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Articles 1 - 9 of 9
Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White
Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White
Browse all Theses and Dissertations
The 3'IGHRR is thought to be responsible for the transcription of the immunoglobulin heavy chain (IGH) gene locus, which is essential for the production of antibodies. The human 3’IGHRR, which is duplicated in humans, contains the hs3, hs4, and hs1.2 enhancers. Additionally, the hs1.2 enhancer is polymorphic in humans and consists of a 53 bp invariant sequence that can be repeated one to four times. Previous experiments in a mouse and human B-cell line model have shown that the high affinity AhR ligand and environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce hs1.2 enhancer activity in an AhR-dependent manner. The AhR is …
Characterizing The Impacts Of Contaminants On Fish Embryogenesis And Revealing An Alternate Molecular Mechanism Of Ahr Mediated Cardiac Defects, Corinna Singleman
Characterizing The Impacts Of Contaminants On Fish Embryogenesis And Revealing An Alternate Molecular Mechanism Of Ahr Mediated Cardiac Defects, Corinna Singleman
Dissertations, Theses, and Capstone Projects
There is a long history of damage to natural ecosystems from environmental pollution. Many environmental contaminants are man-made and have been released with abandon over the last 100 years including dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyls (PCBs). These chemicals act on similar cellular processes and cause skin lesions, cancer, learning disabilities and reproductive problems in many vertebrates. There are many studies exploring various aspects of TCDD and PCB exposure on model and wild organisms. Few studies however, have compared effects of PCB mixtures on ecosystems to effects of individual PCBs in the lab. The first aim of this thesis is …
Impact Of Gestational Exposure To 2,3,7,8-Tetrachlorodibenzo-P-Dioxin On T Lymphocyte Development, Lori S. Ahrenhoerster
Impact Of Gestational Exposure To 2,3,7,8-Tetrachlorodibenzo-P-Dioxin On T Lymphocyte Development, Lori S. Ahrenhoerster
Theses and Dissertations
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant and the best characterized agonist of the arylhydrocarbon receptor (AHR), a transcription factor crucial to the detoxification of numerous xenobiotics. Studies in animals show that TCDD is immunosuppressive in adult exposures, and epidemiological studies have found an association between TCDD exposure and hematologic cancers. Additionally, developmental exposure to TCDD has been shown to increase the likelihood of autoimmunity and to impair immune response to later-life infections. The cells of the immune system are all descended from multipotent hematopoietic stem cells (HSCs) that originate in the fetus. This multipotency, defined as the ability to …
The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms
The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms
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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study utilized an IgA secreting mouse …
Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs
Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs
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Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …
2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis
2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis
Browse all Theses and Dissertations
2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent toxin which inhibits the antibody response of B cells. The 3'IgHRR which is involved in transcriptional regulation of the heavy-chain polypeptide of antibodies is inhibited by TCDD. The hs1,2 enhancer region, isolated from the 3'IgHRR, is also inhibited while the isolated hs4 is activated by TCDD. This project sought to determine if that dichotomy in effects results from interactions at enhancer-specific binding sites for AhR, thought to mediate transcriptional effects of TCDD, and NFκB, a transcription factor involved in B cell activation. Here, I report a difference in the effect of TCDD on transcriptional activity …
Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando
Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando
Browse all Theses and Dissertations
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin that inhibits immunoglobulin (Ig) gene expression in mice. Transcriptional regulation of the Ig heavy chain (IgH) involves the 3'IgH regulatory region (3'IgH RR). The murine 3'IgH RR consists of four enhancers (hs3A, hs1,2, hs3B, and hs4), which are homologous to the human 3'IgH RR enhancers (hs3, hs1,2, and hs4). In humans, a polymorphism of the hs1,2 enhancer, resulting in a varying number of tandem repeats of a 53 bp sequence, has been correlated with autoimmune diseases like IgA nephropathy and Celiac disease. The repeated sequence contains a kB and DRE binding site. Previous …
2,3, 7,8-Tetrachlorodibenzo-P-Dioxin, Steven P. Bradbury
2,3, 7,8-Tetrachlorodibenzo-P-Dioxin, Steven P. Bradbury
Steven P. Bradbury
Since 1985, the United States Environmental Protection Agency (USEPA) has classified 2,3,7,8-tetrachloro-p-dioxin (TCDD) as a probable human carcinogen; subsequently, sources of TCDD in the environment have been regulated on the basis of animal cancer rates extrapolated to doses associated with human exposures. Two major activities have prompted the decision to reassess this approach for evaluating TCDD toxicity and its associated risks. First, an epidemiological study of cancer mortality in U.S. chemical workers by the National Institute of Occupational Safety and Health provided evidence of TCDD-mediated human carcinogenicity (Fingerhut et al. 1991 ). Second, at a 1990 Banbury conference a consensus …
Interim Report On Data And Methods For Assessment Of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Risks To Aquatic Life And Associated Wildlife, Steven P. Bradbury, Philip M. Cook, Russell J. Erickson, Robert L. Spehar, Gerald T. Ankney
Interim Report On Data And Methods For Assessment Of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Risks To Aquatic Life And Associated Wildlife, Steven P. Bradbury, Philip M. Cook, Russell J. Erickson, Robert L. Spehar, Gerald T. Ankney
Steven P. Bradbury
In April, 1991 the Administrator of the U.S. Environmental Protection Agency (EPA) announced that the Agency would conduct a scientific reassessment of the risk of 2,3,7,8-tetrachlorodibenzo-p-dioxin (hereafter referred to as TCDD), and similar chemicals, to human health and the environment. Since 1985, EPA has classified TCDD, which it considers the most potent known animal carcinogen, as a probable human carcinogen. Sources of TCDD in the environment were subsequently regulated on the basis of animal cancer rates extrapolated to doses associated with human exposures. Recently, consensus has developed that the toxic effects of TCDD appear to be mediated by its binding …