Monday, May 16, 2011

Arsenic in the aetiology of cancer.

Mutat Res. 2006 Jun;612(3):215-46. Epub 2006 Mar 29.
Tapio S, Grosche B.
Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Abstract: Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.

Assessing the genotoxic potentials of arsenic in tilapia (Oreochromis mossambicus) using alkaline comet assay and micronucleus test.

Chemosphere. 2011 Mar 5. [Epub ahead of print]
Ahmed MK, Habibullah-Al-Mamun M, Hossain MA, Arif M, Parvin E, Akter MS, Khan MS, Islam MM.
Department of Fisheries, University of Dhaka, Dhaka-1000, Bangladesh.
Abstract: This experiment was conducted to study the genotoxic potentials of sodium arsenite (NaAsO(2)) in freshwater fish Oreochromis mossambicus by using alkaline comet assay and micronucleus (MN) test. Fish were exposed to three different concentrations (3ppm, 28ppm and 56ppm) of arsenic and gill, liver and blood tissue samples were collected after 48h, 96h and 192h of exposure. Arsenic exposure induced DNA damage in all tissues examined in a concentration dependent manner. A significant (p<0.05) increase in the comet tail DNA (%) of the exposed fish liver, gill, and blood was observed after 48h and 96h of exposure, but a decline in DNA damage was recorded in all the tissues at all the three concentrations studied after 192h of exposure. Liver tissue exhibited significantly (p<0.05) higher DNA damage at all the concentrations examined, followed by gill and blood. Higher liver tail DNA (51.38±0.21%) refers that it is more prone to injury to arsenic toxicity than the gill and blood. In blood samples arsenic induced micronucleus formation in a concentration dependent manner and highest (5.8±0.46%) value was recorded in 56ppm after 96h of exposure, whereas, it was decreased after 192h of exposure at all the three concentrations of NaAsO(2) examined which refers to the DNA repairing ability of fish to arsenic toxicity. The results of this study depict the genotoxic potentials of arsenic to fish which in turns provide insight on advanced study in aquatic toxicology.

Inhalable Metal-rich Air Particles and Histone H3K4 Dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers.

Environ Health Perspect. 2011 Mar 8. [Epub ahead of print]
Cantone L, Nordio F, Hou L, Apostoli P, Bonzini M, Tarantini L, Angelici L, Bollati V, Zanobetti A, Schwartz J, Bertazzi PA, Baccarelli A.
Università degli Studi di Milano e Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena.
Abstract: BACKGROUND: Epidemiology investigations have linked exposure to ambient and occupational air particles with increased risk of lung cancer. Air particles contain carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in-vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of air particles induces histone modifications in human subjects is undetermined. OBJECTIVES: We investigated whether the metal components of air particles determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich particles. METHODS: We determined histone H3K4 dimethylation (H3K4me2) and H3K9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron), and to total particulate matter (PM), was estimated for each study subject. RESULTS: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend=0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel (β=0.16; %95 CI 0.03 to 0.3), arsenic (β=0.16; %95 CI 0.02 to 0.3), and iron (β=0.14; %95 CI 0.01 to 0.26). H3K9ac showed non-significant positive associations with air levels of nickel (β=0.24; %95 CI -0.02 to 0.51), arsenic (β=0.21; %95 CI -0.06 to 0.48) and iron (β=0.22; %95 CI -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (β=0.16; %95 CI 0.01 to 0.3 for nickel; β=0.16; %95 CI 0.03 to 0.29 for arsenic) and H3K9ac (β=0.27; %95 CI 0.01 to 0.54 for nickel; β=0.28; %95 CI 0.04 to 0.51 for arsenic). CONCLUSIONS: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

Multiple metals exposure in a small-scale artisanal gold mining community.

Environ Res. 2011 Apr;111(3):463-7.
Basu N, Nam DH, Kwansaa-Ansah E, Renne EP, Nriagu JO.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Abstract: Urinary metals were characterized in 57 male residents of a small-scale gold mining community in Ghana. Chromium and arsenic exceeded health guideline values for 52% and 34%, respectively, of all participants. About 10-40% of the participants had urinary levels of aluminum, copper, manganese, nickel, selenium, and zinc that fell outside the U.S. reference range. Exposures appear ubiquitous across the community as none of the elements were associated with occupation, age, and diet.

Multielemental Analysis of Migori (Southwest, Kenya) Artisanal Gold Mine Ores and Sediments by EDX-ray Fluorescence Technique: Implications of Occupational Exposure and Environmental Impact.

Bull Environ Contam Toxicol. 2011 May;86(5):484-9. Epub 2011 Mar 20.
Odumo OB, Mustapha AO, Patel JP, Angeyo HK.
Department of Physics, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya,
Abstract: The results of heavy element profiling of the gold ores and sediments associated with the artisanal gold mining activities of the Migori gold belt of Southwestern Nyanza, Kenya, were reported in this paper. The analysis was made to assess the occupational exposure of the miners as well as to investigate the environmental impact of toxic heavy metals. Gold ores and sediments from the artisanal gold processing were sampled in four artisanal gold mining areas: Osiri A, Osiri B, Mikei and Macalder (Makalda) and analyzed for heavy elemental content using (109)Cd radioisotope excited EDXRF spectrometry technique. Analysis consisted of direct irradiating of sample pellets. The concentrations of major elements detected were: titanium (711.41-10,766.67 mg/kg); cobalt (82.65-1,010.00 mg/kg); zinc (29.90-63,210 mg/kg); arsenic (29.30-8,246.59 mg/kg); gold (14.07-73.48 mg/kg); lead (16.31-14,999.40 mg/kg) and mercury (16.10-149.93 mg/kg). The average concentration of the heavy toxic metals i.e. arsenic, lead, titanium and zinc were found to be above 50 mg/Kg as recommended by World Health Organization.

Cancer excess after arsenic exposure from contaminated milk powder.

Environ Health Prev Med. 2011 May;16(3):164-70. Epub 2010 Sep 29.
Yorifuji T, Tsuda T, Doi H, Grandjean P.
Department of Environmental Health, Harvard School of Public Health, 401 Park Drive, 3-112-12 East, Boston, MA, 02215, USA,
Abstract: OBJECTIVES: Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality. METHODS: We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals. RESULTS: Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent. CONCLUSIONS: Although dilution is present in these cohort-based data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

Arsenic affects expression and processing of amyloid precursor protein (APP) in primary neuronal cells overexpressing the Swedish mutation of human APP.

Int J Dev Neurosci. 2011 Mar 31. [Epub ahead of print]
Zarazúa S, Bürger S, Delgado JM, Jiménez-Capdeville ME, Schliebs R.
Department of Biochemistry, Faculty of Medicine, University of San Luis Potosí, Av. V. Carranza 2405, Col. Los Filtros, 78210 San Luis Potosí, S.L.P., Mexico.
Abstract: Arsenic poisoning due to contaminated water and soil, mining waste, glass manufacture, select agrochemicals, as well as sea food, affects millions of people world wide. Recently, an involvement of arsenic in Alzheimer's disease (AD) has been hypothesized (Gong and O'Bryant, 2010). The present study stresses the hypothesis whether sodium arsenite, and its main metabolite, dimethylarsinic acid (DMA), may affect expression and processing of the amyloid precursor protein (APP), using the cholinergic cell line SN56.B5.G4 and primary neuronal cells overexpressing the Swedish mutation of APP, as experimental approaches. Exposure of cholinergic SN56.B5.G4 cells with either sodium arsenite or DMA decreased cell viability in a concentration- and exposure-time dependent manner, and affected the activities of the cholinergic enzymes acetylcholinesterase and choline acetyltransferase. Both sodium arsenite and DMA exposure of SN56.B5.G4 cells resulted in enhanced level of APP, and sAPP in the membrane and cytosolic fractions, respectively. To reveal any effect of arsenic on APP processing, the amounts of APP cleavage products, sAPPβ, and β-amyloid (Aβ) peptides, released into the culture medium of primary neuronal cells derived from transgenic Tg2576 mice, were assessed by ELISA. Following exposure of neuronal cells by sodium arsenite for 12h, the membrane-bound APP level was enhanced, the amount of sAPPβ released into the culture medium was slightly higher, while the levels of Aβ peptides in the culture medium were considerably lower as compared to that assayed in the absence of any drug. The sodium arsenite-induced reduction of Aβ formation suggests an inhibition of the APP γ-cleavage step by arsenite. In contrast, DMA exposure of neuronal cells considerably increased formation of Aβ and sAPPβ, accompanied by enhanced membrane APP level. The DMA-induced changes in APP processing may be the result of the enhanced APP expression. Alternatively, increased Aβ production may also be due to stimulation of caspase activity by arsenic compounds, or failure in Aβ degradation. In summary, the present report clearly demonstrates that sodium arsenite and DMA affect processing of APP in vitro.

Atmospheric arsenic (As) study at five characteristic sampling sites in Taiwan.

Environ Monit Assess. 2011 Mar 30. [Epub ahead of print]
Fang GC, Huang YL, Huang JH.
Department of Safety, Health and Environmental Engineering, HungKuang University, Sha-Lu, Taichung, 433, Taiwan,
Abstract: The main purpose for this study is to observe the seasonal and monthly variations for arsenic (As) in total suspended particulates (TSP) concentration and dry deposition at five characteristic sampling sites during the years 2009 and 2010 in central Taiwan. The results show that the highest and lowest monthly average As concentrations in TSP occurred in January and May at Bei-shi (suburban/coastal) and Quan-xing (industrial) sampling sites. In addition, the results show that the highest and lowest monthly average As dry deposition occurred in October and May at Chang-hua (downtown) and Gao-mei (wetland) sampling sites. This study reflected that the mean highest As concentrations in TSP and mean highest As dry deposition occurred at Quan-xing (industrial). However, the mean lowest As concentrations in TSP and mean lowest As dry deposition also occurred at Gao-mei (wetland). Regarding seasonal variation, the results show that the As average seasonal concentration order in TSP was winter > spring > fall > summer, respectively, at Chang-hua (downtown) and He-mei (residential) sampling sites. Finally, the order of As average seasonal dry deposition was fall > winter > spring > summer, respectively, at Chang-hua (downtown), He-mei (residential), and Gao-mei (wetland) sampling sites.

Probability of intellectual disability is associated with soil concentrations of arsenic and lead.

Chemosphere. 2011 Mar 28. [Epub ahead of print]
McDermott S, Wu J, Cai B, Lawson A, Marjorie Aelion C.
University of South Carolina, School of Medicine, Department of Family and Preventive Medicine, 3209 Colonial Drive, Columbia, SC 29203, United States.
Abstract: BACKGROUND: The association between metals in water and soil and adverse child neurologic outcomes has focused on the singular effect of lead (Pb), mercury (Hg), and arsenic (As). This study describes the complex association between soil concentrations of As combined with Pb and the probability of intellectual disability (ID) in children. METHODS: We used a retrospective cohort design with 3988 mother child pairs who were insured by Medicaid and lived during pregnancy and early childhood in South Carolina between 1/1/97 and 12/31/02. The children were followed until 6/1/08, using computerized service files, to identify the diagnosis of ID in medical records and verified by either school placement or disability service records. The soil was sampled using a uniform grid and analyzed for eight metals. The metal concentrations were interpolated using Bayesian Kriging to estimate concentration at individual residences. RESULTS: The probability of ID increased for increasing concentrations of As and Pb in the soil. The Odds Ratio for ID, for one unit change in As was 1.130 (95% confidence interval 1.048-1.218) for Pb was 1.002 (95% confidence interval 1.000-1.004). We identified effect modification for the infants based on their birth weight for gestational age status and only infants who were normal size for their gestational age had increased probability of ID based on the As and Pb soil concentrations (OR for As at normal weight for gestational age=1.151 (95% CI: 1.061-1.249) and OR for Pb at normal for gestational age=1.002 (95% CI: 1.002-1.004)). For normal weight for gestational age children when As=22mgkg(-1) and Pb=200mgkg(-1) the risk for ID was 11% and when As=22mgkg(-1)and Pb=400mgkg(-1) the probability of ID was 65%. CONCLUSION: The probability of ID is significantly associated with the interaction between Pb and As for normal weight for gestational age infants.

Arsenic and manganese exposure and children's intellectual function.

Wasserman GA, Liu X, Parvez F, Factor-Litvak P, Ahsan H, Levy D, Kline J, van Geen A, Mey J, Slavkovich V, Siddique AB, Islam T, Graziano JH.
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York City, NY 10032, United States; NY State Psychiatric Institute, 1051 Riverside Drive, New York City, NY 10032, United States.
Abstract: Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10μg/L) and Mn (above and below 500μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels.

Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium.

BMC Genomics. 2011 Apr 1;12:173.
Benton MA, Rager JE, Smeester L, Fry RC.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Abstract: BACKGROUND: Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored. RESULTS: In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis. CONCLUSIONS: This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.

Atmospheric stability of arsine and methylarsines.

Environ Sci Technol. 2011 May 1;45(9):4010-5. Epub 2011 Apr 6.
Mestrot A, Merle JK, Broglia A, Feldmann J, Krupp EM.
TESLA (Trace Element Speciation Laboratory), Chemistry Department, University of Aberdeen , Aberdeen, AB24 3UE, United Kingdom.
Abstract: Arsenic (As) occurs in a variety of different chemical forms, among them volatile (gaseous) species, usually referred to as arsine and methylarsines. Here we demonstrate that arsine and methylarsines are stable in air in concentrations at the μg/L gas level. We determined half-lives of approximately 8 h under daytime conditions (UV light) for all methylated arsines, while the same species were found to be considerably more stable in night-time (dark) conditions. Arsine (AsH(3)) showed under both day and night-time conditions, considerably higher stabilities than methylated arsines. We show here that volatile As species seem stable enough to travel considerable distances in the atmosphere from a point source before converting into nonvolatile, oxidized compounds. Also, the degradation pathway leading to the conversion to nonvolatile compounds was investigated using computational chemistry. Arsine and methylarsines' reactions with the hydroxyl radical (•OH) as well as As-C and As-H bonds strengths in the species studied were modeled. Results showed that conversion could not be explained by H abstraction, nor by OH addition. Moreover, it was found that As-C and As-H bonds strengths are not the determining factor responsible for the decrease in stability with ascending methylation of the different volatile arsine species, as previously suggested.

Human risk assessment of heavy metals: principles and applications.

Met Ions Life Sci. 2011;8:27-60.
Dorne JL, Kass GE, Bordajandi LR, Amzal B, Bertelsen U, Castoldi AF, Heppner C, Eskola M, Fabiansson S, Ferrari P, Scaravelli E, Dogliotti E, Fuerst P, Boobis AR, Verger P.
European Food Safety Authority, Largo N. Palli 5, I-43100 Parma, Italy.
Abstract: Humans are exposed to a number of "heavy metals" such as cadmium, mercury and its organic form methylmercury, uranium, lead, and other metals as wel as metalloids, such as arsenic, in the environment, workplace, food, and water supply. Exposure to these metals may result in adverse health effects, and national and international health agencies have methodologies to set health-based guidance values with the aim to protect the human population. This chapter introduces the general principles of chemical risk assessment, the common four steps of chemical risk assessment: hazard identification, hazard characterization, exposure assessment, risk characterization, and toxicokinetic and toxicity aspects. Finally, the risk assessments performed by international health agencies such as the World Health Organisation, the Environmental Protection Agency of the United States, and the European Food Safety Authority are reviewed for cadmium, lead, mercury, uranium, and arsenic.

Arsenic transformations in terrestrial small mammal food chains from contaminated sites in Canada.

J Environ Monit. 2011 Apr 19. [Epub ahead of print]
Saunders JR, Hough C, Knopper LD, Koch I, Reimer KJ.
Stantec, Ottawa, Ontario K1B 1A7, Canada.
Abstract: Arsenic in terrestrial contaminated sites has the potential to cause harm to residential wildlife. The aim of this study was to determine the arsenic species in wild rodents living in arsenic contaminated habitats, specifically deer mice from Yellowknife, NT and meadow voles from Seal Harbour, NS, along with co-located plants. Methanol : water (1 : 1) extractions were used to optimize the extraction of methylated arsenic(v) species. Total arsenic concentrations were substantially higher in the Yellowknife deer mice (1.7-3.2 µg kg(-1) wet weight in livers) and Seal Harbour meadow voles (0.67-0.97 µg kg(-1) wet weight in livers) living on the contaminated sites with respect to the surrounding background locations (0.12-0.34 µg kg(-1) wet weight in livers). Around 50% of arsenic could be identified in Yellowknife deer mouse tissues, but only <10% was identified in Seal Harbour vole tissues; inorganic arsenic (iii and v) and dimethylarsinic acid were all found. Monomethylarsonic acid was only detected in both the mice and voles living in the contaminated sites. In the Yellowknife food chain, methyl arsenic (v) proportions increased from plants to mouse inner organs, but the trend was not for clear as the Seal Harbour food chain. Seal Harbour voles may be sequestering arsenic in a less mobile form, rather than transforming it.

Exposure to Moderate Arsenic Concentrations Increases Atherosclerosis in ApoE-/- Mouse Model.

Toxicol Sci. 2011 Apr 21. [Epub ahead of print]
Lemaire M, Lemarié CA, Molina MF, Schiffrin EL, Lehoux S, Mann KK.
Lady Davis Institute for Medical Research, Dept. Oncology, McGill University, Montreal, H3T 1E2, Canada.
Abstract: Arsenic is a widespread environmental contaminant to which millions of people are exposed worldwide. Exposure to arsenic is epidemiologically linked to increased cardiovascular disease, such as atherosclerosis. However, the effects of moderate concentrations of arsenic on atherosclerosis formation are unknown. Therefore, we utilized an in vivo ApoE(-/-) mouse model to assess the effects of chronic moderate exposure to arsenic on plaque formation and composition in order to facilitate mechanistic investigations. Mice exposed to 200 ppb arsenic developed atherosclerotic lesions, a lower exposure than previously reported. In addition, arsenic modified the plaque content, rendering them potentially less stable and consequently, potentially more dangerous. Moreover, we observed that the lower exposure concentration was more atherogenic than the higher concentration. Arsenic-enhanced lesions correlated with several pro-atherogenic molecular changes, including decreased LXR target gene expression and increased pro-inflammatory cytokines. Significantly, our observations suggest that chronic moderate arsenic exposure may be a greater cardiovascular health risk than previously anticipated.

Arsenic trioxide induces procoagulant activity through phosphatidylserine exposure and microparticle generation in endothelial cells.

Thromb Res. 2011 May;127(5):466-72. Epub 2011 Jan 26.
Zhou J, Li H, Fu Y, Shi J, Hou J, Zhang Y, Liu X, Song P.
Department of Hematology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Abstract: BACKGROUND: Coagulopathy is a major cause of early death when arsenic trioxide (As(2)O(3)) therapy fails. In addition to the procoagulant properties of blast cells, the cytotoxic therapy may contribute to the coagulation disorders. The aim of the present study was to evaluate the possible impact of As(2)O(3) on membrane alterations, including phosphatidylserine (PS) exposure and microparticle generation, and the consequent procoagulant properties of endothelial cells. METHODS: Procoagulant activity (PCA) of human umbilical vein endothelial cells (HUVECs) was assessed by measuring clotting time and through purified coagulation complex assays. PS exposure on HUVEC membrane was observed by confocal microscopy and quantified with flow cytometry. In addition, counts and PCA of endothelial microparticles were determined by flow cytometry and plasma coagulation assay. RESULTS: As(2)O(3) increased the ability of HUVECs to accelerate coagulation process and promote formation of coagulation complexes. Procoagulant activity corresponded to PS exposed on HUVECs. In coincidence with the PS externalization, As(2)O(3) increased the production of PS-bearing microparticles, which then accelerated fibrin strand formation significantly. By blocking PS, lactadherin was able to inhibit over 90% of the intrinsic tenase/prothrombinase activity of As(2)O(3)-treated HUVECs, and restored coagulation times of As(2)O(3)-treated cells and microparticles to control levels. CONCLUSIONS: As(2)O(3) increases PCA of HUVECs through PS exposure and PS-bearing microparticle generation, which might cause thrombosis and act as a contributing factor in As(2)O(3) therapy-related coagulopathy.

Epigenetic changes in individuals with arsenicosis.

Chem Res Toxicol. 2011 Feb 18;24(2):165-7. Epub 2011 Feb 4.
Smeester L, Rager JE, Bailey KA, Guan X, Smith N, García-Vargas G, Del Razo LM, Drobná Z, Kelkar H, Stíyblo M, Fry RC.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, UNC-Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Abstract: Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically exposed individuals are susceptible to arsenicosis or arsenic poisoning. Using a state-of-the-art technique to map the methylomes of our study subjects, we identified a large interactome of hypermethylated genes that are enriched for their involvement in arsenic-associated diseases, such as cancer, heart disease, and diabetes. Notably, we have uncovered an arsenic-induced tumor suppressorome, a complex of 17 tumor suppressors known to be silenced in human cancers. This finding represents a pivotal clue in unraveling a possible epigenetic mode of arsenic-induced disease.

Arsenic: toxicity, oxidative stress and human disease.

J Appl Toxicol. 2011 Mar;31(2):95-107. doi: 10.1002/jat.1649. Epub 2011 Feb 14.
Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M.
Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University, Nitra, Slovakia.
Abstract: Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress.

Arsenic concentrations in soils impacted by dam failure of coal-ash pond in zemianske kostolany, slovakia.

Bull Environ Contam Toxicol. 2011 Apr;86(4):433-7. Epub 2011 Feb 18.
Jurkovič L, Hiller E, Veselská V, Pet'ková K.
Faculty of Natural Sciences, Department of Geochemistry, Comenius University in Bratislava, Mlynska dolina, 842 15, Bratislava 4, Slovak Republic.
Abstract: In this study, the concentrations of arsenic were determined in the soils around old coal-ash pond. The soils in the study area were severely contaminated with arsenic after dam failure of the coal-ash pond. The mean concentrations of arsenic in soils collected from three sampling depths of 0-20, 20-40 and >40 cm were 173, 155 and 426 μg/g, respectively, exceeding greatly the Dutch intervention threshold for this element. Arsenic concentrations were positively correlated with total iron and aluminium contents in the soils (r = 0.73, p < 0.001 and r = 0.72, p < 0.001, respectively), indicating that oxyhydroxides of iron and aluminium may control the distribution of arsenic in these soils. Ammonium nitrate extractant was used to mimic availability of arsenic for plant uptake from the soils. Between 0.05 and 6.21% of the total soil arsenic were extracted using a single extraction test and a significant positive correlation between soil leachate pH and arsenic extractability (r = 0.70, p < 0.01) was observed. This suggested that soil pH might play a role in the bioavailability of arsenic.

The Fluctuation of Arsenic Levels in Lake Taihu.

Biol Trace Elem Res. 2011 Feb 22. [Epub ahead of print]
Wei C, Zhang N, Yang L.
Institute of Geographic Sciences & Natural Resources Research, Chinese Academy of Sciences, 11A Datun Road, Chaoyang District, Beijing, 100101, China,
Abstract: This study was conducted to investigate the arsenic levels in the waters of lake Taihu, a huge, shallow, and very important lake which has been suffered with serious eutrophication in China. Unexpected great difference was detected for arsenic levels between the collected water samples of three successive surveys in Taihu in May 2009, Fall 2009, and May 2010, with arsenic levels in May 2009 being more than tenfold of those in Fall 2009 and May 2010. Such difference in arsenic levels do not routinely happen like seasonal changes as reported in many other lakes of the world. Considering arsenic contents as well as some basic aquatic monitoring data of the lake, such great arsenic fluctuations were probably due to the effects of strong hydraulic turbulence in Taihu for its very shallow depth. The spatial distribution of arsenic in Taihu were similar, despite great difference of arsenic levels in the three successive surveys, indicating such differences did not come from arsenic external input around the lake. The sudden increase of arsenic levels in Taihu highlights the importance of stabilization or removing of arsenic in lake sediments so as to keep arsenic lower than the national hygiene standard of China.

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study.

Int J Epidemiol. 2011 Feb 22. [Epub ahead of print]
Chen Y, Parvez F, Liu M, Pesola GR, Gamble MV, Slavkovich V, Islam T, Ahmed A, Hasan R, Graziano JH, Ahsan H.
Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY, USA, Section of Pulmonary Disease, Department of Medicine, Harlem Hospital, New York, NY, USA, Columbia University Arsenic Research Project, Dhaka, Bangladesh and Department of Health Studies, Medicine and Human Genetics and Cancer Research Center, The University of Chicago, Chicago, IL, USA.
Abstract: BACKGROUND: Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. METHODS: We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. RESULTS: At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤7, 8-39, 40-91, 92-179 and 180-864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77-1.27], POR 1.23 (95% CI 0.97-1.57), POR 1.50 (95% CI 1.18-1.89) and POR 1.59 (95% CI 1.26-2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67-1.03) and POR 0.91 (95% CI 0.74-1.12) for participants with a decreasing level of >70 and 17-70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97-1.42) and POR 1.42 (95% CI 1.16-1.73) for participants with an increasing level of 16-68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As -16 to 15 µg/l). CONCLUSION: The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure.

Molecular changes during arsenic-induced cell transformation.

J Cell Physiol. 2011 Feb 22. doi: 10.1002/jcp.22683. [Epub ahead of print]
Li G, Lee LS, Li M, Tsao SW, Chiu JF.
Department of Biochemistry/Open Laboratory for Tumor Molecular Biology, Shantou University Medical College, Shantou 515041, China.
Abstract: Arsenic and its derivatives are naturally occurring metalloid compounds widely distributed in the environment. Arsenics are known to cause cancers of the skin, liver, lung, kidney, and bladder. Although numerous carcinogenic pathways have been proposed, the exact molecular mechanisms remain to be delineated. To further characterize the role of oxidative stress in arsenite- induced cell transformation via the reactive oxygen species (ROS)-mediated Ras/Erk pathway, here we demonstrated arsenite-induced rat lung epithelial cell (LEC) transformation, epithelial-mesenchymal transition, stimulation of the extracellular signal-regulated kinase signaling pathway, and enhancement of cell proliferation. However, there was no evidence of activation of the phosphoinositide 3-kinase/protein kinase B pathway in arsenite-induced transformed LECs. Since ROS is involved in arsenite-induced LEC cell transformation, Redox-status regulatory proteins (Cu/Zn SOD and thioredoxin) and arsenite-induced LEC cell transformation were significantly inhibited by concurrent treatment with the antioxidants. Our experimental results clearly demonstrated that induction of p-ERK and cell proliferation by arsenite is mediated via oxidative stress, since antioxidants can inhibit arsenite-induced cell transformation.

Bioaccessibility and health risk of arsenic, mercury and other metals in urban street dusts from a mega-city, Nanjing, China.

Environ Pollut. 2011 May;159(5):1215-21. Epub 2011 Feb 22.
Hu X, Zhang Y, Luo J, Wang T, Lian H, Ding Z.
Key Lab of Analytical Chemistry for Life Science (Ministry of Education), Center of Material Analysis, Nanjing University, Nanjing 210093, Jiangsu Province, PR China.
Abstract: The oral bioaccessibility and the human health risks of As, Hg and other metals (Cu, Pb, Zn, Ni, Co, Cd, Cr, Mn, V and Fe) in urban street dusts from different land use districts in Nanjing (a mega-city), China were investigated. Both the total contents and the oral bioaccessibility estimated by the Simple Bioaccessibility Extraction Test (SBET) of the studied elements varied with street dusts from different land use districts. Cd, Zn, Mn, Pb, Hg and As showed high bioaccessibility. SBET-extractable contents of elements were significantly correlated with their total contents and the dust properties (pH, organic matter contents). The carcinogenic risk probability for As and Cr to children and adults were under the acceptable level (<1 × 10(-4)). Hazard Quotient values for single elements and Hazard Index values for all studied elements suggested potential non-carcinogenic health risk to children, but not to adults.

[Soil arsenic content and its health risk assessment for agricultural products in the region surrounding Shimen arsenic sulphide mine]. [Article in Chinese]

Ying Yong Sheng Tai Xue Bao. 2010 Nov;21(11):2946-51.
Li LF, Zeng XB, Bai LY, Li SH.
Ministry of Agriculture Key Laboratory of Agro-Environment & Climate Change, Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Abstract: A systematic investigation was carried out on the arsenic content in the soils and plants surrounding Shimen arsenic sulphide mine. The arsenic content in top soils (0-20 cm) was averagely 99.51 mg x kg(-1), being 5.34 times higher than that of the background value in Hunan Province and 8.70 times higher than that of local farmland soil. The topsoil arsenic content in paddy field and dry land was 43.51 and 115.1 mg x kg(-1), respectively, being 0.45 and 1.87 times higher than that of the grade II level (paddy field 30 mg x kg(-1); dry land 40 mg x kg(-1)) commended by the National Soil Quality (GB 15618-1995), and the corresponding arsenic exceeding rate was 62.5% and 50.0%, respectively. The arsenic content in edible parts of foodstuff, vegetables, and fruits was 0.16, 0.06, and 0.01 mg x kg(-1), respectively, and the arsenic exceeding rate of crop samples compared to food security standard ranked in the order of foodstuff > vegetables > fruits. Rice and sweet potato were relatively seriously contaminated by arsenic. The highest arsenic content of rice was up to 0.84 mg x kg(-1), which was 4.6 times higher than that of the National Standard, with the exceeding rate of 62.5%. Statistical analysis demonstrated that there was a positive correlation between the arsenic contents of soil and plant. The average daily intake of arsenic by local people through the consumption of the crops was 6.416 microg x kg(-1) x d(-1), which was much higher than the standard commended by WHO, and the related health risk index was 21.39, which was 14.39 times higher than that in the control region.

[Comunicable diseases, mental health and exposure to environmental pollutants in population living near Las Bambas mining project before exploitation phase, Peru 2006]. [Article in Spanish]

Rev Peru Med Exp Salud Publica. 2010 Oct-Dec;27(4):512-9.
Astete J, Gastañaga Mdel C, Fiestas V, Oblitas T, Sabastizagal I, Lucero M, Abadíe Jdel M, Muñoz ME, Valverde A, Suarez M.
Centro Nacional de Salud Ocupacional y Protección del Ambiente para la Salud, Instituto Nacional de Salud, Lima, Perú.
Abstract: OBJECTIVE: To determine the prevalence of communicable diseases, mental health and environmental pollutants exposure in population living near Las Bambas mining project before exploitation phase. MATERIAL AND METHODS: Cross sectional study performed in 453 subjects (children and adults) living in three Apurimac region districts: Haquira, Chalhuahuacho and Progreso. Psychomotor development, intelligence quotient, anxiety and depression levels and the presence of communicable diseases (viral hepatitis B, C and delta, syphilis and HIV) were evaluated, as well as heavy metals (lead in blood, and cadmium, arsenic and mercury in urine samples) and serum cholinesterase levels. RESULTS: Mean age was 29 ± 17.25 years, 59.2% were female and a range of 6 to 15 years of living in the area was found. No cases of HIV, hepatitis C and delta were found, 1.4% were positive for syphilis and in relation to hepatitis B, we found 1,7% of subjects positive to total anti HBc and 0.5% positive for HBsAg. Heavy metal testing identified people with exceeding limits of mercury in 1.8% arsenic in 4.6%, lead in 24.3% and cadmium in 43.9%. Besides, 29.1% of the population had cholinesterase levels below normal range. Among children, 12.5% were at psychomotor development levels of risk; 2.1% and 3.1% suffered from mild and borderline intellectual disability (mental retardation), respectively. 34.3% of subjects older than 12 had anxiety and 17.5% depression. CONCLUSIONS: Evidence of heavy metal environmental pollution and presence of communicable diseases in this population were already found. Future careless mining activity could worsen the current health situation.

Control of subterranean termites (Isoptera: Rhinotermitidae) infesting power poles.

J Econ Entomol. 2010 Dec;103(6):2140-6.
Horwood MA, Westlake T, Kathuria A.
Forest Science Centre, Industry and Investment New South Wales, P.O. Box 100 Beecroft, NSW 2119, Australia.
Abstract: A trial was conducted to determine the efficacy of termiticidal dusts (arsenic trioxide, triflumuron, and Metarhizium anisopliae), a timber fumigant (dazomet) and liquid termiticides (bifenthrin, chlorfenapyr, chlorpyrifos, fipronil, and imidacloprid) for controlling subterranean termites (Isoptera: Rhinotermitidae) infesting in-service power poles in New South Wales, Australia. Dusts were applied to parts of the pole where termites were present. Fumigant was inserted into holes drilled into the base of the pole. Liquid termiticides were mixed with soil around the base of the pole and injected into internal voids if present. Poles were inspected for up to 5 yr, and the time taken for reinfestation to occur was recorded. Before the start of the trial, the major Australian pole owners were surveyed to obtain an estimate of the annual national cost of termite infestation to the power supply industry. The annual costs of termite treatment and replacing damaged poles were estimated at AU$2 million and AU$13 million, respectively. Infestation rates were lower for all treatments compared with controls within the first 12 mo of the study. Dazomet, arsenic trioxide, fipronil, and chlorpyrifos were the most efficacious treatments. Efficacy was positively related to the amount of termiticide applied and negatively related to the infestation severity but was unaffected by geographical location. Survival curves were calculated of the time elapsed before the recurrence of termite infestations (survival absence of reinfestation). Survival was highest for poles treated with liquid termiticides.