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Arsenic (Inorganic)

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

N-6-Adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms and arsenic methylation in Andean women

Authors: Harari, F; Engström, K; Concha, G; Colque, G; Vahter, M; Broberg, K (In Press) Environmental Health Perspectives. HERO ID: 1597348

[Less] Background: In humans, inorganic arsenic is metabolized to methylated metabolites mainly by arsenic . . . [More] Background: In humans, inorganic arsenic is metabolized to methylated metabolites mainly by arsenic (+3 oxidation state) methyltransferase (AS3MT). AS3MT polymorphisms are associated with arsenic metabolism efficiency. Recently, a putative N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) was found to methylate arsenic in vitro. Objective: We evaluated the role of N6AMT1 polymorphisms in arsenic methylation efficiency in humans. Methods: We assessed arsenic methylation efficiency in 188 women exposed to arsenic via drinking water (~ 200 µg/L) in the Argentinean Andes by measuring the relative concentrations of arsenic metabolites in urine [inorganic arsenic, methylarsonic acid (MMA), and dimethylarsinic acid] by high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. We performed genotyping for N6AMT1 and AS3MT polymorphisms by Taqman assays, and gene expression (in blood; n = 63) with Illumina HumanHT-12 v4.0. Results: Five N6AMT1 single nucleotide polymorphisms (SNPs; rs1997605, rs2205449, rs2705671, rs16983411, and rs1048546) and two N6AMT1 haplotypes were significantly associated with the percentage of MMA (%MMA) in urine, even after adjusting for AS3MT haplotype. %MMA increased monotonically according to the number of alleles for each SNP (e.g., for rs1048546, mean %MMA was 7.5% for GG, 8.8% for GT, and 9.7% for TT carriers). Three SNPs were in linkage disequilibrium (R2 > 0.8). Estimated associations for joint effects of N6AMT1 (haplotype 1) and AS3MT (haplotype 2) were generally consistent with expectations for additive effects of each haplotype on %MMA. Carriers of N6AMT1 genotypes associated with lower %MMA showed the lowest N6AMT1 expression, but associations were monotonic according to copy number for only one genotype and one haplotype. Conclusions: N6AMT1 polymorphisms were associated with arsenic methylation in Andean women, independent of AS3MT. N6AMT1 polymorphisms may be susceptibility markers for arsenic-related toxic effects.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Ethanol enhances tumor angiogenesis in vitro induced by low-dose arsenic in colon cancer cells through hypoxia-inducible factor 1 alpha pathway

Authors: Wang, L; Son, Y-O; Ding, S; Wang, X; Hitron, JA; Budhraja, A; Lee, J-C; Lin, Q; Poyil, P; Zhang, Z; Luo, J; Shi, X (In Press) Toxicological Sciences. HERO ID: 1257627

[Less] Health effects due to environmental exposure to arsenic are a major global health concern. Arsenic has . . . [More] Health effects due to environmental exposure to arsenic are a major global health concern. Arsenic has been known to induce carcinogenesis and enhance tumor development via complex and unclear mechanism. Ethanol is also a well-established risk factor for many malignancies. However, little is known about the effects of co-exposure to arsenic and ethanol in tumor development. In this study, we investigate the signaling and angiogenic effect of co-exposure of arsenic and ethanol on different colon cancer cell lines. Results show that ethanol markedly enhanced arsenic-induced tumor angiogenesis in vitro. These responses are related to intracellular reactive oxygen species (ROS) generation, NAPDH oxidase activation, and up-regulation of PI3K/AKT and hypoxia-inducible factor 1 alpha (HIF-1α) signaling. We have also found that ethanol increase the arsenic-induced expression and secretion of angiogenic signaling molecules such as vascular endothelial growth factor (VEGF), which further confirmed the above observation. Antioxidant enzymes inhibited arsenic/ethanol-induced tumor angiogenesis, demonstrating that the responsive signaling pathways of co-exposure to arsenic and ethanol are related to ROS generation. We conclude that ethanol is able to enhance arsenic-induced tumor angiogenesis in colorectal cancer cells via the HIF-1α pathway. These results indicate that alcohol consumption should be taken into consideration in the investigation of arsenic-induced carcinogenesis in arsenic-exposed populations.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats

Authors: Kharroubi, W; Dhibi, M; Haouas, Z; Chreif, I; Neffati, F; Hammami, M; Sakly, R (2014) Environmental Science and Pollution Research 21:1648-1657. HERO ID: 1936064

[Less] The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity . . . [More] The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats were randomly devised to six groups (n = 10 per group) and exposed to sodium arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is associated with significant changes in the FA composition in liver. A significant increase of saturated fatty acids (SFA) in all treated groups (p < 0.01) and trans unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10 mg/l (p < 0.05) and long term for 1 and 10 mg/l (p < 0.001) was observed. However, the cis UFA were significantly decreased in these groups (p < 0.05). A markedly increase of indicator in cell membrane viscosity expressed as SFA/UFA was reported in the treated groups (p < 0.001). A significant increase in the level of malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed. Compared to control rats, significant liver damage was observed at 10 mg/l of arsenate by increasing plasma marker enzymes after 90 days. It is through the histological investigations in hepatic tissues of exposed rats that these damage effects of arsenate were confirmed. The antioxidant perturbations were observed to be more important at groups treated by the high dose (p < 0.05). An increase in the level of protein carbonyls was observed in all treated groups (p < 0.05). The present study provides evidence for a direct effect of arsenite on FA composition disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity towards liver cancer.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low doses of arsenic

Authors: Liu, Y; Hock, JM; Van Beneden, RJ; Li, X (2014) Molecular Carcinogenesis 53:380-391. HERO ID: 1453806

[Less] Environmental or occupational exposure to low doses of arsenic induces a series of health problems including . . . [More] Environmental or occupational exposure to low doses of arsenic induces a series of health problems including cancer. The molecular events in arsenic-induced carcinogenicity remain to be defined. In the NuLi-1 immortalized human lung epithelial cell line with p53 and pRb deficiency, exposure to low doses of arsenic trioxide for 72 h promoted cell proliferation and upregulated the gene transcription levels of FOXM1, CDC6, CDC25A, and cyclin D1, which are both critical cell cycle regulatory genes and proto-oncogenes. Continuous in vitro exposure to 1 µM arsenic trioxide for 34 wks induced malignant cell transformation, as evidenced by enhanced anchorage-independent cell growth. The expression of FOXM1, CDC6, CDC25A, and Cyclin D1 was dynamically elevated at the gene transcription and protein levels in the process of cell transformation. The carcinogenic ability of transformed cell colonies coincides with the expression levels of FOXM1 in in vitro anchorage-independent growth assays and in vivo tumor xenograft formation assays. In reverse, the knockdown of FOXM1 in lung adenocarcinoma A549 cells or arsenic-transformed NuLi-1 cells significantly decreased anchorage-independent cell growth and tumor xenograft formation. The transformed NuLi-1 cells showed genomic instability in the form of copy number variation (CNV) at chromosome 1, 5, 6, 18, and 20, but not loss of heterozygosity (LOH). These results showed for the first time that chronic exposure to low doses of arsenic trioxide promoted lung carcinogenicity, in part by aberrantly upregulating FOXM1 and its associated oncogenes, when the tumor suppressor genes p53 and pRb were inactivated. © 2012 Wiley Periodicals, Inc.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats

Authors: Mathews, VV; Paul, MS; Abhilash, M; Manju, A; Abhilash, S; Nair, RH (2014) Toxicology and Industrial Health. HERO ID: 1453808

[Less] Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. . . . [More] Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry

Authors: García-Sevillano, MA; Contreras-Acuña, M; García-Barrera, T; Navarro, F; Gómez-Ariza, JL (2014) Analytical and Bioanalytical Chemistry 406:1455-1469. HERO ID: 2279035

[Less] The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants . . . [More] The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants metabolism and oxidative stress may play a role. The toxicological effects of trivalent inorganic arsenic on laboratory mouse Mus musculus after oral administration (3 mg/kg body weight/day) were investigated along 12 days, using a metabolomic approach based on direct infusion mass spectrometry to polar and lipophilic extracts from different organs and fluids (liver, kidney, and plasma). Positive and negative acquisition modes (ESI(+)/ESI(-)) were used throughout the experiments. The most significant endogenous metabolites affected by exposure were traced by partial least square-discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas chromatography coupled to MS. In this work, the toxic effect of arsenic has been related with important metabolic pathways, such as energy metabolism (e.g., glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine cycle, and degradation of membrane phospholipids (cell apoptosis). In addition, this work illustrates the high reliability of mass spectrometry based on a metabolomic approach to study the biochemical effects induced by metal exposure.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas

Authors: Gong, G; Mattevada, S; O'Bryant, SE (2014) Environmental Research 130:59-69. HERO ID: 2279475

[Less] Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, . . . [More] Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Arsenic and fluoride co-exposure affects the expression of apoptotic and inflammatory genes and proteins in mononuclear cells from children

Authors: Estrada-Capetillo, BL; Ortiz-Pérez, MD; Salgado-Bustamante, M; Calderón-Aranda, E; Rodríguez-Pinal, CJ; Reynaga-Hernández, E; Corral-Fernández, NE; González-Amaro, R; Portales-Pérez, DP (2014) Mutation Research 761:27-34. HERO ID: 2279045

[Less] Humans may be exposed to arsenic (As) and fluoride (F) through water consumption. However, the interaction . . . [More] Humans may be exposed to arsenic (As) and fluoride (F) through water consumption. However, the interaction between these two elements and gene expression in apoptosis or inflammatory processes in children has not been thoroughly investigated. Herein, the expression of cIAP-1, XIAP, TNF-α, ENA-78, survivin, CD25, and CD40 was evaluated by RT-PCR. Additionally, the surface expression of CD25, CD40, and CD40L on peripheral blood mononuclear cells was analyzed by flow cytometry, and TNF-α was measured by Western blotting. This study examined 72 children aged 6-12 years who were chronically exposed to As (154.2μg/L) and F (5.3mg/L) in drinking water and in food cooked with the same water. The urine concentrations of As (6.9-122.4μg/L) were positively correlated with the urine concentrations of F (1.0-8.8mg/L) (r(2)=0.413, p<0.0001). The CD25 gene expression levels and urine concentrations of As and F were negatively correlated, though the CD40 expression levels were negatively correlated only with the As concentration. Age and height influenced the expression of cIAP-1, whereas XIAP expression was correlated only with age. Additionally, there was a lower percentage of CD25- and CD40-positive cells in the group of 6- to 8-year-old children exposed to the highest concentrations of both As and F when compared to the 9- to 12-year-old group (CD25: 0.7±0.8 vs. 1.1±0.9, p<0.0014; CD40: 16.0±7.0 vs. 21.8±5.8, p<0.0003). PHA-stimulated lymphocytes did not show any changes in the induction of CD25, CD69, or CD95. In summary, high concentrations of As and F alter the expression patterns of CD25 and CD40 at both the genetic and protein levels. These changes could decrease immune responses in children exposed to As and F.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from taiwan

Authors: Chou, WC; Chung, YT; Chen, HY; Wang, CJ; Ying, TH; Chuang, CY; Tseng, YC; Wang, SL (2014) PLoS ONE 9:e86398. HERO ID: 2279473

[Less] Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in . . . [More] Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001-2002 in Taiwan. We collected maternal urine samples during the 3(rd) trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N(7)-methylguanosine (N(7)-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N(7)-MeG (beta  = 0.35, p<0.001) and oxidative 8-oxodG (beta  = 0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta  = -0.23, p = 0.041). Maternal N(7)-MeG was also associated with a decreased 1-min Apgar score (beta  = -0.25, p = 0.042). Mutual adjustment for iAs and N(7)-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta  = -0.28, p = 0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N(7)-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Embryonic arsenic exposure reduces the number of muscle fibers in killifish (Fundulus heteroclitus)

Authors: D'Amico, AR; Gibson, AW; Bain, LJ (2014) Aquatic Toxicology 146:196-204. HERO ID: 2278549

[Less] Arsenic is a contaminant of drinking water and has been correlated with adverse developmental outcomes . . . [More] Arsenic is a contaminant of drinking water and has been correlated with adverse developmental outcomes such as low birth weight, reduced weight gain, and altered locomotor activity. Previous research has shown that killifish (Fundulus heteroclitus) exposed to high arsenic levels during embryogenesis had smaller muscle fiber diameters. The current study was designed to determine whether changes in muscle fibers persisted, were exacerbated, or resolved over time. Killifish embryos were exposed to 0-5 ppm arsenite and, upon hatching, were transferred into either clean water or continued receiving the same exposure to arsenic for up to 16 weeks. Arsenic significantly decreased the weight of both embryonic-only exposed juveniles and continuously exposed juveniles between 4 and 16 weeks of development at concentrations as low as 0.8 ppm. Although arsenite exposure increased the percentage of small diameter fibers during the early weeks, fiber diameters returned to control levels in the embryonic-only exposed fish. However, muscle fiber density was still reduced to 85.7%, 80.3%, and 73.8% of control for the 0.8, 2, and 5 ppm embryonic-only exposure groups, respectively, even after 16 weeks of development. These results indicate that while continuous exposure to arsenic may alter the size of muscle fibers, embryonic-only exposure to arsenic has lasting effects on the number of muscle fibers formed.