No abstract available. / Thesis (M.Sc.Eng.)-University of Durban-Westville, 2000.

Arsenic (As) is a carcinogenic agent that is present in varying levels in environmental matrices including water and food. Long term As exposure can lead to skin lesions, peripheral neuropathy, diabetes, renal system effects and cardiovascular diseases. Bio-monitoring of human urine, toenail, serum and cerebrospinal fluid was carried out in this thesis to assess the exposure to arsenic and other trace elements. A multidisciplinary approach based on Inductively Coupled Plasma Mass Spectrometry (ICP-MS), HPLC-ICP-MS and Proton-Nuclear Magnetic Resonance Spectroscopy (1H-NMR) in conjunction with a questionnaire based survey was employed. The impact of rice consumption (a well-known vector of arsenic in the general population) on human urinary As levels was assessed. Results obtained show that the Bangladeshi (UK-B) community in the United Kingdom, who consume ca. 30-fold more rice than the white Caucasians (UK-C), are exposed to a higher level of arsenic. ICP-MS and HPLC-ICP-MS revealed a significant increase in dimethylarsinic acid (DMA) and inorganic arsenic (iAs) species in UK-B compared to UK-C, while cationic compounds were lower in UK-B than in UK-C. DMA and iAs levels in the Bangladeshis were positively correlated to rice consumption. Rice is likely to be responsible for the increase in levels of DMA and iAs in urine of UK-B. The link between this and the disproportional occurrence of diabetes and cardiovascular diseases (CVD) in UK-B needs to be investigated. Another important finding of this study is that the DMA to monomethyl arsenic (MA) ratio, which is often used as an indication of arsenic methylation capacity, should be applied with caution in populations consuming large quantities of rice because variation in the quantity and type of rice eaten may alter the urinary DMA levels and thereby the DMA/MA ratio. Urinary arsenic, selenium, copper and zinc were monitored for a group of Bangladeshis, Pakistanis, Indians and Caucasians living in the UK. The most striking finding was the increase in urinary copper in the UK-B group compared to other ethnicities and to reference values reported for the general UK population. Among the possible reasons for this could include dietary exposure via ethnic food consumption or a change in copper metabolism in the Bangladeshis. High serum copper levels have been correlated to CVD in the US population. In this context, further work is recommended to investigate if there is a relationship between urinary copper and the disproportionately high incidence of CVD in UK Bangladeshis. An approach based on 1H-NMR was used to detect changes in human urinary metabolomic profile as a function of As exposure through different routes. For this, the urine of UK-B, UK-C and a group residing in Bangladesh (BD-B) were monitored. The effects of other factors were explored, including arsenic urinary profile, chewing pan, ethnicity, rice consumption, selenium and diabetes. The three populations show distinctive metabolomic profiles. Urinary arsenic speciation was used in evaluating the effects of arsenic on the metabolomic profile for the UK group. This revealed that the %DMA positively correlates to %N,N-dymethylglycine, %alanine and %betaine. Comparative analysis of the 1H NMR spectra revealed that the BD-B urinary profiles were depleted in the number and quantity of metabolites. Visible signs of lower protein intake and undernourishment emerged from the urinary metabolomic profile of BD-B including a 2.5 decrease in creatinine levels compared to UK-B. Urinary creatinine and the metabolomic profile provide evidence for undernourishment in the BD-B population group that was not evident from previous studies on dietary protein intake in this population performed using food frequency questionnaires. Public health officials might consider also using bio-monitoring studies for nutrient intake rather than solely relying on estimations from food frequency questionnaires. The results reveal the complexity of the subject and pave the way for future studies, highlighting the need for awareness about diet and other specific confounding factors. Multiple Sclerosis (MS) is considered a multifactorial disease and its cause remains unknown. A case-control study on a MS cluster from the volcanic region of Mt. Etna (a natural emitter of geogenic trace elements in the environment) was undertaken. Urine and toenails were monitored for trace elements along with food consumption and life-style habits. Levels of a range of trace elements were reported for the first time for a population living in the Mt. Etna region. No significant differences were found in trace element levels in urine and toenails of MS patients and controls. However, urinary levels of nickel, manganese and selenium were higher than those reported in the literature for the general population from Italy, Germany and the UK. These findings and observations might suggest a role for nickel in the pathology of MS. However, larger studies on the possible role of nickel on MS, and trace elements in general, should be performed. Cerebrospinal fluid (CSF) and some serum from MS patients and controls from the Mt. Etna region were also monitored in this study using ICP-MS. There were significant differences in the trace elemental profile of CSF of MS volunteers and controls, including an increase in arsenic and zinc in the CSF of MS patients. Lead, aluminium, cadmium and molybdenum were significantly increased in the CSF of MS patients as well. In contrast, selenium was lower in MS patients compared to controls. The enrichment of certain trace elements in the CSF of MS patients could be the result of an impairment of the blood brain barrier and tight junction disruption due to MS and its progression, resulting in serum protein leakage and trace elements across the blood–brain barrier. Studies are necessary in the future to identify the chemical species present in the CSF and also determine their role in biological processes including their harmful effects on the brain.

Dissolution of arsenic bearing minerals in groundwater (used as drinking water) can lead to concentrations of >0.05 mg/L of arsenite in many countries, causing serious health effects. Several existing technologies rely on coagulation and adsorption to remove the less toxic form of arsenate (As (V)) (easier to remove from solution than As (III) due to its anionic charge) and the use of harsh oxidants (e.g. ozone). In this work nanocrystalline titanium dioxide (TiO₂) has been used as a photocatalytic oxidant (PCO) to oxidise As (III) which also functions as an adsorbent with a high surface area to remove the As (V) from solution. Most previous research has monitored only As (III) removal from solution and the mechanism of PCO is a controversial topic.  The main aim of this work was to use X-ray Photoelectron Spectroscopy (XPS) to study the adsorption and speciation of arsenic adsorbed on TiO₂ following PCO.  Aims also included finding a suitable commercial TiO₂, characterisation of adsorption of As (V), PCO reactions under different conditions, speciation of arsenic adsorbed by XPS and preliminary studies of the mechanism of PCO and the binding of arsenic species to the surface.

Rice consumption is responsible for the largest dietary contribution of inorganic arsenic. In addition to the direct human health impact of arsenic, arsenic toxicity impacts on rice yield. Thus two issues must be addressed: rice sensitivity to arsenic and the contribution of rice towards dietary arsenic. The grass Holcus lanatus achieves arsenate tolerance through the constitutive down regulation of phosphate transporters, which facilitate arsenate uptake. To gain a better understanding of mechanisms underlying arsenic sensitivity in rice and determine if phosphate uptake was responsible for differential arsenic sensitivity between two rice cultivars (Azucena and Bala) an experiment was undertaken examining the role of phosphate in rice arsenic sensitivity. Although high phosphate treatments were found to provide protection against both arsenate and arsenite toxicity and the two cultivars were found to respond differently to phosphate induced protection, the mechanism underlying reduced arsenic sensitivity did not appear to be controlled through a reduced phosphate uptake system. Attempts to link lab-based arsenic sensitivity of various rice cultivars to published biomass and tissue arsenic concentrations of rice grown in the field is presented. No consistent trend was identified across field sites although two negative correlations at two different sites were found (grain arsenic concentrations and shoot dry weight plotted against arsenate sensitivity). These data demonstrated the importance environment influence on traits examined. These correlations suggest that breeding for more arsenic resistant rice strains may increase plant yield but inadvertently lead to an increase in grain arsenic. Finally, QTL mapping and genome-wide association mapping were used to identify genomic regions and candidates genes responsible for variations in shoot arsenic concentrations in rice. The purpose of which was to offer a better understanding of the mechanisms responsible for this variation. Unfortunately the QTLs revealed were not reproduced in the association mapping study. A list of potential positional candidate genes are summarised and functional candidates identified and discussed.

Over the last decades, arsenic (As) contamination of soil-plant-water systems has become a major concern for Bangladesh and West Bengal, India. The geochemistry of the sediment depositional environment which subsequently, on sediment burial, give rise to elevated As in Holocene groundwater’s of Southeast Asia, may provide clues to unravelling the mechanistic basis and spatial heterogeneity of this phenomenon. The Sundarbans mangrove ecosystem, Bangladesh, is a modern analogue, and indeed forms a continuum with, the Holocene sediments of concern and thus studying As cycling in surface Sundarbans sediments. Similarly, rice paddy fields in many regions of the Bengal Basin form a continuum with Holocene sediments. Sediment cores were collected from a wide range of locations within the Sundarbans to study surface spatial, as well as down the profile (~1 m), As distribution and it’s association with other geochemical parameters. Pore and surface water, and Diffusive Gradients in Thin films (DGT) were sampled from 4 different interlocked sub-habitats over 0.29 km2: major river bank, main tributary, forest floor and minor tributary. Further experiments were conducted to observe As dynamics in mangrove surface sediments on application of mangrove detritus. Finally 3 interlinked experiments (field manuring, soil batch culture, greenhouse growth trials) were conducted to assess the effect of farm-yard manure (FYM) and rice straw, at a field application rate practised in Bangladesh (5 t/ha), on As mobilization in soil and subsequent assimilation by rice. As concentration in mangrove sediment down the profile was found to be more associated with elevated Fe and Mn than with organic matter (OM), with significant spatial variations among the locations. Sediment particle size was an important factor determining As retention and mobilization, which is also true for deeper Bengal Bay sediments. Proximity to mangrove vegetation and to water bodies was found to have significant effect on As dynamics. Porewaters from coarse textured, low OM riverbank sediment were high in As, but with only a small pool of As for resupply from the solid phase, showing similarities with grey aquifer sediments compared to fine textured and high OM content forest floor sediments. The As column dynamics study showed that As release into porewater was strongly associated with Fe release, indicating the strong association of the 2 elements, with OM playing a major role in their dissolution. The desorption studies also showed OM driving As mobilization within short time. Due to strong redox cycling very little evidence of As methylation was observed in biologically active mangrove porewaters. But we found 10-fold increase in dimethylarsinic acid (DMA) production compared to a non-amended control using the same sediments treated with mangrove detritus in the laboratory. OM amendments lead to considerable mobilization of As into both soil porewaters and standing surface waters in rice paddy. In a greenhouse rice cultivation experiment, flooding initially caused greatly enhanced As mobilization in porewater (< 24 d), but the effects of flooding on As mobilization decreased during later rice growth, particularly at grain fill. However, OM amendment did not cause significant As accumulation in grain and straw compared to control. It was noted in field trials and greenhouse studies that OM fertilization greatly enhanced As mobility to surface waters, which may have major implications for fate of As in paddy agronomic ecosystems.

Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA(III)), which accumulates in glial cells without compromising cell viability. MMA(III) LD50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA(III) concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA(III) concentrations that also induced TNF-α over-expression. Other effects of MMA(III) on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA(III) concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA(III) induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

Thesis advisor: Rudolph Hon / Groundwater in the Shepley's Hill Landfill (SHL) area had a high arsenic concentration for at least 20 years. This study is aimed at understanding the migration pathways of arsenic in the SHL area and postulating the possible sources and mechanisms for the mobilization of arsenic. A direct-push sampling technique (DPT) was applied in the summer of 2010 within the SHL and its downgradient area, which provided groundwater samples from various depths and locations. A long-term monitoring dataset from 1998 to 2009 was utilized as a subsidiary source for temporal analysis. Spatial distributions of arsenic and other major dissolved compositions were analyzed. Extremely high arsenic concentrations (up to ~ 15000 µg/L) were detected in the deep glacial sand deposits close to a peat layer within the SHL. Arsenic concentrations decrease dramatically in the downgradient area north of the SHL. The transport of arsenic in the SHL area is similar to that of iron. The source of arsenic is likely to been within the boundary of the SHL. The glacial sand overburden within the SHL provides enough source for the arsenic mobilization. A possible mechanism of arsenic mobilization in the SHL area is that the reductive dissolution/desorption of arsenic from iron bearing minerals under a lasting reducing environment created by decompositions of organic matter in waste and peat. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Earth and Environmental Sciences.

Thesis advisor: Rudolph Hon / In the northeast United States, arsenic (As) contamination in groundwater is frequently associated with historical landfill leachate plumes. Based on the history of Shepley's Hill Landfill (SHL) in Devens, MA, solid waste disposal activities spanned nearly a century of landfilling with little or no documentation of when or what waste material was disposed. Past geochemical investigations proved the presence of high levels of As in groundwaters within and around the SHL region. A total of 114 samples were collected from the SHL region and analyzed for their hydrogeochemistry and isotopic signature. Since the isotopic ratios of äD and ä18O can potentially be influenced by the mobilization process of As, this study attempts to identify any correlations between the stable isotopic ratios and the hydrogeochemistry of SHL waters. The results of the groundwater hydrogeochemical analysis show multiple relationships between metal concentrations and As concentration levels, typical of groundwater undergoing redox reactions. The result of the stable isotope analysis show significant fractionation of stable isotope ratios away from the meteoric water line. However, the role of strong redox gradients and various redox ladder reactions involving water did not produce a significant correlation with the isotopic fractionations present within different zones of the landfill. In most cases, the fractionations stand independent of the increase/decrease in As concentration and can be attributed to either unrelated chemical reactions within groundwater or evaporation. / Thesis (MS) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Earth and Environmental Sciences.

Lam Kin Bong Hubert. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 139-161). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / (in chinese) --- p.iv / Acknowledgements --- p.vi / Publications --- p.ix / Table of Contents --- p.x / List of Tables --- p.xiii / List of Figures --- p.xiv / List of Abbreviations --- p.xvi / Chapter CHAPTER1： --- General Introduction --- p.1 / Chapter Section 1.1 --- Historical Background and Application of Arsenic Trioxide as an Anti-cancer Agent --- p.1 / Chapter Section 1.2 --- Arsenic Trioxide Induces Apoptosis in Cancer Cells --- p.3 / Chapter 1.2.1 --- The Intrinsic and Extrinsic Pathways of Apoptosis Initiation --- p.4 / Chapter 1.2.2 --- The Convergence of Pathways --- p.8 / Chapter 1.2.3 --- Induction of Apoptosis by Arsenic Trioxide --- p.9 / Chapter 1.2.3.1 --- Controversies in the Involvement of the Extrinsic Pathway --- p.9 / Chapter 1.2.3.2 --- "Arsenic Trioxide, Oxidative Stress and the Mitochondria" --- p.10 / Chapter 1.2.3.3 --- Caspase-3 Activation in Arsenic Trioxide-mediated Apoptosis --- p.12 / Chapter Section 1.3 --- Arsenic Trioxide Perturbs the Cell Division Cycle --- p.13 / Chapter 1.3.1 --- The Cell Cycle Oscillator --- p.14 / Chapter 1.3.2 --- DNADamage and Cell Cycle Checkpoints --- p.15 / Chapter 1.3.3 --- Induction of Cell Cycle Arrest by Arsenic Trioxide and its Association with Apoptosis --- p.17 / Chapter Section 1.4 --- Acute Megakaryocytic Leukemia and Arsenic Trioxide --- p.20 / Chapter CHAPTER 2： --- Objectives --- p.28 / Chapter CHAPTER 3： --- Methodology --- p.30 / Chapter Section 3.1 --- Materials --- p.30 / Chapter Section 3.2 --- Methods --- p.39 / Chapter 3.2.1 --- Culture of Megakaryocytic Cells and Their Treatment with Arsenic Trioxide --- p.39 / Chapter 3.2.1.1 --- Maintenance of Cell Lines --- p.39 / Chapter 3.2.1.2 --- Treatment with Arsenic Trioxide --- p.39 / Chapter 3.2.2 --- "Effects of Arsenic Trioxide on Cell Proliferation, Apoptosis, Mitochondrial Integrity and Cell Division Cycle Profiles of Human Megakaryocytic Leukemia Cell Lines" --- p.40 / Chapter 3.2.2.1 --- Trypan Blue Exclusion Assay --- p.40 / Chapter 3.2.2.2 --- Quantitation of Externalized Phosphatidylserine --- p.41 / Chapter 3.2.2.3 --- Quantitation of Active Caspase-3 Expression --- p.42 / Chapter 3.2.2.4 --- Assessment of Mitochondrial Intensity --- p.42 / Chapter 3.2.2.5 --- Analysis of Cell Division Cycle Profile --- p.43 / Chapter 3.2.2.6 --- Analysis of Cell Cycle Kinetics by BrdU Labeling --- p.43 / Chapter 3.2.2.7 --- Identification of Cell Cycle Specificity of Caspase-3 Expression --- p.45 / Chapter 3.2.3 --- Effects of Arsenic Trioxide on the Expression of Apoptotic Signals in Human Megakaryocytic Leukemia Cell Lines --- p.45 / Chapter 3.2.3.1 --- Effects of Arsenic Trioxide on mRNA Expression Levels of Apoptotic Regulators --- p.45 / Chapter 3.2.3.2 --- Effects of Arsenic Trioxide on Protein Expression Levels of Apoptotic Regulators --- p.50 / Chapter 3.2.3.2.1 --- Flow Cytometric Analysis --- p.50 / Chapter 3.2.3.2.2 --- Western Blot Analysis --- p.51 / Chapter 3.2.4 --- Effects of Arsenic Trioxide on Gene Expression Profiles of Human Megakaryocytic Leukemia Cell Lines By Microarray Analysis --- p.54 / Chapter 3.2.5 --- Statistical Analysis --- p.57 / Chapter CHAPTER 4： --- "Effects of Arsenic Trioxide on Cell Proliferation, Apoptosis, Mitochondrial Integrity and Cell Division Cycle Profiles of Human Megakaryocytic Leukemia Cell Lines" --- p.62 / Chapter Section 4.1 --- Introduction --- p.62 / Chapter Section 4.2 --- Results --- p.63 / Chapter 4.2.1 --- Effects of Arsenic Trioxide on Proliferation Kinetics --- p.63 / Chapter 4.2.2 --- Effects of Arsenic Trioxide on Cell Viability --- p.64 / Chapter 4.2.3 --- Apoptosis-inducing Capability of Arsenic Trioxide --- p.65 / Chapter 4.2.3.1 --- Quantitation of Externalized Phosphatidylserine --- p.65 / Chapter 4.2.3.2 --- Quantitation of Active Caspase-3 Expression --- p.66 / Chapter 4.2.4 --- Effects of Arsenic Trioxide on Mitochondrial Integrity --- p.67 / Chapter 4.2.5 --- Effects of Arsenic Trioxide on Cell Division Cycle Profiles --- p.69 / Chapter 4.2.6 --- Effects of Arsenic Trioxide on Cell Cycle Kinetics by Bromodeoxyuridine Labeling --- p.69 / Chapter 4.2.7 --- Identification of Cell Cycle Specificity of Arsenic Trioxide-Induced Caspase-3 Activation --- p.71 / Chapter Section 4.3 --- Discussion --- p.72 / Chapter CHAPTER 5： --- Effects of Arsenic Trioxide on Apoptotic Signal Expression in Human Megakaryocytic Leukemia Cell Lines --- p.91 / Chapter Section 5.1 --- Introduction --- p.91 / Chapter Section 5.2 --- Results --- p.92 / Chapter 5.2.1 --- Effects of Arsenic Trioxide on mRNA Expression Levels of Apoptotic Regulators --- p.92 / Chapter 5.2.2 --- Effects of Arsenic Trioxide on Protein Expression Levels of Apoptotic Regulators --- p.94 / Chapter 5.2.2.1 --- Flow Cytometric Analysis --- p.94 / Chapter 5.2.2.2 --- Western Blot Analysis --- p.96 / Chapter Section 5.3 --- Discussion --- p.96 / Chapter CHAPTER 6： --- Effects of Arsenic Trioxide on Gene Expression Profiles of Human Megakaryocytic Leukemia Cell Lines by Microarray Analysis --- p.119 / Chapter Section 6.1 --- Introduction --- p.119 / Chapter Section 6.2 --- Results --- p.119 / Chapter Section 6.3 --- Discussion --- p.122 / Chapter CHAPTER 7： --- General Discussion and Conclusions --- p.135 / BIblography --- p.139

Chronic exposure to naturally occurring arsenic (As) in groundwater threatens the health of >150 million villagers in S/SE Asia. In Bangladesh, low As aquifers offer the best hope of reducing the exposure of 35-40 million remain exposed to elevated levels of As in drinking water (>10 μg/L). These low As aquifers could be affected, however, by massive pumping from shallow (<30 m) depths for growing rice and overexploitation of deeper aquifer for municipal water supply. The goal of this dissertation is to assess the impacts of groundwater pumping on the distribution in groundwater of dissolved As, reactive carbon, and redox-sensitive elements in anoxic aquifers of Bangladesh based on long-term hydrologic measurements, geochemical analyses, and numerical flow modeling. In the second chapter, changes in the well-water As concentrations within a 25 sq. km area over a 10+ year timespan are assessed on the basis of continuous time series for 18 monitoring wells, a set of 271 wells resampled three times, and a large dataset obtained from blanket surveys of several thousand wells in the region. The two larger data sets both show a 10% decline in the initial areal mean As of 100 μg/L. This decline can be explained by flushing of As in the shallow aquifer by low-As recharge water, evidently compensated to some extent by the desorption of sediment-bound As. The presence of a large exchangeable pool of As in the sediment therefore seems to buffer changes in the distribution of As in the face of large perturbation in groundwater flow, albeit not enough to prevent some trends indicated by the detailed time series. The third chapter provides a complementary perspective on groundwater-sediment interactions by quantifying the rates of adsorption and desorption of As with column experiments conducted in the field for two different types of sediments: grey reduced Holocene sands and orange oxidized Pleistocene sands. The data show that, contrary to widely held beliefs, retardation of As transport by adsorption is quite similar in Holocene and Pleistocene sediments, even if Holocene sands initially contain a much larger pool of easily mobilizable As. The field column experiments also showed significant changes in solid phase speciation that affected As retention within a timespan of only a few weeks. Detailed field observations and flow modeling in the fourth chapter examine how perturbed flow paths can draw either As or reactive carbon into a Pleistocene aquifer. A groundwater flow model, constrained by head measurements and isotopic tracer data shows that certain portions of the aquifer are becoming increasingly contaminated with As as a result of municipal pumping, but against a background of redox transformation in the aquifer that probably preceded this perturbation. Overall, the research conducted for this thesis shows that alteration of the hydrological system due to local and regional forcing is affecting the distribution of As in groundwater. These changes do not affect all wells yet and, if they do, the increase in As concentrations observed so far are gradual because of the buffering capacity of the sediment. Lowering exposure by targeting low As aquifer should therefore definitely continue in Bangladesh, with particular attention paid to regular monitoring using vulnerability criteria this research has helped to identify.