Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 99-111).

Thesis (M.S.) in Civil Engineering--University of Maine, 2002. / Includes vita. Includes bibliographical references (leaves 76-85).

Lymphomas are malignant diseases involving the lymphatic system. Arsenic trioxide (As2O3) is a current therapeutic agent for acute promyelocytic leukaemia (APL).APL cells are sensitive to As2O3, with As2O3directly targeting the PML-RARA protein that plays an important role in the oncogenesis of APL. In order to discover the potential of As2O3as a treatment of lymphoma, understanding of the molecular mechanism of As2O3in human lymphoma cells is essential. In this thesis, we showed that the MYC gene is a therapeutic target for As2O3in B-cell lymphomas and the CCND1 (cyclin D1) gene is another therapeutic target for As2O3in mantle cell lymphoma (MCL), a subtype of non-Hodgkin lymphoma (NHL). Both real-time RT-PCR and immunoblotting analysis showed that the expression levels of MYC in all B-cell lymphoma cell lines were down-regulated at both mRNA and protein level after As2O3treatment. The expression levels of MYC were also found to positively correlate with the arsenic sensitivity as measured by MTT assay. Hence, the higher the level of MYC expression, the higher the arsenic sensitivity of human B-cell lymphoma cell lines. Besides, the change of downstream genes after modulation of MYC expression level by As2O3 treatment was investigated. The expression level of CDKN1A and CDKN1B was increased after As2O3 treatment. Interestingly, the growth rate of MYC over-expressing lymphoma cell lines decreased significantly after As2O3treatment, while there was no significant decrease in colony formation assay in lymphoma cells without MYC over-expression. Immunoblotting analysis showed that As2O3could degrade the cyclin D1 protein in mantle cell lymphoma cell lines in a dose-dependent manner. Real-time RT-PCR analysis also showed that the mRNA level of CCND1gene was decreased after As2O3treatment. We also demonstrated that As2O3-induced cyclin D1 protein degradation was related to the proteasome pathway. The growth rate of MCL cell line decreased significantly after As2O3treatmentby using colony formation assay. Human water channel protein, aquaporin 9 (AQP9) has been demonstrated to facilitate the arsenic uptake in human leukaemia cells. In this thesis, we showed that the expression levels of AQP9were found to positively correlate with the arsenic sensitivity as measured by MTT assay in B-cell lymphoma cells. We also demonstrated that dexamethasone could up-regulate AQP9expressions at both mRNA and protein levels in human B-cell lymphoma cell lines. These results not only suggest that As2O3is a potential therapy for B-cell lymphomas, especially for those MYC-over-expressed B-cell lymphomas and MCL, but also indicate that MYC may act as a biomarker for predicting the clinical behaviour of B-cell lymphoma patients to the As2O3treatment.Moreover, dexamethasone pre-treatment may enhance the therapeutic effect of As2O3by up-regulating AQP9expression in B-cell lymphomas. / published_or_final_version / Medicine / Master / Master of Philosophy

Selenium and arsenic are important metalloids in the food chain from nutritional and toxicological point of view. These two metalloids are potentially enriched through geogenic processes and anthropogenic activities and they could sometimes co-exist in nature and become available to plants thereby entering the food chain. While selenium is known as an essential element to humans, it could also be toxic. Arsenic on the other hand is a potentially toxic element posing serious health risks to livestock and humans. They have been found to neutralise each other’s effects in animals but their interactions in plants are not well understood. Speciation analysis, which is a set of activities leading to identification and quantification of different forms or species of elements present in an entity, is required for a holistic understanding of the mechanisms and interactions involved in the plants’ metabolism of contaminants and essential elements. Many techniques are currently being used for speciation of selenium and arsenic in plants and they sometimes give contradictory outcomes. The hyphenation of HPLC with MS and synchrotron techniques are the two most commonly used state of the art techniques for speciation of these metalloids. This research therefore sought to access, explore and/ or develop analytical methods appropriate for the speciation of selenium and arsenic in plants. Many selenium and arsenic species have been identified and reported in the literature using well established procedures. The presence of elemental selenium in plants has also been widely reported in plants but to our knowledge this presence has never been experimentally proven and fully quantified. Because this species is non toxic, its proven occurrence in plants will represent a potential detoxification mechanism. Therefore in this study, a method was specifically developed for identification and quantification of elemental selenium. In order to investigate the occurrence of elemental selenium in plants, the newly developed method was applied using Thunbergia alata as a model plant. Arsenic is known to activate the synthesis of PC using glutathione and the complexation of the activating arsenic ions with the synthesised PCs is a well established detoxification mechanism for arsenic. However, very little is known about the role of glutathione and PCs in selenium detoxification. In order to be able to gain better insight into the interaction between selenium and arsenic in plants, the role of glutathione and PCs in selenium metabolism was investigated using Arabidopsis thaliana as a model plant. Sensitivity tests and speciation analysis were carried out on Arabidopsis thaliana WT and the mutants’ one of which is deficient in GSH synthesis and the other deficient in PC synthesis using selenite and arsenate as toxicants. The study revealed that selenium induces the synthesis of glutathione but rather use it as reductant and precursor for transformation and incorporation into peptides and neither GSH nor PCs play any role in selenium detoxification. It was also observed that when selenium and arsenic co-exist there could be competition for PCs between the ions of the metalloids with potentials for increasing arsenic toxicity. Human exposure to inorganic arsenic, a group 1 carcinogen, through Oryza sativa (rice), the staple food for about half the population of the world, has raised serious concerns. Most worrisome are the findings that rice grown in arsenic contaminated areas is characterised by reduced essential amino acids and micronutrients including selenium. A study was therefore conducted to to investigate and understand the interactions between selenium and arsenic in rice. The study confirmed that arsenic could limit the amount of selenium that is taken and translocated to the grains. Selenium was also found to reduce the toxicity of arsenic and most importantly, the study showed that at an appropriate selenium concentration, arsenic uptake and translocation can be reduced.

No description available.

Inorganic arsenic is a toxic element known to cause various diseases and cancers in humans. Arsenic contamination is widespread worldwide, particularly in South-East Asia where arsenic-contaminated groundwater is used for drinking and rice cultivation. Unlike other cereals, paddy rice can efficiently accumulate arsenic in the grain. Rice is a staple food for around 50% of the world's population, so arsenic accumulation in rice is of great concern. Arsenite, As(III), is the predominant form of arsenic within plants, but rice grains often contain significant proportions of organic arsenic species. The most common of these are dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA). A series of axenic experiments demonstrated that plants are unable to methylate arsenic, and instead take these species up from soil where they are produced by micro-organisms. The uptake of undissociated MMA by rice roots is predominantly facilitated by OsNIP2;1 (OsLsi1), a member of the NIP-subfamily of aquaporins, which also accounts for 50% of root DMA uptake. Expression of OsNIP1;1 and OsNIP3;3 in Xenopus oocytes demonstrated that these NIP aquaporins are permeable to pentavalent MMA, as well as arsenite, silicon and water. However, uptake of DMA was not observed for oocytes expressing any NIP gene, including OsNIP2;1. MMA and DMA have a pKa1 of 4.19 and 6.14 respectively, and so increasing the pH of the medium increases the proportion of dissociated complexes. In hydroponic culture, rice plants over-expressing the high-affinity phosphate transporter OsPT8, took up significantly more MMA and DMA than wild-type. Additionally, the presence of phosphate in the medium significantly decreased the uptake of both MMA and DMA by OsPT8-overexpression and wild-type rice plants. Therefore we have discovered that methylated arsenic species are not formed within plants, and can be transported by two different classes of transporters depending on the pH of the medium.

The new Maximum Contaminant Level (MCL) of arsenic in drinking water has caused a significant increase in the volume of arsenic-bearing solid residuals (ABSR) generated by drinking water utilities. Iron sorbents are being widely utilized for water treatment and comprise the bulk of the waste generated. Based on Toxicity Characteristic Leaching Procedure (TCLP) results, these ABSR may be disposed in municipal solid waste (MSW) landfills. However unlike the conditions in the TCLP, a mature landfill is a biotic, reducing environment where iron and arsenic may be reduced and, as a consequence, arsenic may be released to the leachate. The primary route of iron reduction in landfills is microbially mediated and biomineralization is a common by-product. In this case, biomineralization is the transformation of ferric (hydr)oxides into ferrous iron crystalline forms, such as siderite, vivianite and iron sulfide, and into mixed valent mineral forms, such as magnetite and green rust. In this work, biomineralization is evaluated as a possible process to control arsenic leaching from ABSR in landfills. Understanding biomineralization impacts, however, requires a precise knowledge of the various mechanisms of arsenic release under landfill conditions. To this end, we describe flow-through laboratory column experiments in which controlled conditions similar to those found in a mature landfill prevail. In these simulated landfill column experiments, the results show that biomineralization would naturally occur in typical non-hazardous MSW landfills. Without any intervention, As leaching was higher than 80% of the initial quantity loaded, in contrast to Fe leaching values, which were less than 10% of the initial quantity loaded. Phosphate and bicarbonate played an important role in the experiments, as probably arsenic competitors for sorption sites and as components of the secondary iron mineral phases, vivianite and siderite respectively. Although these minerals have less surface area and adsorption capacity than AFH, they were a key constituent on the retention of the As that was left in the columns by re-adsorbing As species, and more important by coating the AFH with some of the initially loaded As.

No description available.

No description available.

Elevated arsenic (As) concentrations in surface water from storing mine tailings in lakes can have a negative impact on local and downstream vegetation and aquatic life. At Terra Mine, an abandoned silver and copper mine in the Northwest Territories, tailings storage in Ho-Hum Lake has resulted in dissolved As concentrations of 50-80 μg/L, exceeding the 5 μg/L maximum guideline for aquatic life. A natural wetland located downstream appears to be attenuating As from surface water. The objectives of this study was to understand the sources of As to the wetland, the effectiveness of the wetland to sequester As, the form and stability of As in the sediments, the processes controlling As mobility, and the effect of seasonal changes in the wetland in the dissolved phase. Arsenic bound to the sediments was determined by analyzing for bulk composition, and As speciation and element association were identified using synchrotron-based bulk XANES and ESEM analysis. Arsenic enters the wetland by surface flow from Ho-Hum Lake, subsurface flow through the waste rock airstrip, and by windblown dust. In spring, dissolved As concentrations in surface water increased downstream. In late summer, a decrease in concentration was observed in the upstream portion of the wetland, however As returned to lake concentrations further downstream. Sediment As concentrations increased over the summer. ESEM and bulk XANES indicate that As was associated with (oxy)hydroxides and secondary sulphides. In the spring, when water levels were high from snow melt, (oxy)hydroxides formed and captured As, while sulphide oxidation in the sediments lead to the release of As into surface water. Over the summer, the onset of reducing conditions from microbial activity drove the formation of As-bearing sulphides and dissolution of (oxy)hydroxides. While As was accumulating in the sediments at most sites in the wetland over the summer, these results suggest that the wetland was not effectively sequestering dissolved As from the surface water, and that sediment-water cycling of As in the wetland as a result of seasonal redox variations were contributing As in the surface water. / Thesis (Master, Geological Sciences & Geological Engineering) -- Queen's University, 2011-06-24 12:46:26.649