Monday, December 31, 2012

Sign the petition to stop genocide through gold mining and arsenic release in Paracatu.

Anthropogenic arsenic is piling up worldwide because of disastrous projects such as Canadian Kinross Gold Corporation's gold mining in Paracatu, Brazil. Kinross obtains financial and political support from the Canadian government. Kinross obtains permits for its activities of genocidal stature by corruption, facilitation payments, black mailing and even murder. The people of Paracatu and a number of institutions like Acangau Foundation in Brazil and the Halifax Initiative in Canada are desperately seeking sanction for Kinnross’ genocidal activities. We urge the Canadian Government to stop financing Kinross, start indemnizing the Paracatu people. We urge the governments of Brazil and Canada to impose a complete ban on gold mining in arsenic-bearing deposits. 

Why this is important: 

To obtain tens of tonnes of gold, Canadian Kinross Gold Corporation has released more than 300 hundred thousand tonnes of inorganic arsenic from the rocks of its open cut gold mine in Paracatu, a 90 thousand inhabitant town in Brazil. In the next 30 years, Kinross will release 1 million tonnes of this dreadful environmental toxicant into the biosphere. One gram of inorganic arsenic is enough to instantly kill seven adult people or cause chronic disease like cancer, diabetes, cardiovascular diseases and Alzheimer's disease if the exposure occurs over years or decades. Accordingly, the incidences of cancer, abortion and other diseases have increased significantly in Paracatu since Kinross initiated its gold mining activities in town. There is no such thing as a safe dose for a cancer causing substance like arsenic. The arsenic released by Kinross into the air, soil and water in Paracatu is bioaccessible to millions of living beings including people in Brazil and worldwide. The incredible amounts of arsenic from Paracatu will persist in the environment for hundreds to thousands of years causing persistent, chronic killings, human suffering and poverty. 

For additional information, please refer to:

Thursday, December 13, 2012

Arsenic uptake and metabolism in plants.

New Phytol. 2009 Mar;181(4):777-94. 
Zhao FJ, Ma JF, Meharg AA, McGrath SP. 
Soil Science Department, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ, UK. 
Abstract - Arsenic (As) is an element that is nonessential for and toxic to plants. Arsenic contamination in the environment occurs in many regions, and, depending on environmental factors, its accumulation in food crops may pose a health risk to humans.Recent progress in understanding the mechanisms of As uptake and metabolism in plants is reviewed here. Arsenate is taken up by phosphate transporters. A number of the aquaporin nodulin26-like intrinsic proteins (NIPs) are able to transport arsenite,the predominant form of As in reducing environments. In rice (Oryza sativa), arsenite uptake shares the highly efficient silicon (Si) pathway of entry to root cells and efflux towards the xylem. In root cells arsenate is rapidly reduced to arsenite, which is effluxed to the external medium, complexed by thiol peptides or translocated to shoots. One type of arsenate reductase has been identified, but its in planta functions remain to be investigated. Some fern species in the Pteridaceae family are able to hyperaccumulate As in above-ground tissues. Hyperaccumulation appears to involve enhanced arsenate uptake, decreased arsenite-thiol complexation and arsenite efflux to the external medium, greatly enhanced xylem translocation of arsenite, and vacuolar sequestration of arsenite in fronds. Current knowledge gaps and future research directions are also identified.

Growth of a bacterium that apparently uses arsenic instead of phosphorus is a consequence of massive ribosome breakdown.

J Biol Chem. 2012 Aug 17;287(34):28816-9. 
Basturea GN, Harris TK, Deutscher MP. 
Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. 
Abstract - A recent study (Wolfe-Simon, F., Switzer Blum, J., Kulp, T. R., Gordon, G. W., Hoeft, S. E., Pett-Ridge, J., Stolz, J. F., Webb, S. M., Weber, P. K., Davies, P. C., Anbar, A. D., and Oremland, R. S. (2011) Science 332, 1163-1166) described the isolation of a special bacterial strain, GFAJ-1, that could grow in medium containing arsenate, but lacking phosphate, and that supposedly could substitute arsenic for phosphorus in its biological macromolecules. Here, we provide an alternative explanation for these observations and show that they can be reproduced in a laboratory strain of Escherichia coli. We find that arsenate induces massive ribosome degradation, which provides a source of phosphate. A small number of arsenate-tolerant cells arise during the long lag period prior to initiation of growth in +As/-P medium, and it is this population that undergoes the very slow, limited growth observed for both E. coli and GFAJ-1. These results provide a simple explanation for the reported growth of GFAJ-1 in arsenate without invoking replacement of phosphorus by arsenic in biological macromolecules.

Urinary arsenic levels in the French adult population: the French National Nutrition and Health Study, 2006-2007.

Sci Total Environ. 2012 Sep 1;433:206-15. 
Saoudi A, Zeghnoun A, Bidondo ML, Garnier R, Cirimele V, Persoons R, Fréry N. 
Institut de Veille Sanitaire, Département Santé Environnement, Saint-Maurice, France. 
Abstract - The French Nutrition and Health Survey (ENNS) was conducted to describe dietary intakes, nutritional status, physical activity, and levels of various biomarkers for environmental chemicals (heavy metals and pesticides) in the French population (adults aged 18-74 years and children aged 3-17 years living in continental France in 2006-2007). The aim of this paper was to describe the distributions of total arsenic and the sum of iAs+MMA+DMA in the general adult population, and to present their main risk factors. In the arsenic study, 1500 and 1515 adults (requested to avoid seafood intake in the previous 3 days preceding urine collection) were included respectively for the analysis of the sum of inorganic arsenic (iAs) and its two metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and for the total arsenic. Results were presented as geometric means and selected percentiles of urinary arsenic concentrations (μg/L) and creatinine-adjusted urinary arsenic (μg/g of creatinine) for total arsenic, and the sum of inorganic arsenic and metabolites (iAs+MMA+DMA). The geometric mean concentration of the sum of iAs+MMA+DMA in the adult population living in France was 3.34 μg/g of creatinine [3.23-3.45] (3.75 μg/L [3.61-3.90]) with a 95th percentile of 8.9 μg/g of creatinine (10.68 μg/L). The geometric mean concentration of total arsenic was 11.96 μg/g of creatinine [11.41-12.53] (13.42 μg/L [12.77-14.09]) with a 95th percentile of 61.29 μg/g of creatinine (72.75 μg/L). Urinary concentrations of total arsenic and iAS+MMA+DMA were influenced by sociodemographic and economic factors, and by risk factors such as consumption of seafood products and of wine. In our study, covariate-adjusted geometric means demonstrated several slight differences, due to consumption of fish, shellfish/crustaceans or wine. This study provides the first reference value forarsenic in a representative sample of the French population not particularly exposed to high levels of arsenic (10 μg/g of creatinine). It shows that urinary arsenic concentrations in the French adult population (in particular concentrations of iAs+MMA+DMA) were relatively low compared with foreign data.

Thioarsenate formation upon dissolution of orpiment and arsenopyrite.

Chemosphere. 2012 Nov;89(11):1390-8. 
Suess E, Planer-Friedrich B. 
University of Bayreuth, Environmental Geochemistry, Universitaetsstrasse 30, 95440 Bayreuth, Germany. 
Abstract - Thioarsenates were previously determined as dominant species in geothermal and mineral waters with excess sulfide. Here, we used batch leaching experiments to determine their formation upon weathering or industrial leaching of the arsenic-sulfide minerals orpiment (As(2)S(3)) and arsenopyrite (FeAsS) under different pH and oxygen conditions. Under acidic conditions, as expected based on their known kinetic instability at low pH, no thioarsenates formed in either of the two mineral systems. Under neutral to alkaline conditions, orpiment dissolution yielded mono-, di- and trithioarsenate which accounted for up to 43-55% of total arsenic. Thioarsenate formation upon arsenopyrite dissolution was low at neutral (4%) but significant at alkaline pH, especially under suboxic to sulfidic conditions (20-43%, mainly as monothioarsenate). In contrast to orpiment, we postulate that recombination of arsenite and sulfide in solution is of minor importance for monothioarsenate formation during alkaline arsenopyrite dissolution. We propose instead that hydroxyl physisorption lead to formation of As-OH-S surface complexes by transposition of hydroxyl anions to arsenic or iron sites. Concurrently formed ironhydroxides could provide re-sorption sites for the freshly released monothioarsenate. However, sorption experiments with goethite showed slower sorption kinetics of monothioarsenate compared to arsenite, but comparable with arsenate. The discovery that thioarsenates are released by natural weathering and industrial leaching processes and that, once they are released, have a higher mobility than the commonly-investigated species arsenite and arsenate requires future studies to consider them when assessing arsenic release in sulfidic natural or mining-impacted environments.

Exposure of soil microbial communities to chromium and arsenic alters their diversity and structure.

PLoS One. 2012;7(6):e40059. 
Sheik CS, Mitchell TW, Rizvi FZ, Rehman Y, Faisal M, Hasnain S, McInerney MJ, Krumholz LR.
Department of Botany and Microbiology, University of Oklahoma, Norman, Oklahoma, United States of America. 
Abstract - Extensive use of chromium (Cr) and arsenic (As) based preservatives from the leather tanning industry in Pakistan has had a deleterious effect on the soils surrounding production facilities. Bacteria have been shown to be an active component in the geochemical cycling of both Cr and As, but it is unknown how these compounds affect microbial community composition or the prevalence and form of metal resistance. Therefore, we sought to understand the effects that long-term exposure to As and Cr had on the diversity and structure of soil microbial communities. Soils from three spatially isolated tanning facilities in the Punjab province of Pakistan were analyzed. The structure, diversity and abundance of microbial 16S rRNA genes were highly influenced by the concentration and presence of hexavalent chromium (Cr (VI)) and arsenic. When compared to control soils, contaminated soils were dominated by Proteobacteria while Actinobacteria and Acidobacteria (which are generally abundant in pristine soils) were minor components of the bacterial community. Shifts in community composition were significant and revealed that Cr (VI)-containing soils were more similar to each other than to As contaminated soils lacking Cr (VI). Diversity of the arsenic resistance genes, arsB and ACR3 were also determined. Results showed that ACR3 becomes less diverse as arsenic concentrations increase with a single OTU dominating at the highest concentration. Chronic exposure to either Cr or As not only alters the composition of the soil bacterial community in general, but affects the arsenic resistant individuals in different ways.

The role of irrigation techniques in arsenic bioaccumulation in rice (Oryza sativa L.).

Environ Sci Technol. 2012 Aug 7;46(15):8333-40. 
Spanu A, Daga L, Orlandoni AM, Sanna G. 
Dipartimento Agraria, Università di Sassari, Via De Nicola 1, I-07100 Sassari, Italy. 
Abstract - The bioaccumulation of arsenic compounds in rice is of great concern worldwide because rice is the staple food for billions of people and arsenic is one of the most toxic and carcinogenic elements at even trace amounts. The uptake of arsenic compounds in rice comes mainly from its interaction with system soil/water in the reducing conditions typical of paddy fields and is influenced by the irrigation used. We demonstrate that the use of sprinkler irrigation produces rice kernels with a concentration of total arsenic about fifty times lower when compared to rice grown under continuous flooding irrigation. The average total amount of arsenic, measured by a fully validated ICP-MS method, in 37 rice grain genotypes grown with sprinkler irrigation was 2.8 ± 2.5 μg kg(-1), whereas the average amount measured in the same genotypes grown under identical conditions, but using continuous flooding irrigation was 163 ± 23 μg kg(-1). In addition, we find that the average concentration of total arsenic in rice grains cultivated under sprinkler irrigation is close to the total arsenic concentration found in irrigation waters. Our results suggest that, in our experimental conditions, the natural bioaccumulation of this element in rice grains may be completely circumvented by adopting an appropriate irrigation technique.

Effect of environmental exposure of arsenic on cattle and poultry in Nadia district, West Bengal, India.

Toxicol Int. 2012 Jan;19(1):59-62. 
Datta BK, Bhar MK, Patra PH, Majumdar D, Dey RR, Sarkar S, Mandal TK, Chakraborty AK. 
Department of Pharmacology and Toxicology, West Bengal University of Animal and Fishery Sciences, 37, K.B. Sarani, Kolkata, India. 
Abstract - A study was undertaken to evaluate an alternative source of arsenicosis in human food chain through livestock. Thirty milch cattle and 20 poultry birds along with their eggs were selected randomly from two endemic villages of Nadia district and one nonendemic villages of Hooghly district in West Bengal, India. Milk, feces, urine, and hair samples of cattle and feed materials, such as water and straw, were collected to analyze arsenic status.Arsenic concentration in egg yolk and albumen from poultry eggs and different poultry organs after culling was estimated. Distribution of arsenic in animal body indicates that major portion of arsenic was eliminated through feces, urine, and milk. Poultry egg yolk, albumen, and poultry products retain arsenic in all organs. Cows and poultry birds reared in endemic zone retain significantly higher concentration of arsenic. Consumption of egg, agricultural produces grown in contaminated soil, and milk might have produced arsenicosis and may be considered as alternative source of arsenic contamination.

Arsenic and lead contamination in urban soils of Villa de la Paz (Mexico) affected by historical mine wastes and its effect on children's health studied by micronucleated exfoliated cells assay.

Environ Geochem Health. 2012 Jun 27. [Epub ahead of print]
Gamiño-Gutiérrez SP, González-Pérez CI, Gonsebatt ME, Monroy-Fernández MG. 
Programa Multidisciplinario de Posgrado en Ciencias Ambientales, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico. 
Abstract - Environmental geochemical and health studies were carried out in urban areas of Villa de la Paz, S.L.P. (Mexico), where mining activities have been developed for more of 200 years, leading to the pollution of surface soil by arsenic and heavy metals (Pb, Cd, Cu, Zn). The analysis of urban soils to determine total and bioaccessibility concentrations of As and Pb, demonstrated a combined contribution of the natural and anthropogenic concentrations in the site, at levels higher than the environmental guideline values that provoke a human health risk. Contour soil mapping confirmed that historical mine waste deposits without environmental control measures, are the main source of pollution soil by As and Pb in the site. Exposure (Pb in blood and As in urine) and effect (micronucleated exfoliated cells assay) biological monitoring were then carried out in the childhood population of the site and in a control site. The exposure biological monitoring demonstrated that at least 20-30 % of children presented Pb and As exposure values higher than the national and international maximum intervention values. The effect biomonitoring by MEC assay confirmed that there is a genotoxic damage in local childhood population that could be associated with the arsenic exposure in the site.

Fluvial transport and surface enrichment of arsenic in semi-arid mining regions: examples from the Mojave Desert, California.

J Environ Monit. 2012 Jul;14(7):1798-813. 
Kim CS, Stack DH, Rytuba JJ. 
School of Earth and Environmental Sciences, Schmid College of Science and Technology, Chapman University, Orange, CA 92866, USA. 
Abstract - As a result of extensive gold and silver mining in the Mojave Desert, southern California, mine wastes and tailings containing highly elevated arsenic(As) concentrations remain exposed at a number of former mining sites. Decades of weathering and erosion have contributed to the mobilization of As-enriched tailings, which now contaminate surrounding communities. Fluvial transport plays an intermittent yet important and relatively undocumented role in the migration and dispersal of As-contaminated mine wastes in semi-arid climates. Assessing the contribution of fluvial systems to tailings mobilization is critical in order to assess the distribution and long-term exposure potential of tailings in a mining-impacted environment. Extensive sampling, chemical analysis, and geospatial mapping of dry streambed (wash) sediments, tailings piles, alluvial fans, and rainwater runoff at multiple mine sites have aided the development of a conceptual model to explain the fluvial migration of mine wastes in semi-arid climates. Intense and episodic precipitation events mobilize mine wastes downstream and downslope as a series of discrete pulses, causing dispersion both down and lateral to washes with exponential decay behavior as distance from the source increases. Accordingly a quantitative model of arsenic concentrations in wash sediments, represented as a series of overlapping exponential power-law decay curves, results in the acceptable reproducibility of observed arsenic concentration patterns. Such a model can be transferable to other abandoned mine lands as a predictive tool for monitoring the fate and transport of arsenic and related contaminants in similar settings. Effective remediation of contaminated mine wastes in a semi-arid environment requires addressing concurrent changes in the amounts of potential tailings released through fluvial processes and the transport capacity of a wash.

The palaeosol model of arsenic pollution of groundwater tested along a 32 km traverse across West Bengal, India.

Sci Total Environ. 2012 Aug 1;431:157-65. 
Hoque MA, McArthur JM, Sikdar PK. 
Earth Sciences, University College London, Gower Street, London WC1E 6BT, UK. 
Abstract - The distribution of As-pollution in groundwater of the deltaic aquifers of south-eastern Asia may be controlled by the subsurface distribution of palaeo-channel sediments (As-polluted groundwaters) and palaeo-interfluvial sediments (As-free groundwaters). To test this idea, termed the palaeosol model of As-pollution, we drilled 10 sites, analysed groundwater from 249 shallow wells (screened < 107 mbgl), field-tested another 149 for As, and used colour as a guide to the presence or absence of As-pollution in a further 531 wells. Our work was conducted along a 32-km traverse running W to E across southern West Bengal, India. At seven drill sites we logged a palaeo-interfluvial sequence, which occurs as three distinct units that together occupy 20 km of the traverse. These palaeo-interfluvial sequences yield As-free groundwaters from brown sands at depth < 100 m. The palaeo-interfluvial sequences are separated by two deep palaeo-channels, which were logged at 3 sites. The palaeo-channel deposits host As-polluted groundwater in grey sands. Our findings confirm the predictions of the palaeosol model of As-pollution. We show again that well-colour can be used both to successfully predict the degree of As-pollution in groundwater, and to locate regions of buried palaeo-interfluve that will yield As-free groundwater for the foreseeable future.

A Guillain-Barré Syndrome-like neuropathy associated with arsenic exposure.

J Occup Health. 2012 May 29. [Epub ahead of print] 
Kim S, Takeuchi A, Kawasumi Y, Endo Y, Lee H, Kim Y. 
Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine. 
Abstract - Objectives: We report on a patient presenting with an isolated polyneuropathy mimicking Guillain-Barré syndrome (GBS) associated with arsenicexposure. Case: A 43-year-old man visited our emergency room complaining of progressive quadriparesis over the prior 5 days. His clinical course with laboratory data was typical of GBS. However, because of his recent use of herbal medication, we screened for the presence of several heavy metals. Serial analyses of inorganic arsenic concentrations confirmed exposure to arsenic. He was diagnosed as arsenic neuropathy mimicking GBS without any systemic manifestation of arsenic intoxication. Conclusions: The present case study emphasizes the need to consider arsenicintoxication in patients presenting with acute demyelinating neuropathies and histories of herbal medication use.

Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway.

Arch Toxicol. 2012 Jun;86(6):923-33. 
Yen YP, Tsai KS, Chen YW, Huang CF, Yang RS, Liu SH. 
College of Medicine, Institute of Toxicology, National Taiwan University, Taipei, Taiwan. 
Abstract - A pool of myoblasts available for myogenesis is important for skeletal muscle size. The decreased number of skeletal muscle fibers could be due to the decreased myoblast proliferation or cytotoxicity. Identification of toxicants that regulate myoblast apoptosis is important in skeletal muscle development or regeneration. Here, we investigate the cytotoxic effect and its possible mechanisms of arsenic trioxide (As(2)O(3)) on myoblasts. C2C12 myoblasts underwent apoptosis in response to As(2)O(3) (1-10 μM), accompanied by increased Bax/Bcl-2 ratio, decreased mitochondria membrane potential, increased cytochrome c release, increased caspase-3/-9 activity, and increased poly (ADP-ribose) polymerase (PARP) cleavage. Moreover, As(2)O(3) triggered the endoplasmic reticulum (ER) stress indentified through several key molecules of the unfolded protein response, including glucose-regulated protein (GRP)-78, GRP-94, PERK, eIF2α, ATF6, and caspase-12. Pretreatment with antioxidant N-acetylcysteine (NAC, 0.5 mM) dramatically suppressed the increases in reactive oxygen species (ROS), lipid peroxidation, ER stress, caspase cascade activity, and apoptosis in As(2)O(3) (10 μM)-treated myoblasts. Furthermore, As(2)O(3) (10 μM) effectively decreased the phosphorylation of Akt, which could be reversed by NAC. Over-expression of constitutive activation of Akt (c.a. Akt) also significantly attenuated As(2)O(3)-induced myoblast apoptosis. Taken together, these results suggest that As(2)O(3) may exert its cytotoxicity on myoblasts by inducing apoptosis through a ROS-induced mitochondrial dysfunction, ER stress, and Akt inactivation signaling pathway.

Antiapoptotic efficacy of folic acid and vitamin B₁₂ against arsenic-induced toxicity.

Environ Toxicol. 2012 May;27(6):351-63. 
Majumdar S, Maiti A, Karmakar S, Das AS, Mukherjee S, Das D, Mitra C. 
Institute of Genetic Medicine and Genomic Science, Madhyamgram, Kolkata, India. 
Abstract - Earlier, we proposed that the ability of folic acid and vitamin B₁₂ to preserve systemic and mitochondrial function after short-term exposure to arsenicmay prevent further progression to more permanent injury and pathological changes leading to cell death. To elucidate its mechanism, the present study examined the antiapoptotic efficacy of folic acid and vitamin B₁₂ against short-term arsenic exposure-induced hepatic mitochondria oxidative stress and dysfunction. Sixteen to eighteen weeks old male albino rats weighing 140-150 × g were divided into five groups: Control (A), Arsenic-treated (B), Arsenic + folic acid (C), Arsenic +vitamin B₁₂ (D), and Arsenic + folic acid + vitamin B₁₂ (E). Data generated indicated that folic acid and vitamin B₁₂ separately or in combination can give significant protection against alterations in oxidative stress and apoptotic marker parameters and downstream changes in mitochondria, namely pro-oxidative (NO, TBARS, OH⁻) and antioxidative defense (SOD, CAT, GSH) markers, iNOS protein expression, mitochondrial swelling, cytochrome c oxidase and Ca²⁺-ATPase activity, Ca²⁺ content, caspase-3 activity. Additionally, results of hepatic cell DNA fragmentation, arsenic load of blood, hepatic tissue and urine, and histological observations, all strongly support that both these supplements have efficacy in preventing apoptotic changes and cellular damage. As the mechanisms of actions of both of these supplements are methylation related, a combined application was more effective. Results further reveal new molecular targets through which folic acid and vitamin B₁₂ separately or in combination work to alleviate one critical component of arsenic-induced liver injury: mitochondria dysfunction.

Relationship of creatinine and nutrition with arsenic metabolism.

Environ Health Perspect. 2012 April; 120(4): a145–a146. 
Mary V. Gamble 
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York. 
Basu et al. (2011) reported the associations of both dietary and blood nutrient measures, as well as urinary creatinine (uCr), with arsenic (As) methylation capacity, as assessed by the proportions of urinary inorganic, monomethyl, and dimethyl As metabolites. One finding was that uCr was the strongest predictor of As methylation; participants with higher uCr concentrations had a higher percentage of total urinary As as dimethylarsinic acid (DMA) compared to those with lower uCr. This is consistent with what we have previously reported in Bangladeshi adults and children (Gamble et al. 2005; Ahsan et al. 2007; Hall et al. 2009), and is an interesting and potentially very important observation. Approximately 40% of S-adenosylmethionine (SAM)-derived methyl groups are devoted to the biosynthesis of creatine, the precursor of creatinine (Brosnan et al. 2011; Mudd and Poole 1975). At high levels of As exposure (500–1,000 µg/L), based on one-carbon kinetics (Schalinske and Steele 1989), we estimated that methylation of 80% of a daily dose of inorganic As (InAs) to DMA would require approximately 50 µmol SAM, thus consuming approximately 2–4% of the SAM normally turning over in a well-nourished adult per day. Low dietary creatine intake associated with low-protein or vegetarian diets places an increased demand for SAM for creatine biosynthesis (Brosnan 2011). This could potentially reduce the availability of SAM for As methylation, providing a plausible mechanism underlying this highly reproducible observation. This assumes that uCr reflects, to some extent, dietary creatine intake, as we have observed (Gamble M, unpublished data). Conversely, dietary creatine intake and/or creatine supplementation down-regulates endogenous creatine biosynthesis, potentially sparing SAM for methylation of other substrates such as As. We are currently testing this hypothesis in a randomized controlled trial of creatine supplementation. In addition, as Basu et al. (2011) noted, and as we have previously reported (Gamble and Liu 2005), one implication of the observed association between uCr and As methylation capacity is that urinary As should not be expressed per gram creatinine to correct for urine concentration. Rather, uCr should be included as a covariate in regression models. One concerning aspect of the study by Basu et al. (2011) is the handling of blood samples used for nutrient measurements. As noted by Basu et al. and in a previous publication on these same participants (Chung et al. 2006), the blood samples were stored in an ice chest in the field for up to 24 hr before processing. This 24-hr delay can be problematic for some nutrients, especially folate, which is extremely sensitive to oxidative degradation (Drammeh et al. 2008). Basu et al. (2011) reported that in univariate analyses, they observed higher urinary percentages of InAs in individuals with higher serum folate concentrations. This finding is contrary to our previous findings that folate facilitates As methylation (Gamble et al. 2005, 2006, 2007; Hall et al. 2007, 2009). This discrepancy might be explained by differences in sample processing. Basu et al. (2011) also reported associations between dietary intake of several nutrients (assessed using a modified 24-hr recall) and As methylation capacity. One of the most critical and widely discussed issues in nutritional epidemiology is the method used to adjust for total energy intake (TEI) (Willett et al. 1997). The main reasons to adjust for TEI are to a) adjust for potential confounding by TEI, b) remove extraneous variation in nutrient intakes that is due only to their correlation with TEI, and c) simulate a dietary intervention. What is often most relevant is diet composition, or nutrient intake in relation to TEI (Willett et al. 1997). Several methods are available to adjust for TEI, and the best approach can vary depending on the nutrient and question of interest. Basu et al. (2011) adjusted for TEI by dividing each nutrient intake by TEI (nutrient density method). While this approach is appealing because of its simplicity, in reality it can create a complex variable (Willett and Stampfer 1998). For example, when TEI is related to the outcome of interest, the use of nutrient densities can actually induce confounding in the opposite direction. Although we cannot determine from Basu et al.’s article whether TEI measured by the 24-hr recall was associated with As methylation, in theory, an association seems plausible. Also, because their statistical analysis tested for associations between multiple nutrients and urinary As metabolites, it is best to acknowledge that some of the statistically significant associations might be due to chance alone. Go to: Footnotes The authors declare that they have no actual or potential competing financial interests. 

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Arsenic trioxide affects bone remodeling by effects on osteoblast differentiation and function.

Bone. 2012 Jun;50(6):1406-15. 
Hu YC, Cheng HL, Hsieh BS, Huang LW, Huang TC, Chang KL. 
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 
Abstract - Arsenic trioxide (ATO) is widely used in tumor treatment, but excessive arsenic exposure can have adverse health effects. This study was to examine the association between ATO treatment and bone remodeling. The effects of ATO on osteoblast function were investigated in primary cell cultures and in an in vivo study in rats. Sprague-Dawley rats (n=30) were randomly assigned to 3 groups which were injected intraperitoneally with saline or 5 or 10 mg/kg of ATO for 4 weeks. In cell culture, ATO decreased osteoblast mineralization by decreasing alkaline phosphatase (ALP) expression and this effect was prevented by co-addition of inorganic phosphate (Pi). Moreover, levels of mRNAs for the transcription factors runt-related transcription factor 2 (Runx2) and osterix, the osteoblast osteogenic gene osteocalcin, and the adherence molecule vascular cell adhesion molecule-1 (VCAM-1) were decreased by ATO. Levels of mRNAs for the cytokine IL-6 were also decreased, whereas GM-CSF mRNA levels were increased. Similar effects of ATO on osteoblasts were seen in in vivo experiments in the rat. Moreover, decreases of bone turnover markers of osteocalcin, Procollagen type I N-terminal propeptide (PINP), and C-terminal cross-linked telopeptide (CTX) as well as bone mineral density (BMD) and trabecular bone volume of femur were observed in ATO-treated rats. These results suggest that ATO interferes with bone remodeling mostly through changes in osteoblast differentiation and function.

Mitochondrial myopathy caused by arsenic trioxide therapy.

Blood. 2012 May 3;119(18):4272-4. 
Echaniz-Laguna A, Benoilid A, Vinzio S, Fornecker LM, Lannes B, Goullé JP, Broly F, Mousson de Camaret B. 
Département de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre,1 Avenue Molière, Strasbourg Cedex, France. 
Abstract - Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO therapy may provoke a delayed, severe, and partially reversible mitochondrial myopathy, and a long-term careful surveillance for muscle disease should be instituted when ATO is used in patients with APL.

Glutathione synthetase promotes the reduction of arsenate via arsenolysis of glutathione.

Biochimie. 2012 Jun;94(6):1327-33. 
Németi B, Anderson ME, Gregus Z. 
Department of Pharmacology and Pharmacotherapy, Toxicology Section, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary. 
Abstract - The environmentally prevalent arsenate (As(V)) undergoes reduction in the body to the much more toxic arsenite (As(III)). Phosphorolytic enzymes and ATP synthase can promote the reduction As(V) by converting it into arsenylated products in which the pentavalent arsenic is more reducible by glutathione (GSH) to As(III) than in inorganic As(V). Glutathione synthetase (GS) can catalyze the arsenolysis of GSH (γ-Glu-Cys-Gly) yielding two arsenylated products, i.e. γ-Glu-Cys-arsenate and ADP-arsenate. Thus, GS may also promote the reduction of As(V) by GSH. This hypothesis was tested with human recombinant GS, a Mg(2+) dependent enzyme. GS markedly increased As(III) formation when incubated with As(V), GSH, Mg(2+) and ADP, but not when GSH, Mg(2+) or ADP were separately omitted. Phosphate, a substrate competitive with As(V) in the arsenolysis of GSH, as well as the products of GSH arsenolysis or their analogs, e.g. glycine and γ-Glu-aminobutyrate, decreased As(V) reduction. Replacement of ADP with ATP or an analog that cannot be phosphorylated or arsenylated abolished As(V) reduction, indicating that GS-supported As(V) reduction requires formation of ADP-arsenate. In the presence of ADP, however, ATP (but not its metabolically inert analog) tripled As(V) reduction because ATP permits GS to remove the arsenolysis inhibitory glycine and γ-Glu-Cys by converting them into GSH. GS failed to promote As(V) reduction when GSH was replaced with ophthalmic acid, a GSH analog substrate of GS containing no SH group (although ophthalmic acid did undergo GS-catalyzed arsenolysis), indicating that the SH group of GSH is important for As(V) reduction. Our findings support the conclusion that GS promotes reduction of As(V) by catalyzing the arsenolysis of GSH, thus producing ADP-arsenate, which upon being released from the enzyme is readily reduced by GSH to As(III).

Influence of glutathione chemical effectors in the response of maize to arsenic exposure.

J Plant Physiol. 2012 May 1;169(7):649-56. 
Requejo R, Tena M. 
Department of Biochemistry and Molecular Biology, ETSIAM, University of Córdoba, Campus de Rabanales, Edificio Severo Ochoa, Ctra. N-IVa-Km 396, 14071 Córdoba, Spain. 
Abstract - To support the key role of glutathione (GSH) in the mechanisms of tolerance and accumulation of arsenic in plants, this work examines the impact of several effectors of GSH synthesis or action in the response of maize (Zea mays L.) to arsenic. Maize was exposed in hydroponics to iso-toxic rates of 150 μM arsenate or 75 μM arsenite for 9 days and GSH effectors, flurazole (an herbicide safener), l-buthionine-sulfoximine (BSO, a known inhibitor of GSH biosynthesis), and dimercaptosuccinate (DMS) and dimercaptopropanesulfonate (DMPS) (two thiols able to displace GSH from arsenite-GSH complexes) were assayed. The main responses of plants to arsenic exposure consisted of a biomass reduction (fresh weight basis) of about 50%, an increase of non-protein thiol (NPTs) levels (especially in the GSH precursor γ-glutamylcysteine and the phytochelatins PC₂ and PC₃) in roots, with little effect in shoots, and an accumulation of between 600 and 1000 ppm of As (dry weight basis) in roots with very little translocation to shoots. Growth inhibition caused by arsenic was partially or completely reversed in plants co-treated with flurazole and arsenate or arsenite, respectively, highly exacerbated in plants co-treated with BSO, and not modified in plants co-treated with DMS or DMPS. These responses correlated well with an increase of both NPTs levels in roots and glutathione transferase activity in roots and shoots due to flurazole treatment, the decrease of NPTs levels in roots caused by BSO and the lack of effect on NPT levels caused by both DMS and DMPS. Regarding to arsenic accumulation in roots, it was not modified by flurazole, highly reduced by BSO, and increased between 2.5- and 4.0-fold by DMS and DMPS. Therefore, tolerance and accumulation ofarsenic by maize could be manipulated pharmacologically by chemical effectors of GSH. 

Extremely High Urine Arsenic Level After Remote Seafood Ingestion.

Am J Ther. 2012 Mar 8. [Epub ahead of print] 
Nañagas KA, Tormoehlen LM. 
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Poison Center, Indianapolis, Indiana; and Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana. 
Abstract - Urine testing for heavy metal concentrations is increasingly performed in the outpatient setting as a part of laboratory evaluation for neuropathy. Abnormal urine arsenic levels due to dietary intake of organic arsenic can lead to unnecessary chelation therapy. A 54-year-old man underwent a 24-hour urine collection for heavy metal concentrations in evaluation of paresthesia of the right foot. The total arsenic level was 8880 μg/d with concentrations of 4749 μg/L and 3769 μg/g creatinine. He was urgently referred to the toxicology clinic for consideration of chelation therapy. History revealed consumption of 2 lobster tails 5 days before the testing. Speciation was then performed on the original urine specimen and revealed an organic arsenic concentration of 4332 μg/L. No inorganic or methylated arsenic was detected. Repeat testing after abstaining from seafood demonstrated a total arsenic level of 50 μg/d with concentrations of 30 μg/L and 21 μg/g creatinine. Our patient demonstrates the highest level of arsenobetaine reported in the literature, and this level is higher than expected for a person who had not consumed seafood for 5 days before testing. The high levels may be due to consumption of food that he did not recognize as containing arsenobetaine or that his clearance of arsenobetaine from the ingested lobster is slower than published ranges. This case demonstrates the importance of speciation when measuring urine arsenic levels to avoid unnecessary chelation therapy.

Speciated arsenic in air: measurement methodology and risk assessment considerations.

J Air Waste Manag Assoc. 2012 Jan;62(1):2-17. 
Lewis AS, Reid KR, Pollock MC, Campleman SL. 
Gradient, Cambridge, Massachusetts, USA. 
Abstract - Accurate measurement of arsenic (As) in air is critical to providing a more robust understanding of arsenic exposures and associated human health risks. Although there is extensive information available on total arsenic in air, less is known on the relative contribution of each arsenic species. To address this data gap, the authors conducted an in-depth review of available information on speciated arsenic in air. The evaluation included the type of species measured and the relative abundance, as well as an analysis of the limitations of current analytical methods. Despite inherent differences in the procedures, most techniques effectively separated arsenic species in the air samples. Common analytical techniques such as inductively coupled plasma mass spectrometry (ICP-MS) and/or hydride generation (HG)- or quartz furnace (GF)-atomic absorption spectrometry (AAS) were used for arsenic measurement in the extracts, and provided some of the most sensitive detection limits. The current analysis demonstrated that, despite limited comparability among studies due to differences in seasonal factors, study duration, sample collection methods, and analytical methods, research conducted to date is adequate to show that arsenic in air is mainly in the inorganic form. Reported average concentrations of As(III) and As(V) ranged up to 7.4 and 10.4 ng/m3, respectively, with As(V) being more prevalent than As(III) in most studies. Concentrations of the organic methylated arsenic compounds are negligible (in the pg/m3 range). However because of the variability in study methods and measurement methodology, the authors were unable to determine the variation in arsenic composition as a function of source or particulate matter (PM) fraction. In this work, the authors include the implications of arsenic speciation in air on potential exposure and risks. The authors conclude that it is important to synchronize sample collection, preparation, and analytical techniques in order to generate data more useful for arsenic inhalation risk assessment, and a more robust documentation of quality assurance/quality control (QA/QC) protocols is necessary to ensure accuracy, precision, representativeness, and comparability.

Could hydrolysis of arsenic substituted DNA be prevented? Protection arises from stacking interactions.

Chem Commun (Camb). 2012 Apr 14;48(30):3626-8. 
Wang J, Gu J, Leszczynski J. 
Interdisciplinary Nanotoxicity Center, Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217, USA. 
Abstract - Investigation of the hydrolysis of dinucleoside-arsenate-deoxyguanylyl-3',5'-deoxyguanosine (dGAsdG(-)) reveals that base-stacking in DNA increases the resistance of As-DNA towards hydrolysis. Base-stacking raises the activation energy of hydrolysis. Hydrolysis of As-DNA is found to be endothermic. The hydrolysis stability of As-DNA should be higher than that estimated based on arsenate diester models.

Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

PLoS Genet. 2012 Feb;8(2):e1002522. 
Pierce BL, Kibriya MG, Tong L, Jasmine F, Argos M, Roy S, Paul-Brutus R, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Quasem I, Hore SK, Alam S,Islam T, Slavkovich V, Gamble MV, Yunus M, Rahman M, Baron JA, Graziano JH, Ahsan H. 
Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America. 
Abstract - Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS) of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P < 5×10(-8)) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of individuals with prospectively measured arsenic (n = 769), we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01). Expression quantitative trait locus (eQTL) analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12)) and neighboring gene C10orf32 (P = 10(-44)), which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical skin lesion risk. The observed patterns of associations suggest that MMA% and DMA% have distinct genetic determinants and support the hypothesis that DMA is the less toxic of these two methylated arsenic species. These results have potential translational implications for the prevention and treatment of arsenic-associated toxicities worldwide.

Korea National Survey for Environmental Pollutants in the Human Body 2008: heavy metals in the blood or urine of the Korean population.

Int J Hyg Environ Health. 2012 Jul;215(4):449-57. 
Lee JW, Lee CK, Moon CS, Choi IJ, Lee KJ, Yi SM, Jang BK, Yoon BJ, Kim DS, Peak D, Sul D, Oh E, Im H, Kang HS, Kim J, Lee JT, Kim K, Park KL, Ahn R, Park SH, Kim SC, Park CH, Lee JH. 
Department of Environmental Health Sciences, College of Natural Science, Soonchunhyang University, Asan, South Korea. 
BACKGROUND: Recently, there have been several nationwide episodes involving imported toys contaminated with toxic metals and environmental hormones. In addition, cadmium intoxication has occurred due to soil contamination with cadmium from abandoned metal mines. OBJECTIVES: To investigate the distribution, extent and factors influencing the levels of toxic metals in the blood or urine of the Korean general population over twenty years of age, we studied the blood or urine concentrations of heavy metals in a representative sample of 5087 Koreans in 2008. METHODS: Multiple biological substrates were collected from each participant to determine the most suitable samples for an environmental health survey system. Information regarding exposure conditions of all subjects was collected by questionnaire-based interviews. RESULTS: The geometric means of the blood lead, mercury and manganese levels were 19.1, 3.23 and 10.8 μg/L, respectively. The geometric means of urinary arsenic and cadmium concentrations were 43.5 and 0.65 μg/L, respectively. Blood mercury and urinary arsenic levels in the Korean general population were significantly higher than in European and American populations. CONCLUSIONS: The higher levels of blood mercury and urinary arsenic could be explained by the greater seafood consumption among the Korean population. This biomonitoring study of blood or urine heavy metals in the Korean general population provides important reference data stratified by demographic and lifestyle factors that will be useful for the ongoing surveillance of environmental exposure of Koreans to toxic metals.

Arsenic encapsulation using Portland cement with ferrous sulfate/lime and Terra-Bond™ technologies - Microcharacterization and leaching studies.

Sci Total Environ. 2012 Mar 15;420:300-12.
Randall PM. 
U.S. Environmental Protection Agency, National Risk Management Research Laboratory, Land Remediation and Pollution Control Division, 26 W. Martin Luther King Drive, Cincinnati, OH 45268, USA. 
Abstract - This work reports the results of an investigation on the treatment and encapsulation of arsenic-containing materials by Portland cement with ferrous sulfate and lime (PFL) and Terra-Bond™, a commercially available patented technology. The arsenic materials included: chromated copper arsenate (CCA)-treated wood materials; scorodite-rich mine tailings from the La Trinidad Mine in California; and a soil/smelter dust mixture from the Anaconda Superfund site spiked with monosodium methyl arsenate (MSMA) to simulate an organoarsenic soil material. SEM/EDS and XRD spectra of PFL treated samples showed similarity across all three waste materials while Terra-Bond treated samples showed predominance of elemental sulfur. SEM/EDS of PFL treated samples showed that calcium was imbedded in the structure while micrographs of Terra-Bond treated samples showed the appearance of an epoxy material on the surface. The epoxy material appears to be responsible for encapsulating and reducing the leachability ofarsenic. XANES spectra for the PFL treatment of CCA-containing samples showed that arsenic has a predominant pentavalent form (As +5), and the PFL treatment process did not alter the arsenic oxidation state. But, distinct differences were observed for XANES spectra of untreated and PFL treated scorodite-rich mine tailing which changed the arsenic coordination structure from a mixture of As (+3/+5) to exclusively As (+5). Both S/S techniques reduced the amount of arsenic released in the leaching tests. Most cases show lower amounts of arsenic released from wastes treated by the Terra-Bond™ technique when compared to the PFL technique. The pH of the solution significantly affected the leachability, with the amount ofarsenic released increasing with pH. Sequential extraction results indicate that sodium hydroxide was favorable in releasing arsenic in the mine tailings. This is due to ligand displacement reactions of hydroxyl ions with arsenic species and high pH conditions that prevent the readsorption ofarsenic.

Bioaccessibility of total arsenic and arsenic species in seafood as determined by a continuous online leaching method.

Anal Bioanal Chem. 2012 Mar;402(9):2849-59. 
Leufroy A, Noël L, Beauchemin D, Guérin T. 
Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail, Laboratoire de Sécurité des Aliments de Maisons-Alfort, unité des Contaminants Inorganiques et Minéraux de l'Environnement, ANSES, Maisons-Alfort, Paris, France. 
Abstract - A continuous leaching method coupled online with inductively coupled plasma mass spectrometry (ICP-MS) detection was used to assess the maximum bioaccessibility of arsenic (As) in seafood samples. The method simulates continuous-flow digestion by successively pumping artificial saliva, gastric and intestinal juices through a mini-column of powdered sample directly connected to the nebuliser of an ICP-MS instrument. The method allows the real-time measurement of As being released by a given reagent. Because the analyte is continuously removed from the system, in contrast to batch methods, the dissolution equilibrium is driven to the right, hence quickly providing information about the worst-case scenario. Following consecutive leaching by the digestive reagents, the leachates were subject to speciation analysis by ion-exchange chromatography with ICP-MS detection to determine the arsenic species released. Finally, the remaining residue from the mini-column was fully digested to verify mass balance. The method was used to determine the bioaccessibility of total As and As species in four certified reference materials and in several real seafood samples. The mass balance was verified in each case. Generally speaking, the non-toxic form was easily released whereas the inorganic forms were poorly bioaccessible.

A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire.

Toxicol Lett. 2012 Apr 5;210(1):100-6. 
Lesseur C, Gilbert-Diamond D, Andrew AS, Ekstrom RM, Li Z, Kelsey KT, Marsit CJ, Karagas MR.
Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA. 
Abstract - Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenicmetabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5-20.2; P for interaction=0.03] and AQP3 Phe130Phe carriers had an OR=2.2 (95% CI: 0.8-6.1; P for interaction=0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1 Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations.

Major intrinsic proteins and arsenic transport in plants: new players and their potential role.

Adv Exp Med Biol. 2010;679:111-25. 
Bienert GP, Jahn TP. 
Unité de Biochimie Physiologique, Institut des Sciences de la Vie, Université catholique de Louvain, Croix du Sud 5-15, B-1348 Louvain-la-Neuve, Belgium. 
Abstract - Arsenic (As) is a toxic and highly abundant metalloid that endangers human health through drinking water and the food chain. The most common forms of As in the environment re arsenate [As(V)] and arsenite [As(III)]. As(V) is a nonfunctional phosphate analog that enters the food chain via plant phosphate transporters. Recently, evidence was provided that uptake of As(III)--the second most abundant As species in soils--is mediated by plant nodulin26-like intrinsic proteins (NIPs), a subfamily of plant major intrinsic proteins (MIPs). Specific NIPs are also essential for the uptake of the metalloids boron and silicon and aquaglyceroporins from microbes and mammals were shown to be the major routes of As uptake. Therefore As(III) transport through MIPs is a conserved and ancient feature. In this chapter we summarize the current view on As transport in plants and address the potential physiological significance of As(III) transport through NIPs.

In vitro study of transporters involved in intestinal absorption of inorganic arsenic.

Chem Res Toxicol. 2012 Feb 20;25(2):446-53. 
Calatayud M, Barrios JA, Vélez D, Devesa V. 
Instituto de Agroquímica y Tecnología de Alimentos (CSIC) , Av. Agustín Escardino, 7, 46980 Paterna, Valencia, Spain. 
Abstract - Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs.

A sensitive and selective fluorescence sensor for the detection of arsenic(III) in organic media.

Inorg Chem. 2012 Feb 6;51(3):1213-5. 
Ezeh VC, Harrop TC. 
Department of Chemistry, The University of Georgia, 1001 Cedar Street, Athens, Georgia 30602, United States. 
Abstract - Arsenic contamination is a leading environmental problem. As such, levels of this toxic metalloid must be constantly monitored by reliable and low-cost methodologies. Because the currently accepted upper limit for arsenic in water is 10 ppb, very sensitive and selective detection strategies must be developed. Herein we describe the synthesis and characterization of a fluorescent chemical probe, namely, ArsenoFluor1, which is the first example of a chemosensor for As(3+) detection in organic solvents at 298 K. AF1 exhibits a 25-fold fluorescence increase in the presence of As(3+) at λ(em) = 496 nm in THF, which is selective for As(3+) over other biologically relevant ions (such as Na(+), Mg(2+), Fe(2+), and Zn(2+)) and displays a sub-ppb detection limit.

Long-term impact of arsenic in drinking water on bladder cancer health care and mortality rates 20 years after end of exposure.

J Urol. 2012 Mar;187(3):856-61. 
Fernández MI, López JF, Vivaldi B, Coz F. 
Department of Urology, Hospital Militar, Santiago de Chile, Chile. 
PURPOSE: In this study we assessed bladder cancer health care and mortality trends in recent decades in a well studied arsenic exposed area in Northern Chile. MATERIALS AND METHODS: Arsenic levels in the affected region were obtained for the last 60 years, and correlated with bladder cancer hospital discharge and mortality rates in recent decades. RESULTS: Bladder cancer hospital discharge rates were significantly higher in the affected region (peak RR 3.6, 95% CI 3.0-4.7). Mortality rates for bladder cancer showed a trend of increase during the period analyzed, reaching peak mortality rates of 28.4 per 100,000 for men and 18.7 per 100,000 for women in the last 10 years. Poisson regression models showed an increased mortality risk in the studied region compared to the rest of the country until the present for men (IRR 5.3, 95% CI 4.8-5.8) and women (IRR 7.8, 95% CI 7.0-8.7). Mean age at cancer specific death was significantly lower in the exposed region (69.6 years, 95% CI 68.4-70.7 vs 73.7 years, 95% CI 73.3-74.2, p < 0.01). CONCLUSIONS: Exposure to arsenic is related to a significant need for bladder cancer health care and to high mortality rates even 20 years after having controlled arsenic levels in drinking water. Affected individuals should be aware of the significant impact of this ecological factor. Further research is required to identify strategies for the management of bladder cancer in arsenic exposed populations.

Arsenic as a food chain contaminant: mechanisms of plant uptake and metabolism and mitigation strategies.

Annu Rev Plant Biol. 2010;61:535-59. 
Zhao FJ, McGrath SP, Meharg AA. 
Rothamsted Research, Harpenden, Hertfordshire, United Kingdom. 
Abstract - Arsenic (As) is an environmental and food chain contaminant. Excessive accumulation of As, particularly inorganic arsenic (As(i)), in rice (Oryza sativa) poses a potential health risk to populations with high rice consumption. Rice is efficient at As accumulation owing to flooded paddy cultivation that leads to arsenite mobilization, and the inadvertent yet efficient uptake of arsenite through the silicon transport pathway. Iron, phosphorus, sulfur, and silicon interact strongly with As during its route from soil to plants. Plants take up arsenate through the phosphate transporters, and arsenite and undissociated methylated As species through the nodulin 26-like intrinsic (NIP) aquaporin channels. Arsenate is readily reduced to arsenite in planta, which is detoxified by complexation with thiol-rich peptides such as phytochelatins and/or vacuolar sequestration. A range of mitigation methods, from agronomic measures and plant breeding to genetic modification, may be employed to reduce As uptake by food crops.

First evidence on different transportation modes of arsenic and phosphorus in arsenic hyperaccumulator Pteris vittata.

Environ Pollut. 2012 Feb;161:1-7. 
Lei M, Wan XM, Huang ZC, Chen TB, Li XW, Liu YR. 
Center for Environmental Remediation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China. 
Abstract - Arsenic (As) reduction and translocation are key processes for As hyperaccumulation by the hyperaccumulator Pteris vittata L. Micro-X-ray adsorption spectroscopy of P. vittata's rhizoid tissues revealed that As reduction mainly occurred in endodermis during translocation from epidermis to vascular bundle. Prior to reduction, arsenate (As (V)) translocation was an active process requiring energy and employing a phosphate (P) transporter. Use of a synchrotron X-ray microprobe showed that As (V) and P were cotransported and that this process could be enhanced by As (V) exposure or P deficiency but restrained by energy release inhibition caused by 2,4-dinitrophenol or sodium orthovanadate. In contrast, after As reduction, As(III) translocation differed from P translocation and was more efficient, appearing free from the apparent endodermal blockage. The results here revealed the role of the P transporter on As translocation as well as the key role of As reduction in As hyperaccumulation by P. vittata.

A sensing array of radically coupled genetic 'biopixels'.

Nature. 2011 Dec 18;481(7379):39-44. 
Prindle A, Samayoa P, Razinkov I, Danino T, Tsimring LS, Hasty J. 
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA. 
Abstract - Although there has been considerable progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behaviour, which can hinder functionality at the colony level. Here we engineer the synchronization of thousands of oscillating colony 'biopixels' over centimetre-length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signalling between colonies. We use this platform to construct a liquid crystal display (LCD)-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as Escherichia coli, the ability to coordinate their behaviour over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field.

Variation of As concentration between soil types and rice genotypes and the selection of cultivars for reducing As in the diet.

Chemosphere. 2012 Apr;87(4):384-9. 
Ye XX, Sun B, Yin YL. 
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China. 
Abstract - Human exposure to toxic heavy metals via the food chain is of increasing concern. In the present study, the effects of soil type and genotype on variation in arsenic (As) concentrations of different organs were investigated by using nine rice cultivars grown in two soils, with two levels of As contamination. There were significant genotypic differences (P < 0.05) in As concentrations of all organs, and As concentrations of polished grain were significantly affected by genotype and soil type. The As concentration in polished grain was higher in red paddy soil under As treatment, with range from 0.24 to 1.03 mg kg(-1), and the As concentration of three cultivars exceeded the concentration of Chinese Food Hygiene Standard (0.7 mg kg(-1)). The As concentrations in stems, leaves and polished grain were all significantly and positively correlated. The As concentrations in polished grain were positively and significantly (P < 0.01) correlated with As root-grain translocation factor. The results indicated that As concentration in grain was partially governed by As uptake and the transfer of As from root to grain. The grain As concentration of the nine cultivars was significantly correlated between the two soil types at different levels of As contamination. Some genotypes, such as japonica rice (e.g. Ning jing 1 and Nan jing 32) had consistently low grain As concentrations. The results suggest the possibility of breeding the As rice cultivars to produce grain for safe consumption from soils with slight and moderate levels of As.

Monitoring of environmental arsenic by cultures of the photosynthetic bacterial sensor illuminated with a near-infrared light emitting diode array.

J Microbiol Biotechnol. 2011 Dec;21(12):1306-11. 
Maeda I, Sakurai H, Yoshida K, Siddiki M, Shimizu T, Fukami M, Ueda S. 
Faculty of Agriculture, Utsunomiya University, 350 Minemachi, Utsunomiya 321-8505, Japan. 
Abstract - Recombinant Rhodopseudomonas palustris, harboring the carotenoid-metabolizing gene crtI (CrtIBS), and whose color changes from greenish yellow to red in response to inorganic As(III), was cultured in transparent microplate wells illuminated with a light emitting diode (LED) array. The cells were seen to grow better under near-infrared light, when compared with cells illuminated with blue or green LEDs. The absorbance ratio of 525 to 425 nm after cultivation for 24 h, which reflects red carotenoid accumulation, increased with an increase in As(III) concentrations. The detection limit of cultures illuminated with near-infrared LED was 5 microgram/l, which was equivalent to that of cultures in test tubes illuminated with an incandescent lamp. A near-infrared LED array, in combination with a microplate, enabled the simultaneous handling of multiple cultures, including CrtIBS and a control strain, for normalization by the illumination of those with equal photon flux densities. Thus, the introduction of a near-infrared LED array to the assay is advantageous for the monitoring of arsenic in natural water samples that may contain a number of unknown factors and, therefore, need normalization of the reporter event.

Health implications of the distribution of arsenic species in airborne particulate matter.

J Inorg Biochem. 2012 Mar;108:112-4. 
Sanchez-Rodas D, de la Campa AS, Oliveira V, de la Rosa J. 
Department of Chemistry and Materials Science, Faculty of Experimental Sciences, Campus El Carmen, University of Huelva, Huelva, Spain. 
Abstract - Airborne particle samples were taken between 2001 and 2008 at an urban site (Huelva) in southwestern Spain. Arsenic was found in the samples due to the presence of a near-by copper smelter, sometimes at concentrations above the target value of 6 ng m(-3) proposed by EU regulations (annual means from 4.6 to 10.4 ng As m(-3) in PM10, and 3.0 to 9.1 ng As m(-3) in PM2.5). The results obtained by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) showed that arsenic accumulates preferentially (ca. 70-80%) in the particles with smaller diameter (PM2.5 versus PM10), representing a threat to human health due to the higher capacity of the finer particles to enter the organism through the respiratory system. Moreover, the toxicity of the inorganic arsenic species depends also on the oxidation state, As(III) being more toxic that As(V). The speciation analysis performed with High Performance Liquid Chromatography-Hydride Generation- Atomic Fluorescence Spectrometry (HPLC-HG-AFS) with samples collected between 2006 and 2008, showed that As(V) represented the main arsenic species, but As(III) was also found at significant concentration, representing a 5-10% of the total arsenic content. The results also indicate that the more toxic As(III) tends to concentrate preferentially in the finer fraction PM2.5 in comparison with As(V), thus representing an added health risk for the local population.

Arsenic levels in the soil and risk of birth defects: a population-based case-control study using GIS technology.

J Environ Health. 2011 Nov;74(4):20-5. 
Wu J, Chen G, Liao Y, Song X, Pei L, Wang J, Zheng X. 
Abstract - Arsenic is a highly dangerous metal that has been linked to a number of adverse health effects in both adults and children, including birth defects. Yet few epidemiologic studies have examined the relationship between arsenic levels in the soil and the risk of birth defects. The purpose of the authors' study was to examine this association among people exposed to environmental pollution in a developed area of China. The authors used global positioning system to locate the coordinates of 80 villages in 40 towns for soil sampling. Soil samples were analyzed for arsenic content. Logistic regression was used to investigate the relationship between exposure to arsenic and birth defects, controlling for potentially confounding factors. The authors found that exposure to arsenic in any amount increased the risk of birth defects. The positive association found between arsenic exposure and birth defects warrants further study, and future large-scale population-based studies are needed with an emphasis on individual-level exposure and confounding variables.

Arsenic bioaccessibility in a gold mining area: a health risk assessment for children.

Environ Geochem Health. 2012 Aug;34(4):457-65. 
Ono FB, Guilherme LR, Penido ES, Carvalho GS, Hale B, Toujaguez R, Bundschuh J. 
Department of Soil Science, Federal University of Lavras, CP 3037, Campus UFLA, Lavras, MG 37200-000, Brazil. 
Abstract - High concentrations of total arsenic (As) have been measured in soils of gold mining areas of Brazil. However, bioaccessibility tests have not yet been conducted on those materials, which is essential for better health risk estimates. This study aimed at evaluating As bioaccessibility in samples from a gold mining area located in Brazil and assessing children's exposure to As-contaminated materials. Samples were collected from different materials (a control and four As-contaminated soils/sediments) found in a gold mine area located in Paracatu (MG), Brazil. Total and bioaccessible As concentrations were determined for all samples. The control soil presented the lowest As concentrations, while all other materials contained high total As concentrations (up to 2,666 mg kg(-1)) and low bioaccessible As percentage ( < 4.2%), indicating a low risk from exposure of resident children next to this area. The calculated dose of exposure indicated that, except for the pond tailings, in all other areas, the exposure route considering soil ingestion contributed at most to 9.7% of the maximum As allowed ingestion per day (0.3 μg kg(-1) BW day(-1)).

A biography of arsenic and medicine in Hong Kong and China.

Hong Kong Med J. 2011 Dec;17(6):507-13. 
Au WY. 
University Medicine Unit, Queen Mary Hospital, Pokfulam Road, Hong Kong. 
Abstract - Arsenic trioxide has been used in traditional Chinese medicine for over 5000 years, but lost its appeal due to its toxicity. It was rediscovered in western medicine and enjoyed a renaissance from 1830 to 1930, as the first effective chemotherapy against syphilis, parasites and leukaemia. These years were also a time of political turmoil in China. The Nanking treaty (29 August 1842) turned Hong Kong into a colony, while the Xinhai Revolution (10 October 1911) gave birth to a republic of China. Arsenic returned to China and Hong Kong with the establishment of the first medical schools from 1887 to 1920. Until 1950, oral arsenic trioxide was the standard anti-leukaemic treatment in Queen Mary Hospital. The advent of alkylating chemotherapeutic agents replaced arsenic trioxide in Hong Kong and around the world. In the 1970s, however, the specific activity of arsenic trioxide against acute promyelocytic leukaemia was re-discovered during the Cultural Revolution in Harbin, China. In 1997, Hong Kong was returned to China. In the same year, arsenic trioxide returned to the world stage. Intravenous arsenic trioxide became the worldwide standard therapy for relapsed acute promyelocytic leukaemia. Oral administration of arsenic trioxide was revived in Hong Kong in 2000. This resulted in the first locally produced, registered, patented prescription drug in Hong Kong. Pending imminent manufacture, this product is poised to revolutionise acute promyelocytic leukaemia care and may hold the key to saving the lives of acute promyelocytic leukaemia patients worldwide. The remarkable journey of arsenic in the setting of medical history of China and Hong Kong is reviewed.

Rice consumption contributes to arsenic exposure in US women.

Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20656-60. 
Gilbert-Diamond D, Cottingham KL, Gruber JF, Punshon T, Sayarath V, Gandolfi AJ, Baker ER, Jackson BP, Folt CL, Karagas MR. 
Children's Environmental Health and Disease Prevention Center at Dartmouth, Hanover, NH 03755, USA.
Abstract - Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (μg/d) were significantly associated with natural log-transformed total urinary arsenic (βrice = 0.009, βwater = 0.028, both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 μg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of > 2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States.

Arsenic exposure and hypertension: a systematic review.

Environ Health Perspect. 2012 Apr;120(4):494-500. 
Abhyankar LN, Jones MR, Guallar E, Navas-Acien A. 
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. 
 BACKGROUND: Environmental exposure to arsenic has been linked to hypertension in persons living in arsenic-endemic areas. OBJECTIVE: We summarized published epidemiologic studies concerning arsenic exposure and hypertension or blood pressure (BP) measurements to evaluate the potential relationship. DATA SOURCES AND EXTRACTION: We searched PubMed, Embase, and TOXLINE and applied predetermined exclusion criteria. We identified 11 cross-sectional studies from which we abstracted or derived measures of association and calculated pooled odds ratios (ORs) using inverse-variance weighted random-effects models. DATA SYNTHESIS: The pooled OR for hypertension comparing the highest and lowest arsenic exposure categories was 1.27 [95% confidence interval (CI): 1.09, 1.47; p-value for heterogeneity = 0.001; I(2) = 70.2%]. In populations with moderate to high arsenic concentrations in drinking water, the pooled OR was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I(2) = 76.6%) and 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I(2) = 46.6%) before and after excluding an influential study, respectively. The corresponding pooled OR in populations with low arsenicconcentrations in drinking water was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I(2) = 24.6%). A dose-response assessment including six studies with available data showed an increasing trend in the odds of hypertension with increasing arsenic exposure. Few studies have evaluated changes in systolic and diastolic BP (SBP and DBP, respectively) measurements by arsenic exposure levels, and those studies reported inconclusive findings. CONCLUSION: In this systematic review we identified an association between arsenic and the prevalence of hypertension. Interpreting a causal effect of environmental arsenic on hypertension is limited by the small number of studies, the presence of influential studies, and the absence of prospective evidence. Additional evidence is needed to evaluate the dose-response relationship between environmental arsenic exposure and hypertension.

Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of seafood.

Environ Res. 2012 Jan;112:28-39. 
Molin M, Ulven SM, Dahl L, Telle-Hansen VH, Holck M, Skjegstad G, Ledsaak O, Sloth JJ, Goessler W, Oshaug A, Alexander J, Fliegel D, Ydersbond TA, Meltzer HM. 
Department of Health, Nutrition and Management, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, P.O. 4, St. Olavs Plass, NO-0130 Oslo, Norway. 
Abstract - Seafood is the predominant food source of several organoarsenic compounds. Some seafood species, like crustaceans and seaweed, also contain inorganic arsenic (iAs), a well-known toxicant. It is unclear whether human biotransformation of ingested organoarsenicals from seafood result in formation of arsenicals of health concern. The present controlled dietary study examined the urinary excretion of arsenic compounds (total arsenic(tAs), iAs, AB (arsenobetaine), dimethylarsinate (DMA) and methylarsonate (MA)) following ingestion of a single test meal of seafood (cod, 780 μg tAs, farmed salmon, 290 μg tAs or blue mussel, 690 μg tAs or potato (control, 110 μg tAs)) in 38 volunteers. The amount of ingested tAs excreted via the urine within 0-72 h varied significantly among the groups: Cod, 74% (52-92%), salmon 56% (46-82%), blue mussel 49% (37-78%), control 45% (30-60%). The estimated total urinary excretion of AB was higher than the amount of ingested AB in the blue mussel group (112%) and also ingestion of cod seemed to result in more AB, indicating possible endogenous formation of AB from other organoarsenicals. Excretion of iAs was lower than ingested (13-22% of the ingested iAs was excreted in the different groups). Although the ingested amount of iAs+DMA+MA was low for all seafood groups (1.2-4.5% of tAs ingested), the urinary DMA excretion was high in the blue mussel and salmon groups, counting for 25% and 11% of the excreted tAs respectively. In conclusion our data indicate a possible formation of AB as a result of biotransformation of other organic arsenicals. The considerable amount of DMA excreted is probably not only due to methylation of ingested iAs, but due to biotransformation of organoarsenicals making it an inappropriate biomarker of iAs exposure in populations with a high seafood intake.

Arsenic exposure in Latin America: biomarkers, risk assessments and related health effects.

Sci Total Environ. 2012 Jul 1;429:76-91. 
McClintock TR, Chen Y, Bundschuh J, Oliver JT, Navoni J, Olmos V, Lepori EV, Ahsan H, Parvez F. 
New York University School of Medicine, New York University, New York, NY, USA. 
Abstract - In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries. It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (>50 μg/L), some to as high as 2000 μg/L--200 times higher than the World Health Organization (WHO) provisional standard for drinking water. We conducted a systematic review of 82 peer reviewed papers and reports to fully explore the current understanding of As exposure and its health effects, as well as the influence of genetic factors that modulate those effects in the populations of Latin America. Despite some methodological limitations, these studies suggested important links between the high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America--including internal and external cancers, reproductive outcomes, and childhood cognitive function. Several studies demonstrated genetic polymorphisms that influence susceptibility to these and other disease states through their modulation of As metabolism, with As methyltransferase (AS3MT), glutathione S-transferase (GST), and genes of one-carbon metabolism being specifically implicated. While the full extent and nature of the health burden are yet to be known in Latin America, these studies have significantly enriched knowledge of As toxicity and led to subsequent research. Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts.

Arsenic in the human food chain: the Latin American perspective.

Sci Total Environ. 2012 Jul 1;429:92-106. 
Bundschuh J, Nath B, Bhattacharya P, Liu CW, Armienta MA, Moreno López MV, Lopez DL, Jean JS, Cornejo L, Lauer Macedo LF, Filho AT. 
Faculty of Engineering and Surveying, University of Southern Queensland, Toowoomba, Queensland 4350, Australia. 
Abstract - Many regions of Latin America are widely reported for the occurrence of high arsenic (As) in groundwater and surface water due to a combination of geological processes and/or anthropogenic activities. In this paper, we review the available literature (both in English and Spanish languages) to delineate human As exposure pathways through the food chain. Numerous studies show that As accumulations in edible plants and crops are mainly associated with the presence of high As in soils and irrigation waters. However, factors such as As speciation, type and composition of soil, and plant species have a major control on the amount of As uptake. Areas of high As concentrations in surface water and groundwater show high As accumulations in plants, fish/shellfish, livestock meat, milk and cheese. Such elevated As concentrations in food may result in widespread health risks to local inhabitants, including health of indigenous populations and residents living close to mining industries. Some studies show that As can be transferred from the water to prepared meals, thereby magnifying the As content in the human diet. Arsenic speciation might also change during food preparation, especially during high temperature cooking, such as grilling and frying. Finally, the review of the available literature demonstrates the necessity of more rigorous studies in evaluating pathways of As exposure through the human food chain in Latin America.

The relationship between obesity, insulin and arsenic methylation capability in Taiwan adolescents.

Sci Total Environ. 2012 Jan 1;414:152-8. 
Su CT, Lin HC, Choy CS, Huang YK, Huang SR, Hsueh YM. 
Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan. 
PURPOSE: This study evaluated the arsenic methylation profile of adolescents and explored the influence of body mass index (BMI) on the arsenicmethylation profile of adolescents in an area of Taiwan with no-obvious arsenic exposure. METHODS: This study evaluated 202 normal weight students and 101 obese students from eight elementary schools, recruited from September 2009 to December 2009. Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA(5+)) and dimethylarsinic acid (DMA(5+)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. RESULTS: Urinary total arsenic was significantly decreased with increasing BMI, indicating that obese children may retain higher levels of arsenic in the body, as compared to normal weight children. Participants with obesity accompanied by high insulin levels had higher inorganic arsenic, significantly higher MMA percentage and significantly lower DMA percentage than those with obesity and low insulin levels. It seems children with obesity and high insulin levels had lower arsenic methylation capacity than those with obesity and low insulin. CONCLUSIONS: This is the first study to demonstrate that total urinary arsenic is negatively associated with the BMI in adolescents in Taiwan, adjusted for age and sex. Obese adolescents with high insulin levels had significantly higher MMA% and significantly lower DMA% than obese adolescents with low insulin.

GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer's disease: association hypothesis for an uncommon genetic variant.

Neurosci Lett. 2012 Jan 11;506(2):203-7. 
Piacentini S, Polimanti R, Squitti R, Mariani S, Migliore S, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M. 
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133, Rome, Italy. 
Abstract - Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimer's Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P=0.003; adjusted OR=3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1β activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.

Inclusion of soil arsenic bioaccessibility in ecological risk assessment and comparison with biological effects.

Sci Total Environ. 2011 Dec 15;412-413:132-7. 
Saunders JR, Knopper LD, Koch I, Reimer KJ. 
Stantec Consulting Ltd. St. John's, Newfoundland, Canada. 
Abstract - The purpose of this study was to conduct an ecological risk assessment (ERA) for meadow voles (Microtus pennsilvanicus) found at three arsenic contaminated sites in Nova Scotia, Canada (as well as two background locations) and to compare the numeric results to measured biomarkers of exposure and effect. The daily intake of arsenic by meadow voles was determined by three separate calculations: estimated daily intake (EDI), bioaccessible estimated daily intake (BEDI, with bioaccessibility of soil included), and actual daily intake (ADI, which is calculated with arsenic concentrations in the stomach contents). The median bioaccessibility of arsenic in soils from the contaminated locations was significantly greater than at background locations. The bioaccessible arsenic concentration in soil from all samples (both contaminated and background) was significantly less than the total concentration. Use of site-specific bioaccessibility (hazard quotients=38 at Upper Seal Harbour (USH); 60 at Lower Seal Harbour (LSH); and 120 at Montague tailings (MONT)) and stomach arsenic contents (hazard quotients=2.1 at USH; 7.9 at LSH; and 6.7 at MONT) in the ERA resulted in lower numeric risk than compared to risk calculated with 100% bioavailability (hazard quotient=180 at USH; 75 at LSH; and 680 at MONT). Further, the use of bioaccessibility on the calculation of risk was aligned with biomarker results (changes in glutathione and micronucleated erythrocytes) in voles captured at the sites. This study provides evidence that using site-specific bioaccessibility in ERAs may provide a more realistic level of conservatism, thereby enhancing the accuracy of predicting risk to wildlife receptors. Furthermore, when numeric risk assessments are combined with site-specific biological data (i.e., biomarkers of exposure and effect), both lines of evidence can be used to make informed decisions about ecological risk and site management.