is also a close homology between the 60-kDa esterase and the COOH-terminal domain of bovine thyroglobulin. ..
  79. Savas U, Carstens C, Jefcoate C. Biological oxidations and P450 reactions. Recombinant mouse CYP1B1 expressed in Escherichia coli exhibits selective binding by polycyclic hydrocarbons and metabolism which parallels C3H10T1/2 cell microsomes, but differs from human recombinant CYP1B1. Arch Biochem Biophys. 1997;347:181-92 pubmed
    ..This data establishes CYP1B1 as an important contributor to activation of PAHs, particularly in extra hepatic tissues that are susceptible to cancer where CYP1B1 in contrast to CYP1A1 is constitutively expressed. ..
  80. Alexander D, Eltom S, Jefcoate C. Ah receptor regulation of CYP1B1 expression in primary mouse embryo-derived cells. Cancer Res. 1997;57:4498-506 pubmed
    ..We conclude that CYP1B1 expression, including induction via the AhR, parallels a proliferative state for MEF cells. ..
  81. Valdez K, Shi Z, Ting A, Petroff B. Effect of chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats on ovarian gene expression. Reprod Toxicol. 2009;28:32-7 pubmed publisher
    ..Taken together with past studies indicating a lack of effect on hypothalamus or pituitary function, the apparent regulation of key ovarian genes support the hypothesis that chronic TCDD exposure directly affects ovarian function. ..
  82. Vezina C, Hardin H, Moore R, Allgeier S, Peterson R. 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits fibroblast growth factor 10-induced prostatic bud formation in mouse urogenital sinus. Toxicol Sci. 2010;113:198-206 pubmed publisher
  83. Antkiewicz D, Peterson R, Heideman W. Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2006;94:175-82 pubmed
  84. Kerkvliet N, Shepherd D, Baecher Steppan L. T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD. Toxicol Appl Pharmacol. 2002;185:146-52 pubmed
    ..These results indicate that direct AhR-dependent effects of TCDD occur in both CD4+ and CD8+ T cell subsets and both T cell subsets contribute to the full suppression of the CTL response by TCDD. ..
  85. Singh N, Singh U, Singh B, Price R, Nagarkatti M, Nagarkatti P. Activation of aryl hydrocarbon receptor (AhR) leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis. PLoS ONE. 2011;6:e23522 pubmed publisher
    ..These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation. ..
  86. Carney S, Peterson R, Heideman W. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activation of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a CYP1A-independent mechanism in zebrafish. Mol Pharmacol. 2004;66:512-21 pubmed
    ..This suggests an alternative model in which TCDD-activated AHR/ARNT disrupts the normal process of growth and development by altering programs of gene expression or function. ..
  87. Prasch A, Heideman W, Peterson R. ARNT2 is not required for TCDD developmental toxicity in zebrafish. Toxicol Sci. 2004;82:250-8 pubmed
    ..These results demonstrate that zfARNT2 is not essential for mediating TCDD developmental toxicity in zebrafish and suggest that alternate dimerization partner(s) exist for zfAHR2 in vivo. ..
  88. Goodale B, La Du J, Bisson W, Janszen D, Waters K, Tanguay R. AHR2 mutant reveals functional diversity of aryl hydrocarbon receptors in zebrafish. PLoS ONE. 2012;7:e29346 pubmed publisher
  89. Yeager R, Reisman S, Aleksunes L, Klaassen C. Introducing the "TCDD-inducible AhR-Nrf2 gene battery". Toxicol Sci. 2009;111:238-46 pubmed publisher
    ..Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice. ..