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A Study of Polynuclear Aromatic Hydrocarbon Carcinogen Transport and Deoxyribonucleic Acid RepairJoe, Cheol O., 1949- 12 1900 (has links)
This investigation addresses the interrelated problems of A) Uptake and vascular transport of lipophilic chemical carcinogens, and intracellular interactions between lipoproteins and carcinogens; B) Biochemical mechanisms by which polynuclear aromatic hydrocarbon carcinogens inhibit the replicative and repair DNA synthesis in cells. The results observed in this study suggest that ingested benzo(a)pyrene (BaP) enters the gastrointestinal lymphatic drainage sequestered within lymphatic lipoproteins, and that low-density lipoproteins (LDL) play a major role in the vascular transport of BaP. BaP is taken up into cells by adsorptive endocytosis mediated by an interaction between apolipoprotein-specific receptors on the cell membrane and the specific apolipoproteins on LDL. Having entered peripheral cells sequestered within the lipid core of LDL, an electrophilic metabolite of BaP covalently binds to cellular DNA, and may interact with other cellular macro-molecules. Data presented here suggest that LDL is also absolutely required for the activation of DNA polymerase-a, which is the major enzyme of DNA excision repair necessary to correct the DNA damage caused by BaP. This study concludes that an active metabolite of the polynuclear aromatic hydrocarbon carcinogen, benzo(a)pyrene, suppresses DNA polymerase-a activity by inhibiting the binding of 2'-deoxyguanosine 5'-triphosphate to an acceptor site on the DNA polymerase-a complex with the DNA substrate, thereby competitively inhibiting interaction of 2'-deoxyguanosine 5'-triphosphate in the DNA synthetic process.
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Development of a murine model of venous thrombosis in chronic kidney disease and targeted therapy by aryl hydrocarbon receptor inhibitionSellinger, Isaac Emanuel 08 March 2024 (has links)
Chronic kidney disease (CKD) is a common disease that affects millions across the US and the globe. Patients with CKD experience an increased risk of venous thrombosis. Here we use two longstanding robust murine models of nephropathies in conjunction with a reliable murine model of venous thrombosis to model venous thrombosis risk in CKD. We show that in the adenine diet-induced CKD, increased concentrations of adenine in the diet result in increased histological evidence of nephropathy and increased venous thrombosis risk assessed by Inferior Vena Cava ligation. Next, we demonstrate that in unilateral ureteric obstruction models, the duration of obstruction is proportional to the nephropathies developed by histological assessment. In both models, we relate nephropathy to venous thrombosis risk. When probed for aryl hydrocarbon receptor (AHR) activation, adenine diet-induced CKD mice show increased activation assessed by nuclear translocation of the receptor. This phenotype was confirmed in vitro when treating human telomerase immortalized human umbilical endothelial cells with uremic serum. Nuclear AHR was not observed in control conditions in vivo or in vitro. Pharmacologic AHR inhibition using a novel drug, BAY Compound, and a well-known AHR inhibitor were both able to abrogate uremic activation of AHR in vitro, which was then corroborated with in vivo studies. Tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) are prothrombogenic proteins linked to AHR activation. TF and PAI-1 showed upregulation in CKD mice which were blocked when CKD mice were given AHR inhibitor BAY Compound. This work demonstrates a unique model of venous thrombosis in CKD and suggests that AHR inhibition may be able to limit the elevated risk of venous thrombosis associated with uremia. / 2026-03-08T00:00:00Z
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USE OF REMOTE SENSING AND GEOPHYSICAL TECHNIQUES FOR LOCATING ABANDONED OIL WELLS, WOOD COUNTY, OHIOBorton, TiffanyAnn 30 March 2007 (has links)
No description available.
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Global Combustion Responses of Practical Hydrocarbon Fuels: <i>n</i>-Heptane, <i>iso</i>-Octane, <i>n</i>-Decane, <i>n</i>-Dodecane and EthyleneKumar, Kamal 25 January 2007 (has links)
No description available.
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THE DEVELOPMENT, EVALUATION AND APPLICATION OF A PHYSIOLGICALLY-BASED TOXICOKINETIC MODEL FOR FLUORANTHENE IN RAINBOW TROUT (Onchorhyncus mykiss)Smith, Carrie Anne 07 November 2003 (has links)
No description available.
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ROLE OF THE AHR IN POLYBROMINATED BIPHENYL-INDUCED DEVELOPMENTAL TOXICITYMILLER, KEVIN ANTHONY January 2003 (has links)
No description available.
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Contamination of Firefighter Personal Protective GearAlexander, Barbara M. 17 September 2012 (has links)
No description available.
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TCDD-induced modulation of the hs1,2 enhancer within the 3’immunoglobulin heavy chain regulatory regionFernando, Tharu M. January 2009 (has links)
No description available.
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Aryl Hydrocarbon Receptor-Mediated Regulation of Gene Expression during Cardiomyocyte DifferentiationWang, Qin 11 September 2015 (has links)
No description available.
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Applying the Principle of Corresponding States to Multi-component Hydrocarbon Mixtures (Jet Fuels)Evanhoe, Matthew January 2015 (has links)
No description available.
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