Organic Forms Of Arsenic Research Articles

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM.Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM.We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58–3.77) and MMA% (aOR = 1.95 (95% CI 0.81–4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25–1.52), though the confidence intervals included the null value.While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

Arsenobetaine in Seawater: Depth Profiles from Selected Sites in the North Atlantic.

Arsenic occurs in marine waters, typically at concentrations of 1-2 μg As kg-1, primarily as the inorganic species arsenate. Marine animals, however, contain extremely high levels of arsenic (typically 2000-20 000 μg As kg-1 wet mass), most of which is present as arsenobetaine, an organic form of arsenic that has never been found in seawater. We report a method based on ion-exchange preconcentration and HPLC/mass spectrometry to measure arsenobetaine in seawater, and apply the method to samples of seawater collected at various depths from seven sites in the North Atlantic. Arsenobetaine was detected in most samples at levels ranging from 0.5 to 10 ng As kg-1, and was found at depths down to 4900 m. Furthermore, we report the presence of 15 additional organoarsenicals in seawater, 14 of which had never been detected in marine waters. The arsenobetaine depth profile was related, albeit weakly, to that of chlorophyll; this relationship probably reflects arsenobetaine's release to water from marine animals associated with the euphotic zone rather than its direct biosynthesis by primary producers. Future application of the new method for seawater analysis will shed new light on the biogeochemical cycle of marine arsenic.

A Comparative Assessment of Arsenic Risks and the Nutritional Benefits of Fish Consumption in Kuwait: Arsenic Versus Omega 3-Fatty Acids.

Inorganic and organic forms of arsenic (As), as well as omega-3 fatty acids were measured in 578 fish/seafood samples that belong to15 species of commonly consumed seafood in Kuwait. Arsenic speciation data, with the toxicological profile of inorganic arsenic (iAs) and fish consumption rates were applied in a probabilistic risk assessment to estimate the risk from exposure to iAs. The nutritional benefits of omega-3-fatty acid levels in various species of fish were taken into consideration. Results showed that the mean daily intake of iAs through fish consumption among the Kuwaiti population was 0.058µg/kg/day, and the 95th percentile was 0.15µg/kg/day. Although the mean intake level did not exceed the incremental lifetime cancer risk (ILCR) at 1×10-4, the 95th percentile of iAs intake showed an ILCR of 2.7×10-4. Kuwaiti children (aged 6-12years) were found to have a higher mean intake of iAs at 0.10µg/kg/day with 68% of children in this category, exceeding the risk specific dose associated with an ILCR of 1×10-4. The fish species, hammor (grouper; Epinephelus coioides), is the top contributor to iAs intake, and tuna is the major source of omega 3-fatty acids for the Kuwaiti population.

Development and validation of a simple and robust method for arsenic speciation in human urine using HPLC/ICP-MS.

In order to better distinguish the different toxic inorganic and organic forms of arsenic (As) exposure in individuals, we have developed and validated a simple and robust analytical method for determining the following six As species in human urine: arsenous (III) acid (As-III), As (V) acid, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine (AsB), and arsenocholine. In this method, human urine is diluted using a pH 5.8 buffer, separation is performed using an anion exchange column with isocratic HPLC, and detection is achieved using inductively coupled plasma-MS. The method uses a single mobile phase consisting of low concentrations of both phosphate buffer (5 mM) and ammonium nitrate salt (5 mM) at pH 9.0; this minimizes the column equilibration time and overcomes challenges with separation between AsB and As-III. In addition, As-III oxidation is prevented by degassing the sample preparation buffer at pH 5.8, degassing the mobile phase online at pH 9.0, and by the use of low temperature (-70 °C) and flip-cap airtight tubes for long term storage of samples. The method was validated using externally provided reference samples. Results were in agreement with target values at varying concentrations and successfully passed external performance test criteria. Internal QC samples were prepared and repeatedly analyzed to assess the method's long-term precision, and further analyses were completed on anonymous donor urine to assess the quality of the method's baseline separation. Results from analyses of external reference samples agreed with target values at varying concentrations, and results from precision studies yielded absolute CV values of 3-14% and recovery from 82 to 115% for the six As species. Analysis of anonymous donor urine confirmed the well-resolved baseline separation capabilities of the method for real participant samples.

Arsenic speciation in soils and Erica andevalensis Cabezudo & Rivera and Erica australis L. from São Domingos Mine area, Portugal

Arsenic is very abundant in the Iberian Pyrite Belt (IPB) and it might have hazardous consequences for plants. The chemical speciation is an important factor to take into account in toxicity evaluations. Arsenate is analogous to phosphate and it can seriously interfere with cellular processes. In the present study we have analysed by high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) the arsenic speciation in soils from São Domingos mine area (IPB) and arsenate resulted to be the major species. The arsenic content and speciation analysis have been carried out also in two metal tolerant species from that area: Erica andevalensis, endemic heather from the mining areas of the Southwest Iberian Peninsula, and Erica australis, a widely distributed species. The total content of arsenic ranged in soils from 194 to 7924mgkg−1 (dry mass), and from 1 to 24.4mgkg−1 in E. andevalensis and from 2.7 to 11.6mgkg−1 in E. australis. The organic forms of arsenic were almost absent, with only dimethylarsinate (DMA) found in some samples of E. andevalensis. These plant species must possess different tolerance mechanisms, as E. australis accumulates mainly arsenite, while in E. andevalensis arsenate is the most abundant species in some cases.

Speciation of arsenic metabolites in the free-living mouse Mus spretus from Doñana National Park used as a bio-indicator for environmental pollution monitoring

AbstractA speciation approach based on orthogonal chromatographic systems coupled to inductively coupled plasma mass spectrometry (ICP-MS) was used to characterise the biological response of free-living mice Mus spretus to environmental pollution caused by arsenic in different areas of the Doñana National Park (south-west Spain). The relative presence of inorganic and organic forms of arsenic was studied in cytosolic extracts from high metabolic activity organs of Mus spretus mice: kidneys, liver, and brain. An instrumental coupling of size-exclusion chromatography with UV and collision/reaction cell-ICP-MS detectors (SEC-UV-ICP-ORC-MS) both in analytical and preparative scale was used for this purpose. The results showed the presence of low molecular mass (LMM) molecules linked to arsenic in these tissues especially in the kidneys, where the presence of these arsenic metabolites was higher. On the other hand, the presence of these arsenicals varied from one area to the other, which can be related to a different occurrence of contaminants. These low molecular mass fractions were collected by preparative SEC chromatography for later study with ion exchange chromatography and detection by ICP-ORC-MS, using both anionic and cationic columns. The results showed the higher presence of MMA and DMA in kidneys of mice caught in contaminated areas and the existence of small amounts of unidentified arsenicals when cation-exchange chromatography was used, which could be related to the presence of dimethylarsinoylethanol (DMAE), thioarsenic species, or arsenocholine (AsC).

Contribution of organic arsenic species to total arsenic measurements using ferrihydrite-backed diffusive gradients in thin films (DGT)

Environmental contextBoth the mobility and toxicity of arsenic in natural waters are related to the aqueous species distribution. Passive sampling using ferrihydrite-backed diffusive gradients in thin films (DGT) devices has in previous studies been characterised to measure labile inorganic arsenic, and the possible contribution of organic species has been disregarded. This study shows that the two most prevalent organic arsenic species might be included in DGT measurements, which should be taken into consideration when evaluating DGT data in future studies. AbstractIn previous publications discussing arsenic determination using ferrihydrite-backed diffusive gradients in thin films (DGT) devices, organic arsenic forms have been disregarded, even though it is known that the two most prevalent in natural waters, dimethylarsinate (DMA) and monomethylarsonate (MMA), may adsorb to ferrihydrite and thereby be included in the measurement. In this work the accumulation of DMA and MMA, as well as inorganic arsenite and arsenate, to ferrihydrite-backed DGT devices was investigated. It could be demonstrated that MMA, and under acidic conditions also DMA, adsorbed to the binding layer and might therefore contribute to the total mass of measured arsenic. Diffusion coefficients were measured for all four species to enable quantification of DGT-labile concentrations of organic and inorganic arsenic. Elution of the analytes from the ferrihydrite binding layer was performed using 1 mL of 1 M NaOH to facilitate arsenic speciation analysis using chromatographic separation. Average recovery rates were between 87 and 108 %. This study shows that the contribution of DMA and MMA to the total accumulated mass must be taken into consideration when evaluating DGT data in future studies.

Targeting EVI1-Overexpressing AML with Darinaparsin

Abstract 4269Ecotropic viral integration site 1 (EVI1) is a critical oncogene driving a subset of myeloid malignancies and overexpression of EVI1 predicts an extremely poor prognosis in both adult and pediatric AML patient populations. Activation of EVI1, due to chromosomal translocation, inversion or transcriptional upregulation, occurs in 8–10% of AML and results in both activation and repression of specific gene sets. Importantly, the tumor suppressor PTEN is repressed by EVI1. Arsenic trioxide targets EVI1 for degradation, suggesting that arsenicals may be effective in treating EVI1-positive malignancies. Indeed, MDS patients with EVI1 deregulation had greater benefit from the combination of arsenic trioxide (inorganic arsenic) and thalidomide than patients without EVI1 deregulation. Here, we describe the use of a novel arsenical, darinaparsin (an organic form of arsenic), to treat a patient with EVI1-overexpressing AML, as a 10th line of chemotherapy.A 36 year old woman was diagnosed with AML inv(3)(q21q26.2) where two copies of inv(3) were detected. Her initial treatment included two induction regimens followed by an allogeneic stem cell transplant. She had complete remission lasting 5 years after which time her AML relapsed. Three high dose regimens, including VP16 (4g) and cyclophosphamide (2.7g), failed to induce another remission (>80% blasts in the bone marrow). She was offered an investigational combination therapy of ribavirin and low dose cytarabine but after one month, her peripheral blast count rose to >60 and was not responding to hydrea (8g) or mitoxantrone (20mg). At this time, we compared the anti-tumor activity of arsenic trioxide and darinaparsin on the patient's peripheral blasts in vitro and found that darinaparsin induced significantly more cell death than arsenic trioxide. Thus, the patient started darinaparsin (300 mg/m2 IV over 60 minutes for 5 days every 21 days). Within 10 hours of receiving her first dose, her fever and night sweats had resolved. She regained her energy and appetite and was discharged home 2 days after her last dose. Unlike previous drug regimens, darinaparsin allowed the patient to enjoy a good quality of life for more than 30 days with an ECOG performance status of 1. Unfortunately, while darinaparsin stabilized her peripheral white blood cell counts, the patient died of extramedullary manifestations and complications of her AML, 36 days after receiving the first dose of darinaparsin.Darinaparsin decreased her peripheral white blood cell counts during the five days of treatment, which was followed by an additional decrease in the white blood cell count when serum arsenic levels were low to undetectable. We observed visible nuclear and cytoplasmic blebbing consistent with cells undergoing apoptosis. Although EVI1 protein levels were difficult to measure consistently, we analyzed the transcriptional repression activity of EVI1 by measuring PTEN mRNA expression. Intriguingly, we found a significant increase in PTEN mRNA in leukemic blasts following each course of darinaparsin, supporting the hypothesis that darinaparsin may target EVI1 or its activity. We utilized cDNA microarray expression profiling and found that gene expression of her tumor changed dramatically between the first and second cycle, including a significant increase in the pro-survival NF-κB pathway. NF-κB family member (i.e. NFKB1, 2, IA, IB, IE, RELA, TANK, TRAF1 and TRAF2) mRNA expression increased 2–8 fold following the first cycle of darinaparsin. Based on these data, we conclude that darinaparsin should be further explored as a treatment for EVI1-overexpressing myeloid malignancies using the transcriptional repression activity of EVI1 by measuring PTEN mRNA expression as a biomarker for identification of patients likely to respond to therapy. Disclosures:Mann:ZIOPHARM Oncology Inc: Research Funding. Morgan:ZIOPHARM Oncology Inc: Employment. Miller:ZIOPHARM Oncology Inc: Research Funding.

Microbial Arsenic Metabolism: New Twists on an Old Poison

Imagine a planet with an atmosphere lacking oxygen, its landscape dotted with volcanic craters, caustic oceans, and basins of brine. Yet, amazingly, these oceans and brines teem with life, albeit very different from our own—microorganisms that breathe arsenic. That description may describe the Earth during the early Archean eon. Although breathing arsenic may sound alien, microorganisms that use arsenic oxyanions for anaerobic respiration are found in environmental niches ranging from garden soil and subsurface aquifers to more extreme landscapes such as Mono Lake and Searles Lake in California. Diverse microorganisms metabolize both inorganic and organic forms of arsenic, and their activities are part of a robust biogeochemical cycle. What began more than 15 years ago as our quest to learn how bacteria use arsenate as a terminal electron acceptor led us to discover novel respiratory and photosynthetic pathways.

Speciation of Arsenic from Soil Organic Matter in Abandoned Gold and Silver Mines, Korea

Organic forms of arsenic (As) were determined through fractionation procedure of soil organic matter (SOM) in soil, sediments and mine tailing samples from the Myungbong, Dongil, and Okdong mining areas of southern Korea. An alkaline extraction method was applied to soil samples followed by the fractionation procedures of SOM by the DAX-8 and XAD-4 resin adsorption method. Major fraction of organic As species (42% to 98%) was found in acid-soluble fraction, whereas minor fraction (0.1 % to 67.8%) was present in the humic-associated As. In acid-soluble fractions, the transphillic- and hydrophilic-associated As were dominant in addition to As binding with humic and fulvic SOM. Arsenic binding was the strongest between pH 6 to 8 and reduced to about 70% at both low and high pH regions. The amount of both transphillic and hydrophillic associated As was less changed than humic and fulvic-associated As, in both low and high pH regions. This apparently indicates that As has stronger affinity towards hydrophillic rather than hydrophobic organics. From the experimental observation of As-binding SOM in natural soil, the ligand exchange model may be a feasible explanation of transphillic and hydrophillic affinity of As.

Effect of biosolid incorporation on arsenic distribution in Mollisol soils in central Chile

The effect of biosolid incorporation on arsenic distribution in Mollisol soils in central Chile was studied. Two soils were sequentially extracted for arsenic with a five-step method that accounts for the following arsenic forms: non-specifically adsorbed (F1), specifically adsorbed (F2), amorphous and poorly crystallized Fe and Al oxides (F3), well-crystallized Fe and Al oxides (F4) and residual (F5). The arsenic residual fraction was predominant in Pintué soil, whereas in Graneros soil, arsenic was mostly associated to amorphous Fe and Al oxides. Graneros soil exhibited a higher As(V) adsorbing capacity than Pintué soil, which relates to the higher clay and iron and aluminum oxides contents, confirming that these components participation is essential for the adsorption of this metalloid. Biosolid application at a rate of 100 Mg ha −1 caused an increase in arsenic bound to amorphous Fe and Al oxides and in the residual fraction, in Pintué soil. When Pintué soil was spiked with arsenic, aged for two months, and treated with biosolid (100 Mg ha −1), the content of arsenic in the most labile fractions decreased, thus showing a favorable effect in its application to soils with few specific sites for arsenic adsorption. Arsenic speciation was carried out in the first two fractions of the sequential extraction procedure. As(V) was the main form in both fractions. Biosolid incorporation at a rate of 100 Mg ha −1 caused a significant increase in organic arsenic forms.

Arsenic Speciation in Lichens and in Coarse and Fine Airborne Particulate Matter by HPLC–UV–HG–AFS

A three-step sequential extraction procedure with Milli-Q, CaCl2 and H3PO4 was applied for extraction of arsenic species in lichen transplants and airborne particulate matter (fine and coarse fractions). The samples used in this work were collected in 1994–1995 near coal-fired power plants. Both transplant lichens and airborne particulate matter were submitted to the same environment simultaneously. Arsenic species identification and quantification was performed by HPLC–UV–HG–AFS. Inorganic forms of arsenic (arsenite and arsenate) were present in significant amounts in most of the samples. Only in lichens also organic forms of arsenic (monomethyl arsonic acid and dimethyl arsinic acid) were identified which may indicate biotransformation of inorganic arsenic.

Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA)

Research in our laboratory has demonstrated that a trivalent form of arsenic such as arsenic trioxide (AT) has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells (HepG2). However, the literature also indicates that the toxicity of arsenic depends on its chemical form. To test this hypothesis, we further evaluated the cellular and molecular responses of HepG2 cells following exposure to monosodium acid methanearsonate (MSMA), a pentavalent and organic form of arsenic. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the gene profile assay was performed to measure the degree of gene induction in 13 different recombinant cell lines generated from a parental HepG2 cell line. Cytotoxicity experiments yielded LC50 values of 11.9 + 2.6 μg/mL for AT, and 257.3 + 51.4μg/mL for MSMA; indicating that AT was about 20 times more toxic than MSMA. Exposure of HepG2 cells to MSMA also resulted in a significant reduction (p < 0.05) in the number of stress genes induced, compared to AT. Upon MSMA exposure, only 2 (HMTIIA and HSP70) out of the 13 constructs evaluated yielded inductions to statistically significant levels (p < 0.05), compared to 11 (GSTYa, XRE, HMTIIA, c-fos, NF-kBRE, HSP70, p53RE, GADD153, GADD45, and GRP78) for AT. These results greatly support the hypothesis that the toxicity of arsenic compounds highly depends on their chemical forms; with the inorganic forms being more potent than the organic ones.

Arsenic speciation: limitations with direct hydride analysis

Speciation of inorganic arsenic(III) by hydride evolution directly into an atomic-absorption system was found to be subject to error when organic forms of arsenic (such as dimethylarsinic acid) were present. Organic forms of arsenic can produce an underestimation of total arsenic when the hydride response from concentrated acid is quantitated against inorganic arsenic. Hydride responses from solutions of various acidities are reported for dimethylarsinic acid, monomethylarsonic acid, inorganic arsenic(III) and inorganic arsenic(V). Even simultaneous equations did not provide a means of resolving mixtures of the four arsenic species investigated by using direct analysis of the evolved hydrides.

Arsenic metabolism in a marine food chain

Radioarsenic was used to identify various chemical forms of arsenic, accumulated as arsenate from food or water, in a three-step food chain consisting of an autotroph, a grazer and a carnivore. Differential extraction procedures carried out on tissues from these organisms suggest that organic forms of arsenic in marine food webs are derived from an in vivo synthesis by primary producers and are efficiently transferred along a marine food chain. The muscle tissue of the carnivorous shrimp which represented the highest trophic level in this food chain could not itself form organic arsenic; in this case arsenate taken up from water was converted largely to arsenite.