Spelling suggestions: "subject:"chlorinated biphenyls (PCBs)""
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THE ROLE OF NF-kB ACTIVATION IN HEPATIC TUMOR PROMOTION BY POLYCHOLORINATED BIPHENYLS (PCBs)Lu, Zijing 01 January 2002 (has links)
Polychlorinated biphenyls (PCBs) are nongenotoxic hepatic tumor promoters. PCBs have been shown to cause oxidative stress, but the exact mechanism by which PCBs exert their tumor promoting activity is not clear. In our study, PCB-153, a non-coplanar congener, caused a transient increase in hepatic NF-B DNA binding activity and cell proliferation, while PCB-77, a coplanar congener, showed no effect. Our second study using a mouse model that was deficient in the p50 subunit of NF-kB (p50-/-) showed that NF-kB contributes to the changes in hepatocyte proliferation and apoptosis in response to PCB-153 treatment: a single dose of PCB-153 increased hepatic NF-B activity and cell proliferation in wild type mice, but not in the p50-/- mice; longer-term treatment with PCB-153 increased cell proliferation in p50-/- mice, but this increase was less than that in the wild type. In addition, p50-/- livers had more apoptosis than in the wild type, and PCB-153 inhibited apoptosis in the p50-/- livers. p50-/- livers had less cyclin D1 protein than the wild type, but that the mRNA levels were same. Bcl-xL protein was not changed by PCB-153, and wild type and p50-/- mice had the same level of Bcl-xL protein. In the third study, PCB-77 caused an increase in hepatic NF-kB DNA binding activity and cell proliferation during the promotion stage, and this increase was blocked by dietary supplementation of vitamin E, but the number and volume of placental glutathione S-transferase (PGST)-positive foci were slightly, though insignificantly, increased in the same animals. The apparent conflict could be due to different effect in different cells: high level vitamin E significantly inhibited PCB-77-induced cell proliferation in normal hepatocytes, while this inhibitory effect was much less in the PGST-positive hepatocytes. In conclusion, our studies show that a non-coplanar PCB can cause an increase in hepatic NF-kB DNA binding activity in rats and mice, and this increase contributes to the change in cell proliferation and apoptosis. Dietary vitamin E supplementation did not show protective effect on the formation of altered hepatic foci that were promoted by PCBs, although vitamin E supplementation decreased PCBs-induced hepatic NF-kB activation and cell proliferation.
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Integrative analysis of endocrine-disrupting chemical effects in the developing hypothalamus : adult behaviors and neural networksTopper, Viktoria Yuryevna 12 August 2015 (has links)
Endocrine-disrupting chemicals (EDCs) are environmental pollutants known to perturb hormone systems and interfere with normal endocrine function. Exposure to EDCs during hormone-sensitive developmental periods can result in profound dysfunction in reproductive physiology and behavior. In this dissertation, effects of gestational exposure to a class of EDCs called polychlorinated biphenyls (PCBs) were examined in the developing hypothalamus, which is known to control reproductive physiology and behavior in vertebrates. The specific hypothesis was that PCBs caused changes in sexually dimorphic hypothalamic nuclei, resulting in perturbation of adult sociosexual behaviors and alteration of neural networks with changes in expression of microRNAs and genes during development and in adulthood.
This research focused on two brain areas relevant to understanding the PCB effects on the developing hypothalamus: 1) microRNA and related target gene expression during postnatal development, 2) adult sociosexual behaviors and gene expression. In both sections, molecular changes were examined in two sexually dimorphic hypothalamic nuclei, medial preoptic nucleus (MPN) and ventromedial nucleus (VMN), known for their role in regulation of sociosexual behavior. In the first section of the dissertation, the effects of PCBs were examined on the expression of microRNAs and target genes at four ages during postnatal [P] development (P15, P30, P45, and P90). Age and sex specific effects were observed in both MPN and VMN, with greater effects in the MPN. The second research section of the dissertation explored whether sociosexual behaviors, namely ultrasonic vocalizations and sociosexual preference behaviors, were altered by gestational PCBs. Expression of forty-eight neuroendocrine candidate genes was also examined in the MPN and VMN of the same animals. Several sociosexual behaviors were affected, including number and acoustic properties of ultrasonic vocalizations, and nose-touching with opposite-sex animals. Gene expression was altered in sex and region-specific manner in the brains of behaviorally affected rats. Taken together, these findings suggest that gestational PCBs have lasting effects on molecular mechanisms during postnatal development and in adulthood, and could result in altered sociosexual behavior. These results have implications for human health and disease, as early life exposures to EDCs have been linked to reproductive decline in humans. / text
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USE OF IN-SITU FISH POPULATIONS FOR BIOMONITORING POLYCHLORINATED BIPHENYL AND METAL POLLUTION IN MODERATELY IMPACTED FRESHWATER STREAMSPrice, David John 01 January 2007 (has links)
Water, sediments, floodplain soils, and fish from Big and Little Bayou creeks were assessed for polychlorinated biphenyls (PCBs) and metals in 1987-2005. The streams were impacted by effluents from the Paducah Gaseous Diffusion Plant (PGDP). PCBs were rarely detected in water samples. Aroclor 1248 detections in sediments and floodplains were sporadic, but 1254 and 1260 were consistent. Seasonal variations were only observed for Aroclor 1248. Detection of PCBs in floodplains indicated recent influx of contaminated sediments. Species-specific PCB residues patterns were studied for Lepomis cyanellus, L. megalotis, L. macrochirus, and Campostoma anomalum. Highest PCB concentrations were found in stoneroller minnows. PCBs decreased over time in sunfish species, but retained a baseline level. No relationships were found between sunfish age and PCB concentrations. At low PCB levels, green sunfish body burden (BB) did not correlate with lipid content. A certain PCB concentration must be exceeded before PCB BB correlates with lipid content. Stream flows differed by season, and fish PCB BB differed by season, but stream flow did not correlate with fish BB. Congener groups corresponded to Aroclor concentrations. Higher chlorinated biphenyls peaked in the spring for sport fish. PCBs remobilized in the spring resulted in higher summer BB for the stoneroller minnows, whereas sunfish eliminated PCBs by summer. This variability was due to the sunfishs ability to regulate PCBs. Metal concentrations did not display the seasonal variability evident in the PCB data. Water metals may have peaked during storm events and decreased rapidly. Water Pb increased with time, but the source could not determined. Zinc in Little Bayou creek likely originated from the PGDP. Except for Cu and Zn, stoneroller minnow metal BB decreased with time. Metal BB were used to determine bioavailable fractions. Less than half of the water column Cd, Cr, Fe, and Pb in impacted areas were bioavailable to stoneroller minnows, whereas 59% of Ag, 73% of Cu, and 64% of Zn were bioavailable. Cumulative criterion units were calculated to determine additive metal impacts, and proved useful in locating sectors with possible ecological impact. In-situ monitors proved valuable in studying PCB and metal behavior under real-world conditions.
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An evaluation of the distributions of polychlorinated biphenyls and organic matter in coastal sedimentsJönsson, Anders January 2004 (has links)
<p>The objective of this thesis is to improve the understanding of what processes and mechanism affects the distribution of polychlorinated biphenyls (PCBs) and organic carbon in coastal sediments. Because of the strong association of hydrophobic organic contaminants (HOCs) such as PCBs with organic matter in the aquatic environment, these two entities are naturally linked. The coastal environment is the most complex and dynamic part of the ocean when it comes to both cycling of organic matter and HOCs. This environment is characterised by the largest fluxes and most diverse sources of both entities. A wide array of methods was used to study these processes throughout this thesis. In the field sites in the Stockholm archipelago of the Baltic proper, bottom sediments and settling particulate matter were retrieved using sediment coring devices and sediment traps from morphometrically and seismically well-characterized locations. In the laboratory, the samples have been analysed for PCBs, stable carbon isotope ratios, carbon-nitrogen atom ratios as well as standard sediment properties. From the fieldwork in the Stockholm Archipelago and the following laboratory work it was concluded that the inner Stockholm archipelago has a low (≈ 4%) trapping efficiency for freshwater-derived organic carbon. The corollary is a large potential for long-range waterborne transport of OC and OC-associated nutrients and hydrophobic organic pollutants from urban Stockholm to more pristine offshore Baltic Sea ecosystems.</p><p>Theoretical work has been carried out using Geographical Information Systems (GIS) and statistical methods on a database of 4214 individual sediment samples, each with reported individual PCB congener concentrations. From this work it was concluded that the continental shelf sediments are key global inventories and ultimate sinks of PCBs. Depending on congener, 10-80% of the cumulative historical emissions to the environment are accounted for in continental shelf sediments. Further it was concluded that the many infamous and highly contaminated surface sediments of urban harbours and estuaries of contaminated rivers cannot be of importance as a secondary source to sustain the concentrations observed in remote sediments. Of the global shelf PCB inventory < 1% are in sediments near population centres while ≥ 90% is in remote areas (> 10 km from any dwellings). The remote sub-basin of the North Atlantic Ocean contains approximately half of the global shelf sediment inventory for most of the PCBs studied.</p>
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Hydroxylated and sulfated metabolites of lower chlorinated PCBs bind with high affinity to human serum albumin and exhibit selective toxicity to neuronal cellsRodriguez, Eric Alberto 01 May 2016 (has links)
Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been associated with a myriad of negative human health effects. These man-made compounds were used throughout most of the 20th century and although their intentional production has since been banned and their use limited to closed systems, their prevalence in the environment remains a factor in disease states for exposed populations. The worldwide levels of PCBs has been declining, however, there is evidence for renewed sources of these compounds. The presence of PCBs with lower numbers of chlorine atoms (LC-PCBs) have been verified as unintentional byproducts in paints and pigments, the decomposition of PCB waste, or the recycling or disposal attempts of PCB-laden materials. While exposure to the higher chlorinated congeners (HC-PCBs) is often attributed to the consumption of contaminated water or fatty animal meat, a significant route of exposure to the airborne LC-PCBs is through inhalation. These semi-volatile compounds have been detected in high quantities in both indoor and outdoor air in urban and rural communities, and their presence is pronounced in older buildings (e.g., homes and schools). When compared to HC-PCBs, LC-PCBs are more highly susceptible to metabolic transformations, and recently their sulfated metabolites have gained much interest. Although the sulfation of xenobiotics often is considered a route for their removal from the body, a previous study of Sprague-Dawley rats treated with 4-chlorobiphenyl (PCB 3) resulted in the substantial formation of sulfated metabolites (i.e., hydroxylation followed by sulfation of the LC-PCB). This metabolic route accounted for more than half of the treatment dose. Furthermore, LC-PCB sulfates have been shown to bind to the human serum protein, transthyretin, in vitro.
Of the health effects associated with PCB exposure, neurotoxicity has been well established through various laboratory and epidemiological studies. It is proposed that the dopaminergic system lies at the core of the observed cognitive, motor, and intellectual dysfunction observed in exposed populations, especially in children exposed perinatally. Interestingly, PCB exposure has been linked to Parkinson's disease (PD) etiology, which is marked by a substantial loss of dopaminergic neurons.
This thesis describes studies on the binding of selected LC-PCBs and their hydroxylated and sulfated metabolites to human serum albumin (HSA), the most abundant protein in human serum. The displacement of fluorescent probes, selective for the two major drug binding sites of HSA, indicates that LC-PCB sulfates generally bind to HSA with such affinity that is equal to or greater than that for the LC-PCBs or OH-LC-PCBs This work also included a study of the selective toxicity of these compounds to dopaminergic neuronal cells. The selective toxicity of these compounds was studied in a series of immortalized cell lines (i.e., two neuronal cell lines: the rat midbrain-derived N27 cell line, the human neuroblastoma-derived SH-SY5Y cell line, and the human liver-derived HepG2 cell line). The assessment of toxicity by MTT reduction and LDH release in these cellular models indicated that hydroxylated and sulfated metabolites of LC-PCBs exhibited toxicity that was selective to neuronal cells and, in most cases, selective for the dopaminergic neuronal cells. Furthermore, HPLC analysis of the distribution of the compounds from the extracellular medium into the cellular milieu indicated that the observed toxicity may be due in some cases to selective transport and further metabolism. This work contributes to understanding the neurotoxicity of LC-PCB hydroxylated and sulfated metabolites and the role that binding to serum proteins may play in it. Furthermore, it emphasizes the need for future studies on the effects that metabolism, particularly sulfation, may play in the disposition of LC-PCB congeners as it pertains to their metabolism, retention, and toxic effects.
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An evaluation of the distributions of polychlorinated biphenyls and organic matter in coastal sedimentsJönsson, Anders January 2004 (has links)
The objective of this thesis is to improve the understanding of what processes and mechanism affects the distribution of polychlorinated biphenyls (PCBs) and organic carbon in coastal sediments. Because of the strong association of hydrophobic organic contaminants (HOCs) such as PCBs with organic matter in the aquatic environment, these two entities are naturally linked. The coastal environment is the most complex and dynamic part of the ocean when it comes to both cycling of organic matter and HOCs. This environment is characterised by the largest fluxes and most diverse sources of both entities. A wide array of methods was used to study these processes throughout this thesis. In the field sites in the Stockholm archipelago of the Baltic proper, bottom sediments and settling particulate matter were retrieved using sediment coring devices and sediment traps from morphometrically and seismically well-characterized locations. In the laboratory, the samples have been analysed for PCBs, stable carbon isotope ratios, carbon-nitrogen atom ratios as well as standard sediment properties. From the fieldwork in the Stockholm Archipelago and the following laboratory work it was concluded that the inner Stockholm archipelago has a low (≈ 4%) trapping efficiency for freshwater-derived organic carbon. The corollary is a large potential for long-range waterborne transport of OC and OC-associated nutrients and hydrophobic organic pollutants from urban Stockholm to more pristine offshore Baltic Sea ecosystems. Theoretical work has been carried out using Geographical Information Systems (GIS) and statistical methods on a database of 4214 individual sediment samples, each with reported individual PCB congener concentrations. From this work it was concluded that the continental shelf sediments are key global inventories and ultimate sinks of PCBs. Depending on congener, 10-80% of the cumulative historical emissions to the environment are accounted for in continental shelf sediments. Further it was concluded that the many infamous and highly contaminated surface sediments of urban harbours and estuaries of contaminated rivers cannot be of importance as a secondary source to sustain the concentrations observed in remote sediments. Of the global shelf PCB inventory < 1% are in sediments near population centres while ≥ 90% is in remote areas (> 10 km from any dwellings). The remote sub-basin of the North Atlantic Ocean contains approximately half of the global shelf sediment inventory for most of the PCBs studied.
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Concentrations and distribution of polycyclic aromatic hydrocarbons(PAHs) and polychlorinated biphenyls(PCBs) in Kaohsiung HarborChen, kai-ting 18 March 2010 (has links)
This study investigated the concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the particulate and dissolved phase, as well as concentrations of PAHs in the sediment in Kaohsiung Harbor lagoon. Sources of PAHs in the water column were determined by isomer ratios, hierarchical cluster analysis (HCA) and principal components analysis (PCA). The net and annual fluxes of PAHs were calculated after a lagoon-wide water sampling campaign and compared with those found in a previous study (Fang, 2007) in which data from only one water sampling station was used.
¡@¡@In rain season, total PAH concentrations ranged from 21.6 to 36.2 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 15.5 to 27.2 ng/L and from 3.4 to 8.6 ng/L, respectively. In dry season, total PAH concentrations ranged from 13.2 to 31.5 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 8.0 to 21.1 ng/L and from 5.3 to 10.5 ng/L, respectively. Total PAH concentrations were found higher in rain season than in dry season. The highest total PAH concentration in dry season was observed in Chianjen River estuary. Relatively high PAH concentrations were also observed in these southern stations of Kaohsiung Harbor because of their location near Dalin industrial park. Total PAH concentrations ranged from 81.7 to 2279 ng/g for sediment samples, with average of 895 ng/g.
The correlations between PAH concentrations and organic carbons, water temperature, salinity and suspended particles were also examined in this study. PAH concentration in dissolved phase was negatively correlated with water temperature (p<0.05). PAH concentration in sediment was positively correlated with organic carbons (p<0.05), and negatively correlated with median diameter (p<0.01). The logKoc¡ÐlogKow relationship in rain and dry season was compared with literature. It was found that the logKoc values were higher than those reported in literature, suggesting that soot particles might play an important role in the transport and distribution of PAHs in the study area.
In rain season, PAHs in dissolved phase were mainly from pyrogenic origins; while mainly from petrogenic origins in particulate phase. In contrast, in dry season, PAHs in dissolved phase were mainly from petrogenic origins; while mainly from pyrogenic origins in particulate phase. In addition, it was found, relatively, that petrogenic pollution was introduced maily from the northern area of the lagoon.
In rain season, total PCB concentrations ranged from 1.1 to 2.7 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 0.42 to 2.1 ng/L and from 0.24 to 1.4 ng/L, respectively. In dry season, total PCB concentrations ranged from 0.54 to 1.3 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 0.20 to 0.74 ng/L and from 0.32 to 0.76 ng/L, respectively.
The direction of net fluxes of PAHs in this study are from water to air (net volatilization) in summer. In winter, however, the absorptive PAH fluxes obtained for four to six-ring PAH, such as fluoranthrene, chrysene + triphenylene and benzo[a]anthracene, indicating that PAHs were absorbed into surface waters. According to our results, it was suggested that the results from previous study (Fang, 2007) might underestimate the net fluxes of Pyrene and total fluxes in dry season. The annual fluxes of PAHs estimated in this study were 212 mg/m2 /year and 5.7 kg of PAHs were emitted annually from the harbor lagoon surface waters to the ambient atmosphere.
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Modeling Anaerobic Dechlorination Of Polychlorinated BiphenylsDemirtepe, Hale 01 February 2012 (has links) (PDF)
This study aims to investigate the fate of polychlorinated biphenyls (PCBs) in sediments via using an anaerobic dechlorination model (ADM). PCBs are ubiquitous environmental pollutants, accumulated mostly in aquatic sediments. Significant attention was placed on the anaerobic dechlorination of PCBs since this process leads to the conversion of highly-chlorinated biphenyls to lower chlorinated ones, resulting in less toxic and more biodegradable congeners. An ADM was developed previously for the identification and quantification of anaerobic dechlorination pathways. In the present study, this model was improved and applied to laboratory and environmental sediment PCB data from Baltimore Harbor (BH), Maryland, USA, where PCB contamination has been recorded. The laboratory PCB data was from a 500 day microcosm study conducted with BH sediments which was used to validate the model, as well as to gather information on dominant dechlorination pathways affecting the sediments. ADM predicted the laboratory PCB data almost perfectly and subsequently very well predicted the environmental sediment PCB profiles. A complete identification and quantification of the anaerobic dechlorination pathways occurring in the BH sediments is achieved with this study for the first time. The significant similarity between the sediment sample PCB profiles and the model predicted profiles reveals that the BH sediments have undergone anaerobic dechlorination via a combination of previously identified dechlorination activities (N, P, M) with selective pathways. Model findings are consistent with microbial analysis of the sediments. Better understanding of anaerobic dechlorination mechanisms should aid in predicting natural attenuation of PCBs or developing bioremediation strategies for contaminated sites.
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COPLANAR PCB-INDUCED INFLAMMATION AND DIETARY INTERVENTIONSEske, Katryn Elizabeth 01 January 2013 (has links)
Diseases, such as cardiovascular disease (CVD), are linked to chronic low levels of inflammation. This inflamed state is the product of risk factors including exposure to environmental pollutants, such as polychlorinated biphenyls (PCBs), which are correlated with increased risk for CVD and diabetes. In response to this health risk, our research addresses the mechanisms by which coplanar PCBs elicit an inflammatory response and the mitigation of PCB-induced inflammation through dietary intervention using docosahexaenoic acid (DHA), an omega-3 lipid. Investigators from the University of Kentucky Engineering Department are developing remediation technologies that detoxify PCBs through dechlorination. We studied the cellular toxicity of coplanar PCB 77 remediation products in primary vascular endothelial cells. The dechlorination products elicited different toxicological responses, which were less than the parent compound and contributed to the overall inflammatory response. The presence of PCB 77 at any concentration was sufficient to promote an inflammatory response, which was attenuated with complete dechlorination. PCB 77 is a good model for coplanar PCB-induced toxicity, but in environmental and human samples, coplanar PCB 126 is detected more frequently. Using different doses of PCB 126, we determined that acute exposure to 5 μmol PCB 126/kg mouse was sufficient to produce an inflammatory response without inducing a toxic wasting phenotype. PCB-induced inflammation was attenuated in vitro by DHA-derived neuroprostanes. Applying this information, we fed mice a DHA-enriched diet and exposed them to PCB 126. Liver and adipose lipid profiles confirm an increase in omega-3 fatty acid composition and DHA metabolites, and changes in gene expression indicate a heightened anti-oxidant response in the presence of PCB-induced inflammation. These data provide an overview of the in vivo response to a PCB-induced inflammation after DHA dietary feeding. We have demonstrated that PCB-induced endothelial dysfunction is propagated through lipid domains called caveolae. Caveolae are also signaling domains for toll-like receptor 4 (TLR4), and receptor for lipopolysaccharide (LPS). Similar to PCBs, TLR4 signaling is inhibited by DHA. We compared the caveolae-associated signaling response after exposure to coplanar PCB 126 or LPS. The domain localization of caveolae was altered by both PCB 126 and LPS. Our study determined that PCB 126-induced inflammation was not inhibited by a TLR4-specific inhibitor, but caveolae-based signaling was critical to both PCB 126- and LPS-induced inflammation. Environmental pollutants, such as coplanar PCBs, are risk factors in the development of chronic diseases. Here we investigate possible signaling pathways associated with environmental toxicity and apply potential dietary interventions with omega-3 lipids.
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A Report on Internships at Donovan Law and Federated Department Stores, IncHalfhill, Andrew James 31 March 2005 (has links)
No description available.
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