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  1. Arsenic Trioxide Injection

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    Arsenic trioxide is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there ... worsened following treatment with other types of chemotherapy. Arsenic trioxide is in a class of medications called ...

  2. Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro and in vivo.

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    Xiao-Yan Zhao

    Full Text Available BACKGROUND AND AIMS: Arsenic trioxide (As2O3, which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells. Isobolographic analysis was used to evaluate combination index values from cell viability data. The apoptosis and the cellular reactive oxygen species (ROS level were assessed by fluorescent microscopy and flow cytometry separately in vitro. The effect of As2O3, alone and in combination with resveratrol on Hela tumor growth in an orthotopic nude mouse model was also investigated. The tumor volume and the immunohistochemical analysis of CD31, CD34 and VEGF were determined. RESULTS: Resveratrol dramatically enhanced the anti-cancer effect induced by As2O3 in vitro. In addition, isobolographic analysis further demonstrated that As2O3 and resveratrol generated a synergistic action. More apoptosis and ROS generation were observed in the combination treatment group. Similar synergistic effects were found in nude mice in vivo. The combination of As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis in nude mice. CONCLUSIONS: Combining As2O3 with resveratrol would be a novel strategy to treat cancer in clinical practice.

  3. Synergistic inhibition of colon carcinoma cell growth by Hedgehog-Gli1 inhibitor arsenic trioxide and phosphoinositide 3-kinase inhibitor LY294002.

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    Cai, Xinyi; Yu, Kun; Zhang, Lijuan; Li, Yunfeng; Li, Qiang; Yang, Zhibin; Shen, Tao; Duan, Lincan; Xiong, Wei; Wang, Weiya

    2015-01-01

    The Hedgehog (Hh) signaling pathway not only plays important roles in embryogenesis and adult tissue homeostasis, but also in tumorigenesis. Aberrant Hh pathway activation has been reported in a variety of malignant tumors including colon carcinoma. Here, we sought to investigate the regulation of the Hh pathway transcription factor Gli1 by arsenic trioxide and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 in colon carcinoma cells. We transfected cells with siGli1 and observed a significant reduction of Gli1 expression in HCT116 and HT29 cells, which was confirmed by quantitative real-time polymerase chain reaction and Western blots. Knocking down endogenous Gli1 reduced colon carcinoma cell viability through inducing cell apoptosis. Similarly, knocking down Gli2 using short interfering RNA impaired colon carcinoma cell growth in vitro. To elucidate the regulation of Gli1 expression, we found that both Gli inhibitor arsenic trioxide and PI3K inhibitor LY294002 significantly reduced Gli1 protein expression and colon carcinoma cell proliferation. Arsenic trioxide treatment also reduced Gli1 downstream target gene expression, such as Bcl2 and CCND1. More importantly, the inhibition of Hedgehog-Gli1 by arsenic trioxide showed synergistic anticancer effect with the PI3K inhibitor LY294002 in colon carcinoma cells. Our findings suggest that the Hh pathway transcription factor Gli1 is involved in the regulation of colon carcinoma cell viability. Inhibition of Hedgehog-Gli1 expression by arsenic trioxide and PI3K inhibitor synergistically reduces colon cancer cell proliferation, indicating that they could be used as an effective anti-colon cancer combination therapy.

  4. Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

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    Zhang Yawei

    2009-08-01

    Full Text Available Abstract Background Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3 with cisplatin (DDP on A549 and H460 non-small cell lung cancer (NSCLC cells were explored. Methods A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT method, clonogenic assay, and flow cytometry (FCM. Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot. Results MTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The

  5. 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells.

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    Kuan-Lin Kuo

    Full Text Available 2-Methoxyestradiol (2-ME, an endogenous derivative of 17β-estradiol, has been reported to elicit antiproliferative responses in various tumors. In this study, we investigated the effects of 2-ME on cell viability, proliferation, cell cycle, and apoptosis in human urothelial carcinoma (UC cell lines. We used two high-grade human bladder UC cell lines (NTUB1 and T24. After treatment with 2-ME, the cell viability and apoptosis were measured by MTT assay and flow cytometry (fluorescence-activated cell sorting, with annexin V-FITC staining and propidium iodide (PI labeling. DNA fragmentation was analyzed by agarose gel electrophoresis. Flow cytometry with PI labeling was used for the cell cycle analyses. The protein levels of caspase activations, poly (ADP-ribose polymerase (PARP cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory molecules were measured by Western blot. The effects of the drug combinations were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9 activations can be observed with 2-ME-induced apoptosis. The decreased phospho-Bad (Ser136 and Ser155 and mitotic arrest of the cell cycle in the process of apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10 were activated. In combination with arsenic trioxide (As2O3, 2-ME elicited synergistic cytotoxicity (combination index <1 in UC cells. We concluded that 2-ME significantly induces apoptosis through decreased phospho-Bad and arrests bladder UC cells at the mitotic phase. The synergistic antitumor effect with As2O3 provides a novel implication in clinical treatment of UC.

  6. Synergistic effect of all-trans-retinoic acid and arsenic trioxide on growth inhibition and apoptosis in human hepatoma, breast cancer, and lung cancer cells in vitro

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    Le-Min Lin; Bao-Xin Li; Jian-Bing Xiao; Dan-Hua Lin; Bao-Feng Yang

    2005-01-01

    AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As2O3)-induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors.METHODS: Human hepatoma cell lines HepG2, Hep3B,human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As2O3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis were measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH)and glutathione-S-transferase (GST) activities were determined using commercial kits.RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1,and 10 μmol/L) could synergistically potentiate As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As2O3 or As2O3+ATRA, while AGZY-83-a with higher GSH or GST activities was less sensitive to As2O3or As2O3+ATRA. Treatment with 2 μmol/L As2O3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 μmol/L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As2O3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As2O3 and ATRA for 72 h as compared to As2O3 alone.CONCLUSION: ATRA can strongly potentiate As2O3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As2O3 or As2O3+ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergistically potentiates As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis.

  7. Synergistic effect of cell differential agent-Ⅱ and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells

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    Jian-Wei Liu; Yi Tang; Yan Shen; Xue-Yun Zhong

    2003-01-01

    AIM: To illustrate the possible role of cell differential agent-Ⅱ (CDA-Ⅱ) in the apoptosis of hepatoma cells induced byarsenic trioxide (As2O3).METHODS: Hepatoma cell lines BEL-7402 and HepG2 weretreated with As2O3 together with CDA-Ⅱ. Cell survivingfraction was determined by MTT assay; morphologicalchanges were observed by immunofluorescence staining ofHoechst 33 258; and cell cycle and the apoptosis index weredetermined by flow cytometry (FCM).RESULTS: Cytotoxity of CDA-Ⅱ was low. Nevertheless, CDA-Ⅱ could strongly potentiate arsenic trioxide-inducedapoptosis. At 1.0 g/L CDA-Ⅱ, IC50 of As2O3 in hepatoma celllines was reduced from 5.0 μmol/L to 1.0 μmol/L (P<0.01).The potentiation of apoptosis was dependent on the dosageof CDA-Ⅱ. FCM indicated that in hepatoma, cell growth wasinhibited by CDA-Ⅱ at lower concentrations (<2.0 g/L)primarily by arresting at S and G2 phase, and at higherconcentrations (>2.0 g/L) apoptotic cell and cell cyclearresting at G1 phaseincreased proportionally. Thecombination of two drugs led to much higher apoptotic rates,as compared with the either drug used alone.CONCLUSION: CDA-Ⅱ can strongly potentiate As2O3-induced apoptosis in hepatoma cells, and two drugs canproduce a significant synergic effect.

  8. Oral arsenic trioxide poisoning and secondary hazard from gastric content.

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    Kinoshita, Hidenori; Hirose, Yasuo; Tanaka, Toshiharu; Yamazaki, Yoshihiko

    2004-12-01

    In a suicide attempt, a 54-year-old man ingested arsenic trioxide. Gastric lavage was performed, but most of the poison remained as a mass in his stomach. A total gastrectomy was also performed to avoid intestinal perforation and arsenic poisoning. After the operation, he developed ventricular fibrillation. At one point, his circulation recovered spontaneously, but he later died from refractory circulatory failure. Many medical staff members were exposed to fumes from the patient's stomach. Some of the staff were diagnosed with corneal erosion or laryngitis. Because arsenic trioxide reacts with acid to produce arsine, the symptoms experienced by medical staff are directly attributable to arsine produced as a result of the reaction of arsenic trioxide with gastric acid. This case highlights the need for the introduction of protective measures to safeguard medical staff from exposure to arsine gas during the treatment of patients poisoned from ingested arsenic trioxide.

  9. Arsenic trioxide: an ancient drug revived

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    ZHOU Jin

    2012-01-01

    Objective To summarize the clinical applications of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL),as well as non-APL malignancies and to discuss the mechanisms and adverse effects involved in ATO administration.Data sources The data in this article were collected from PubMed and CHKD database with relevant English and Chinese articles published from 1957 to 2011,with key words including acute promyelocytic leukemia,arsenic trioxide,treatment,and mechanism.Study selection Articles including any information about ATO in the treatment of APL were selected.Results APL is a rare subtype of acute myeloid leukemia,with dismal prognosis under treatment with traditional chemotherapy.ATO impressively increases the complete remission rate and prolongs survival of patients with APL,with only mild and transient adverse effects.The advances in the understanding of multiple mechanisms involved in ATO treatment will benefit more cancers in future.Conclusion Deeper understanding of mechanisms involved in ATO treatment may provide rationales for future clinical applications in a number of human malignancies.Chin Med J 2012; 125( 19):3556-3560

  10. Arsenic trioxide negatively affects Echinococcus granulosus.

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    Wang, Bo; Jiang, Yufeng; Wang, Zhuo; Li, Fangfang; Xing, Guoqiang; Peng, Xinyu; Zhang, Shijie; Lv, Hailong

    2015-11-01

    Spillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate the in vitro efficacy of arsenic trioxide (ATO) against Echinococcus granulosus protoscolices. Protoscolices of E. granulosus were incubated in vitro with 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, the in vivo efficacy and possible side effects of ATO need to be explored.

  11. Arsenic trioxide: safety issues and their management

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    Wing-Yan AU; Yok-Lam KWONG

    2008-01-01

    Arsenic trioxide (As2O3) has been used medicinally for thousands of years.Its therapeutic use in leukaemia was described a century ago.Recent rekindling in the interest of As2O3 is due to its high efficacy in acute promyelocytic leukaemia (APL).As2O3 has also been tested clinically in other blood and solid cancers.Most studies have used intravenous As2O3,although an oral As2O3 is equally efficacious.Side effects of As2O3 are usually minor,including skin reactions,gastrointestinal upset,and hepatitis.These respond to symptomatic treatment or temporary drug cessation,and do not compromise subsequent treatment with As2O3.During induction therapy in APL,a leucocytosis may occasionally occur,which can be associated with fluid accumulation and pulmonary infiltration.The condition is similar to the APL differentiation syndrome during treatment with all-trans retinoic acid,and responds to cytoreductive treatment and corticosteroids.Intravenous As2O3 treatment leads to QT prolongation.In the presence of under-lying cardiopulmonary diseases or electrolyte disturbances,particularly hypokalaemia and hypomagnesaemia,serious arrhythmias may develop,with torsades du pointes reported in 1% of cases.This may be related to a dose-dependent arsenic-mediated inhibition of potassium ion channels that compro-mises cardiac repolarization.Because of slow intestinal absorption,oral-As2O3 gives a lower plasma arsenic concentration,which is associated with lesser QT prolongation and hence a more favorable cardiac safety profile.As2O3 does not appear to enter the central nervous system.However,if the blood brain barrier is breached,elemental arsenic may enter the cerebrospinal fluid.As2O3 is predomi-nantly excreted in the kidneys,and dose adjustment is required when renal func-tion is impaired.

  12. Inhibition factors of arsenic trioxide therapeutic effects in patients with acute promyelocytic leukemia

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    Sui Meijuan; Zhang Zhuo; Zhou Jin

    2014-01-01

    Objective To summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia,because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide.Data sources Most relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia","arsenic trioxide","thiol" or "methylation".In addition,a few older articles were also reviewed.Study selection Data and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed.We developed an overview of limitations associated with arsenic trioxide therapeutic effect.Results This review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees.First,with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second,arsenic methylation,stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third,gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.Conclusions The chief limitations are listed in the review.If we can exclude all of them,we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.

  13. Comparing two arsenic trioxide administration methods in APL therapy

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    周晋; 孟然; 杨宝峰

    2004-01-01

    @@ Arsenic trioxide (As2O3) was approved for the treatment of acute promyelocytic leukemia (APL) and was under investigation for other malignancies. However, some side effects occurred during APL treatment with routine As2O3 infusion. We tried a ' continuously slow As2O3 intravenous infusion ' method and assessed its effectiveness and security in APL treatment.

  14. Factors determining sensitivity and resistance of tumor cells to arsenic trioxide.

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    Serkan Sertel

    Full Text Available Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50 values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis. Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways significantly predicted cellular response to arsenic trioxide. Then, we analyzed whether classical drug resistance factors may also play a role for arsenic trioxide. Cell lines transfected with cDNAs for catalase, thioredoxin, or the anti-apoptotic bcl-2 gene were more resistant to arsenic trioxide than mock vector transfected cells. Multidrug-resistant cells overexpressing the MDR1, MRP1 or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed that response of tumor cells towards arsenic trioxide is multi-factorial.

  15. Hepatoprotective efficacy of curcumin against arsenic trioxide toxicity

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    VV Mathews; P Binu; MV Sauganth Paul; M Abhilash; Alex Manju; R Harikumaran Nair

    2012-01-01

    Objective: To evaluate the efficacy of curcumin in combating arsenic induced hepatic oxidative stress, histopathological changes and the hepatic arsenic accumulation in rat model. Methods:Oxidative stress was induced by oral administration 4 mg/kg b.wt of arsenic trioxide (As2O3,) for 45 days in experimental rats. The level of liver arsenic concentration, lipid peroxidation, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were determined in adult male Wistar rats. Hepatotoxicity was assessed by quantifying the aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phophatase (ALP). Hepatoprotective efficacy of curcumin (15 mg/kg b.wt) was evaluated by combination treatment with As2O3. Results: As2O3 administration leads to the generation of reactive oxygen species (ROS), arsenic accumulation, serum marker enzymes release and decrease in antioxidant enzymes in liver. Retention of arsenic in liver caused increased level of lipid peroxidation with a concomitant decline in the glutathione dependant antioxidant enzymes and antiperoxidative enzymes. Curcumin treatment protected the liver from arsenic induced deterioration of antioxidant levels as well as oxidative stress. And also a significant decrease in hepatic arsenic accumulation and serum marker enzymes was observed. Histopathological examination revealed a curative improvement in liver tissue. Conclusions:These findings lead to the conclusion that curcumin may have the potential to protect the liver from arsenic-induced toxic effects.

  16. Arsenic species excretion after dimercaptopropanesulfonic acid (DMPS) treatment of an acute arsenic trioxide poisoning

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    Heinrich-Ramm, R. [Ordinariat fuer Arbeitsmedizin der Universitaet Hamburg und Zentralinstitut fuer Arbeitsmedizin, Hamburg (Germany); Schaller, K.H.; Angerer, J. [Institut und Poliklinik fuer Arbeits-, Sozial- und Umweltmedizin der Universitaet Erlangen-Nuernberg, Schillerstr. 25, 91054 Erlangen (Germany); Horn, J. [Medizinische Klinik II, Toxikologische-internistische Intensivstation, Klinikum Nuernberg, Nuernberg (Germany)

    2003-02-01

    We studied the urinary excretion of the different arsenic species in urine samples from a young man who tried to commit suicide by ingesting about 0.6 g arsenic trioxide. He received immediate therapy with dimercaptopropanesulfonic acid (DMPS) after his delivery into the hospital. We assessed urinary arsenite (inorganic trivalent arsenic), arsenate (inorganic pentavalent arsenic), pentavalent dimethylarsinic acid (DMA) and pentavalent monomethylarsonic acid (MMA) in urine with ion-exchange chromatography and on-line hydride-technique atomic absorption spectrometry. The predominant amount of the excreted arsenic was unchanged trivalent inorganic arsenic (37.4%), followed by pentavalent inorganic arsenic (2.6%), MMA (2.1%), DMA (0.2%) and one unidentified arsenic species (0.7%, if calculated as DMA). In the first urine voiding in the clinic, the total arsenic concentration was 215 mg/l, which fell 1000-fold after 8 days of DMPS therapy. A most striking finding was the almost complete inhibition of the second methylation step in arsenic metabolism. As mechanisms for the reduced methylation efficiency, the saturation of the enzymatic process of arsenic methylation, the high dosage of antidote DMPS, which might inhibit the activity of the methyl transferases, and analytical reasons are discussed. The high dosage of DMPS is the most likely explanation. The patient left the hospital after a 12-day treatment with antidote. (orig.)

  17. 活细胞实时成像技术研究抗坏血酸(AA)协同砷剂抗人骨肉瘤MG-63的体外疗效%The synergistic effect of MG-63 cells treated with ascorbic acid (AA) and arsenic trioxide in vitro by using continuous live cell imaging and analysis platform (cell IQ)

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    黄晓春; 李泽兵; 陈增淦; 陈统一; 王玲燕

    2012-01-01

    Objective To study the synergistic effect of human osteosarcoma cell line MG-63 treated with ascorbic acid (AA) and arsenic trioxide (As2O3) in vitro. Methods We used continuous live cell imaging and analysis platform (cell IQ) to observe cell proliferation and morphologic change of MG-63 cells which were treated with AA (62. 5 /nmol/L) and As2O3 (1 jumol/L) alone or together . Results MG-63 cell proliferation was depressed observed when treated by A A (62. 5 fimol/L) and As2O3 (1 jumol/L) independently. The effect of AA (62. 5 μmol/L) plus As2O3 (1 /imol/L) was synergistic, which further inhibits MG-63 cell proliferation. Conclusions The treatment of AA combined with As2O3 can induce synergistic effect on the depression of MG-63 cell proliferation. This result provides a new pathway and basic reaserch data of treating osteosarcoma in clinical practice.%目的 研究抗坏血酸(ascorbic acid,AA)和三氧化二砷(arsenic trioxide,As2O3)抗人骨肉瘤细胞MG-63的体外疗效.方法 以MG-63细胞为体外模型,用62.5 μmol/L AA与1μmol/L As2O3单独或联合处理细胞,利用新型连续活细胞图像采集和分析平台(continuous live cell imaging and analysis platform,Cell IQ)实时观察细胞的生长情况和形态学的变化.结果 1 μmol/L As2O3和62.5 μmol/L AA单独处理都可抑制MG-63细胞的生长并诱导细胞死亡.1 μmol/L As2O3和62.5 μmol/L AA联合处理细胞较单独处理组细胞抑制效果更明显.结论 AA和AS2O3抗人骨肉瘤细胞Mg-63可起到协同作用,这一结果为临床治疗骨肉瘤提供了新的思路和实验依据.

  18. The effect of arsenic trioxide on human hepatoma cell line BEL-7402 culturedin vitro

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    You Lin Yang; Hong Yu Xu; Yuan Yuan Gao; Qiao Li Wu; Guang Qiang Gao

    2000-01-01

    AIM To study the effect of a wide range of concentration of arsenic trioxide on human hepatoma cell lineBEL-7402 and its mechanism.METHODS The BEL-7402 cells were treated with arsenic trioxide (a final concentration of 0.5, 1 and2 μmol/L, respectively) in various durations or for 4 successive days. The cell growth and proliferation wereobserved by cell counting and cell-growth curve. Morphologic changes were studied under electronmicroscopy. Flow cytometry was used to assay cell-DNA distribution and the protein expression of Bcl-2 andBax was detected by immunocytochemical method.RESULTS The cell growth was significantly inhibited by the different concentrations of arsenic trioxide asrevealed by cell counting and cell-growth curve. Arsenic trioxide treatment at 0.5, 1 and 2 μmol/L, resultedin a sub-G1 cell peak. The decreased G0/G1 phase cell and the increased percentage of S phase cell were observed by flow cytometer, suggesting that the inhibiting effect of arsernic trioxide on BEL-7402 cell lay inG0/G1 phase cell. Apoptotis-related morphology, such as intact cell membrane, nucleic condensation,apoptotic body formation, can be seen under the electron microscopy. High protein expression level of Bcl-2and Bax was detected in 1 and 2 μmol/L arsenic trioxide-treated cells, but that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/L resulted in higher expression level of Bcl-2 and lower expressionlevel of Bax compared with control (P1<0.01, P2<0.01).CONCLUSION Arsenic trioxide not only inhibited the proliferation but also induced apoptosis of humanhepatoma cell line BEL-7402. The induced-apoptosis effect of 1 and 2 μmol/L arsenic trioxide was relative tothe expression level of Bcl-2 and Bax.

  19. Cardiac conduction block at multiple levels caused by arsenic trioxide therapy.

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    Kathirgamanathan, Kala; Angaran, Paul; Lazo-Langner, Alejandro; Gula, Lorne J

    2013-01-01

    We present a rare case of a woman aged 62 years with refractory acute promyelocytic leukemia treated with arsenic trioxide leading to progressive, multilevel cardiac conduction block. After chelation treatment with dimercaprol, there was normalization of conduction.

  20. Parenthood in patients with acute promyelocytic leukemia after treatment with arsenic trioxide: a case series.

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    Gupta, Shilpa; Bagel, Bhausaheb; Gujral, Sumeet; Subramanian, P G; Khattry, Navin; Menon, Hari; Nair, Reena

    2012-11-01

    Arsenic trioxide, believed to be a carcinogen and a teratogen, has found its niche in the treatment of acute promyelocytic leukemia (APL). APL is a disease affecting young patients. Post-treatment fertility and outcome of pregnancy are always a concern in a disease with high cure rates. We report a case series of six patients who were treated successfully for APL with arsenic trioxide and who parented at least one healthy offspring after completing their treatment.

  1. Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report

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    Marcus Kuhn

    2016-05-01

    Full Text Available Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide.

  2. The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation

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    Zhi Xin WANG; Chun Sun JIANG; Lei LIU; Xiao Hui WANG; Hai Jing JIN; Qiao WU; Quan CHEN

    2005-01-01

    The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ. Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

  3. Mechanism of Arsenic Trioxide Inhibiting Angiogenesis in Multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to explore the molecular mechanism of arsenic trioxide treating multiple myeloma (MM) via inhibition of angiogenesis, the expression of brain derived neurotrophic factor (BD-NF) and its specific receptor TrkB in human MM cell line KM3 and endothelial cell line ECV304 was detected by Western blotting. The angiogenic activity was evaluated by wound migration assay and tubule formation assay in vitro. The results showed that BDNF was detected in the MM cells and TrkB in the endothelial cells. Furthermore, 100 ng/mL BDNF could significantly induced endo thelial cell tubule formation and wound migration. As2 O3 depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As2O3 inhibited BDNF-induced wound migration and capillary tube formation. It was concluded that BDNF is a novel angiogenic protein as well as VEGF and has a relation with the pathogenesis of MM. As2O3 interrupts a paracrine loop between MM cells and endothelial cells by down-regulating the TrkB expression in endothelial cells and inhibiting BDNF production in MM cells, finally resulting in inhibition of MM angiogenesis. This is probably one part of the mechanisms of the As2O3 treating MM via the inhibition of angiogenesis.

  4. ARSENIC TRIOXIDE DOWNREGULATES TELOMERASE ACTIVITY IN HL-60 CELLS

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    何冬梅; 张洹

    2002-01-01

    Objective: To evaluate whether arsenic trioxide (AS2O3) could downregulate human telomerase reverse transcriptase (hTERT) gene expression and telomerase activity during induction of apoptosis of HL-60 cells. Methods: Apoptosis was detected by morphological observation and flow cytomertric cell cycle analysis. The expression of hTERT at mRNA and protein levels was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence using fluoresce isothiocyanate (FITC) label, respectively. Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). Results: Treatment of 2 μmol/L at As2O3 could induce apoptosis of HL-60 cells. hTERT was decreased at both mRNA and protein levels during apoptosis of HL-60 cells. Telomerase activity of HL-60 cells was significantly inhibited. Conclusion:It is suggested that telomerase activity of HL-60 cells might be specifically inhibited by AS2O3 through the downregulation of hTERT gene expression.

  5. Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

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    Paul B. Tchounwou

    2006-06-01

    Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

  6. REPEATED ARSENIC TRIOXIDE INTRAVENOUS INFUSION CAUSES FOCAL BONE MARROW NECROSIS IN TWO ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    Jin Zhou; Ran Meng; Xin-hua Sui; Bao-feng Yang

    2004-01-01

    @@ Arsenic trioxide (As2O3) is an effective agent used in treatment of acute promyelocytic leukemia (APL). However,appearances of side effects using clinical therapeutic dosages of As2O3 occur during the initial or consolidated stage in APL therapy. We report two APL patients suffering focal bone marrow necrosis after discontinuous As2O3 treatment during consolidated stage.

  7. Arsenic trioxide induces Noxa-dependent apoptosis in rhabdomyosarcoma cells and synergizes with antimicrotubule drugs.

    Science.gov (United States)

    Meister, Michael Torsten; Boedicker, Cathinka; Graab, Ulrike; Hugle, Manuela; Hahn, Heidi; Klingebiel, Thomas; Fulda, Simone

    2016-10-28

    The prognosis of metastatic or relapsed rhabdomyosarcoma (RMS) is poor, highlighting the need of new treatment options. In the present study, we evaluated the in vitro efficacy of arsenic trioxide (ATO) in RMS, a FDA-approved drug used in pediatric leukemia. Here, we report that ATO exerts antitumor activity against RMS cells both as single agent and in combination with microtubule-targeting drugs. Monotherapy with ATO reduces cell viability, triggers apoptosis and suppresses clonogenic survival of RMS cells, at least in part, by transcriptional induction of the proapoptotic BH3-only protein Noxa. siRNA-mediated knockdown of Noxa significantly rescues ATO-mediated cell death, demonstrating that Noxa is required for cell death. Also, ATO suppresses endogenous Hedgehog (Hh) signaling, as it significantly reduces Gli1 transcriptional activity and expression levels of several Hh target genes. Furthermore, we identify synergistic induction of apoptosis by ATO together with several antimicrotubule agents including vincristine (VCR), vinblastine and eribulin. The addition of the broad-range caspase inhibitor zVAD.fmk or overexpression of the antiapoptotic protein Bcl-2 significantly reduce ATO/VCR-induced cell death, indicating that the ATO/VCR combination triggers caspase-dependent apoptosis via the mitochondrial pathway. In summary, ATO exerts antitumor activity against RMS, especially in combination with antimicrotubule drugs. These findings have important implications for the development of novel therapeutic strategies for RMS.

  8. Evidences of Protective Potentials of Microdoses of Ultra-High Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide

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    Pathikrit Banerjee

    2011-01-01

    Full Text Available The present study was undertaken to examine if microdoses of ultra-high diluted arsenic trioxide (a potentized homeopathic remedy, Arsenicum Album 200C, diluted 10-400 times have hepatoprotective potentials in mice subjected to repeated injections of arsenic trioxide. Arsenic intoxicated mice were divided into: (i those receiving Arsenicum Album-200C daily, (ii those receiving the same dose of diluted succussed alcohol (Alc 200C and (iii another group receiving neither drug nor succussed alcohol. Two other control groups were also maintained: one fed normal diet only and the other receiving normal diet and Alc-200C. Toxicity biomarkers like aspartate and alanine aminotransferases, glutathione reductase, catalase, succinate dehydrogenase, superoxide dismutase and reduced glutathione contents were periodically assayed keeping the observer “blinded”. Additionally, electron microscopic studies and gelatin zymography for matrix metalloproteinases of liver tissues were made at day 90 and 120. Blood glucose, hemoglobin, estradiol and testosterone contents were also studied. Compared to controls, Arsenicum Album-200C fed mice showed positive modulations of all parameters studied, thereby providing evidence of protective potentials of the homeopathic drug against chronic arsenic poisoning.

  9. Effect of TAK1 gene silencing on the apoptosis of Kasumi-1 cells induced by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    许锦霞

    2013-01-01

    Objective To study the effect of transforming growth factor-βactivated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As2O3) .Methods Acute myeloid

  10. EFFECT OF ARSENIC TRIOXIDE OR ATRA ON PRIMARY APL CELL OR HL-60 CELLS AND THEIR VALUE ANALYSIS IN HYPERLEUKOCYTOSIS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To detect the effect of arsenic trioxide or ATRA on APL cells or HL-60 cells and to investigate the mechanism of the hyperleukocytosis and detect the cross resistance between ATRA and arsenic trioxide. Methods: The number of promyelocytes or more matured granulocytes were counted by regular method, MTT test was used to measure the proliferation of HL-60 cells or APL cells, flow cytometry analysis to measure the apoptosis, NBT method to detect the differentiation of HL-60 cells or APL cells. Results: The proliferation of primary APL cells or HL-60 cells could be inhibited in vitro by either arsenic trioxide or ATRA, which could induce obvious apoptosis or obvious differentiation of primary APL cells or HL-60 cells. Inhibition of proliferation or apoptosis of ATRA resistant HL-60 cells were achieved by exposure toarsenic trioxide in vitro. On the other hand, the results of in vivo treatment showed that arsenic trioxide also induce of hyperleukocytosis. Conclusion: The results indicated that the hyperleukocytosis induced by ATRA is not contributed to the mechanism of more differentiation than apoptosis, there was not cross resistance between ATRA and arsenic trioxide.

  11. Role of Calcium Ion in Apoptosis of MD Cancer Cells Induced by Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jiuli; WANG Jintao; XU Shiwen

    2008-01-01

    In order to observe the role of calcium ion in apoptosis of MD cancer cells induced by arsenic trioxide, inhibition percentage was detected by MTT assay;morphology changes were examined by fluorescence microscope;apoptosis was examined by DNA Ladder;[Ca2+]i was investigated by spectrofluorimeter in vitro on MDCC-MSB1 cells. The results showed that As2O3 inhibited the proliferation of MDCC-MSB1 cells in concentration dependent manner (P<0.05 or P<0.01);typical apoptosis character was observed by fluorescence microscope;DNA Ladder was observed;the [Ca2+]i was elevated significantly after the treatment of As203 (P<0.05 or P<0.01) and showed a dose-dependent manner. It is concluded that the calcium may play an important role in apoptosis of MD cancer cells induced by arsenic trioxide.

  12. Effect of arsenic trioxide on cytokine expression by acute promyelocytic leukemia cells

    Institute of Scientific and Technical Information of China (English)

    姜国胜; 毕可红; 唐天华; 张玉昆; 任海全; 姜枫勤; 任青华; 真刚; 刘传芳; 彭军; 郭桂月; 刘秀兰; 田志刚

    2003-01-01

    Objective To detect the expression of cytokines by acute promyelocytic leukemia (APL) cells before and after exposure to arsenic trioxide. Methods Diagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized tubes,then primary APL cells were separated by traditional Ficoll-Hypaque density centrifugation and purified after adherence to plastic surfaces. IL-1β, IL-6, IL-8, TNFα and G-CSF levels in the leukemia cell culture supernatants were detected by ELISA. At the same time, nitro blue tetrazolium (NBT) reduction test was used to detect the differentiation of APL cells. Results After 96 hours exposure to arsenic trioxide, 10-6 mol/L in vitro or 10 mg/d in vivo, APL cells showed a significant increase of IL-1β(P<0.05) and G-CSF(P<0.05) production, and a significant decrease of IL-6 (P<0.05) and IL-8 (P<0.05). However, there was no obvious variation of TNFα when compared with APL cells without exposure to arsenic trioxide. On the other hand, the proliferation ratio of APL cells in vitro was statistically correlated to the IL-1β secretion ratio or G-CSF secretion ratio. The cell number ratio in patients with detectable IL-1β or G-CSF was higher than that without detectable IL-1β or G-CSF.Conclusion IL-1β and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to arsenic trioxide.

  13. Effects of arsenic trioxide on the methylation of TMS1 gene in K562 cells

    Institute of Scientific and Technical Information of China (English)

    李洪丽

    2014-01-01

    Objective To detect the methylation status of TMS1gene and its demethylation by arsenic trioxide(As2O2)in K562 cells.Methods K562 cells were treated with different concentrations of As2O2for 48 hours.Methylationspecific PCR(MSP)was used to determine the methylation status of TMS1.RT-PCR and Western blot were used to detect the levels of TMS1 mRNA and protein.

  14. Gene Expression Profile of Multiple Myeloma Cell Line Treated by Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    WANG Mengchang; LIU Shaanxi; LIU Pengbo

    2007-01-01

    cDNA microarray was used to compare the gone expression profiles of multiple myeloma cell line RPMI8226 24 h before and after treatment with arsenic trioxide. Two eDNA probes were prepared by mRNA reverse transcription of both arsenic trioxide-treated and untreated RPMI8226 cells. The probes were labeled with Cy3 and Cy5 fluorescence dyes separately, hybridized with cDNA microarray representing 4096 different human genes, and scanned for fluorescence intensity. The differences in gene expression were calculated on the basis of the ratios of signal intensity of treated and untreated samples. The up- and down-regulated genes were screened through the analysis of gene expression ratios. The results showed that 273 genes were differentially altered at mRNA level, 121 genes were up-regulated and 152 were down-regulated. It is concluded that the treatment with arsenic trioxide can induce a variety of gene changes in RPMI8226 cell line. Many genes may be involved in the pathogenesis of multiple myeloma. ALK-1 and TXNIP genes may play an impor- tant role in the apoptosis and partial differentiation of RPMI8226 cells.

  15. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

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    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

  16. Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice.

    Science.gov (United States)

    Kreppel, H; Paepcke, U; Thiermann, H; Szinicz, L; Reichl, F X; Singh, P K; Jones, M M

    1993-01-01

    The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Preparation of Arsenic Trioxide Albumin Microspheres and its Release Characteristics in Vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; ZENG Fuqing; GAO Xiang; XIE Shusheng; WEI Shuli

    2005-01-01

    Summary: Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.

  18. Evaluation of response to arsenic trioxide in patients with refractory multiple myeloma

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    Zohreh Sanaat

    2010-03-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Multiple myeloma is a plasma cell dyscrasia characterized by proliferation of plasma cells in bone marrow associated with the production of monoclonal immunoglobulins. In recent years, the use of arsenic trioxide, formerly approved for treatment of acute promyelocytic leukemia has been considered for refractory myeloma treatment. This study was designed and carried out to evaluate the efficacy and possible side effects of ATO on patients with refractory multiple myeloma."n"nMethods: This study carried out on myeloma patients whose diseases were at least refractory to two standard treatment regimens conducted in Ghazi Tabatabaei Hospital in Tabriz- Iran. Arsenic trioxide was administered as an intravenous infusion at a dose of 0.25 mg/kg/d for 5 d/week during the first two consecutive weeks of each 4-week cycle with two week rest. Patients who completed one 4-weak cycle were evaluated for response to treatment."n"nResults: Twelve patients with refractory disease to conventional treatment regimens received arsenic trioxide. The response to the treatment assessed based on the amount of serum proteins electrophoresis of the 10 patients. Stable disease observed in four patients (33%, progressive disease in five

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

    Science.gov (United States)

    Mathews, Varghese V; Paul, Mv Sauganth; Abhilash, M; Manju, Alex; Abhilash, S; Nair, R Harikumaran

    2014-10-01

    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.

  20. Inhibitory Effect of Arsenic Trioxide on Growth and Telomerase Activity of SMMC-7721 and BEL-7402 Hepatocarcinoma Cells and Determination of their GSH Content

    Institute of Scientific and Technical Information of China (English)

    Weiwei Ren; Hong Li; Yuan Zhang

    2006-01-01

    OBJECTIVE To explore the inhibitory effect of arsenic trioxide on growth and telomerase activity of BEL-7402 and SMMC-7721 hepatocarcinoma cells, and to measure their GSH level.METHODS Cell culture and trypan blue exclusion were used to examine the inhibitory effect of arsenic trioxide on BEL-7402 and SMMC-7721 hepatocarcinoma lines. A GSH kit and telomerase kit were used to mearsure the GSH content in cells and telomerase activity.RESULTS The growth of BEL-7402 cells was significantly inhibited at a level of 0.50 μmol/L of arsenic trioxide by 24 h. The inhibitory effect increased with time and concetration of arsenic trioxide. The telomerase activity of BEL-7402 cells was also significantly inhibited at a level of 0.50 μmol/L of arsenic trioxide by 24 h, after which the inhibitory effect increased with time. On the other hand, at 24 h of incubation a level of 2.00 μmol/L of arsenic trioxide was required to significantly inhibit growth of SMMC-7721 cells, and only after 48 h with 2.00 μmol/L of arsenic trioxide did telomerase activity significantly decline. The GSH content of the BEL-7402 and SMMC-7721 cells was 18.7±1.4 and 50.8±5.2 nmol/mg protein respectively, a significant difference.CONCLUSION Different concentrations of arsenic trioxide are required to inhibit growth and telomerase activity of SMMC-7721 and BEL-7402cells. Perhaps BEL-7402 cells are more sensitive to arsenic trioxide because of their low level of GSH content, which results in a low capacity for oxidation-reduction and poorer detoxification mechanisms in BEL-7402 cells.

  1. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  2. Evaluation of chronic toxicity of Kushta Sammulfar (calx of Arsenic trioxide

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    Athar Parvez Ansari

    2013-06-01

    Full Text Available Sammulfar (arsenic trioxide is a notorious poison and has extensively been studied for its toxicity. It is in use for various purposes for centuries and is used even today as a therapeutic agent in the form of kushta (calx in traditional systems of medicine, particularly Unani medicine, but without apparent safety data. The present study, therefore, was conducted to produce data for prolong use of calx of arsenic trioxide. The calx (test drug was prepared by the method described in National Formulary of Unani Medicine. The study was carried in healthy Wistar rats of either sex; weighing 150-250 g; 2-3 months of age, in a dose dependent manner, following the methods of Gupta et al. (2002, Ghosh (2008 and Klaassan (2008. The animals were divided into four groups of 10 animals each. Group I served as control, where as group II, III and IV were used for three dose levels of the test drug i.e. low (8.75 mg–1 kg, medium (17.50 mg–1 kg and higher (26.25 mg–1 kg. Standard parameters usually applied for chronic toxicity studies were considered. The study revealed dose dependent toxicity. Usual signs of chronic toxicity were observed during the study. Low dose of Kushta Sammulfar (KSF did not produce remarkable toxic effects. Mild to moderate toxicity was seen in KSF-II and KSF-III.

  3. Rationale and efficacy of proteasome inhibitor combined with arsenic trioxide in the treatment of acute promyelocytic leukemia

    Science.gov (United States)

    Ganesan, S; Alex, A A; Chendamarai, E; Balasundaram, N; Palani, H K; David, S; Kulkarni, U; Aiyaz, M; Mugasimangalam, R; Korula, A; Abraham, A; Srivastava, A; Padua, R A; Chomienne, C; George, B; Balasubramanian, P; Mathews, V

    2016-01-01

    Arsenic trioxide (ATO) mediates PML-RARA (promyelocytic leukemia–retinoic acid receptor-α) oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment-mediated drug resistance (EMDR) to ATO in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines. The mechanism of this synergy involved downregulation of the nuclear factor-κB pathway, increase in unfolded protein response (UPR) and an increase in reactive oxygen species generation in the malignant cell. We also noted that PML-RARA oncoprotein is effectively cleared with this combination in spite of proteasome inhibition by bortezomib, and that this clearance is mediated through a p62-dependent autophagy pathway. We further demonstrated that proteasome inhibition along with ATO had an additive effect in inducing autophagy. The beneficial effect of this combination was further validated in an animal model and in an on-going clinical trial. This study raises the potential of a non-myelotoxic proteasome inhibitor replacing anthracyclines in the management of high-risk and relapsed APL. PMID:27560113

  4. The effect of arsenic trioxide on QT interval prolongation during APL therapy

    Institute of Scientific and Technical Information of China (English)

    周晋; 孟然; 李晓霞; 吕成芳; 范圣瑾; 杨宝峰

    2003-01-01

    Objective To investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3), and the relationship between QT and serum arsenic concentration.Methods Blood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As2O3 injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett ' s formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group1 (Hb≥90 g/L), and Group 2 (60 g/L≤Hb<90 g/L). QTc and QTd of these patients were also manually measured.Results All QT intervals of APL patients treated with As2O3 injection were prolonged [32.2 ms (27, 41 ms); P 0.05]. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent.Conclusions As2O3 can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As2O3 has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.

  5. 三氧化二砷与癌细胞凋亡%Arsenic Trioxide and Carcinoma Cell Apoptosis

    Institute of Scientific and Technical Information of China (English)

    王建华; 徐小英; 王远亮

    2002-01-01

      Arsenic trioxide, an inorganic compound of trivalent arsenic, is highly poisonous after acute exposure and carcinogenic following chronic exposure. Although arsenicals have long been used therapeutically, they have aroused increasing interest recently by the discovery that arsenic trioxide can induce apoptosis in the APL cell and other cancer cells. The article demonstrates the relative concepts of apoptosis and summarizes the effect of arsenic trioxide to the carcinoma, its possible principle included.%  三氧化二砷是一种剧毒化合物,长期接触会致癌。作为药物,砷化合物已有很久历史,近期由于其可诱导急性早幼粒白血病细胞和其它癌细胞凋亡而备受关注。文章叙述了细胞凋亡的相关概念,总结了三氧化二砷近年来对癌细胞的凋亡作用以及其可能的机理。

  6. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Chia-Wen [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan (China); Yao, Ju-Hsien [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); Chang, Shih-Yu [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Lee, Pei-Chih [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); Lee, Te-Chang, E-mail: bmtcl@ibms.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China)

    2011-11-15

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  7. Grape seed and skin extract protects against arsenic trioxide induced oxidative stress in rat heart.

    Science.gov (United States)

    Sfaxi, Ichraf; Charradi, Kamel; Limam, Ferid; El May, Michèle Veronique; Aouani, Ezzedine

    2015-07-29

    Arsenic is a metalloid found in water, soil, and air from natural and anthropogenic sources, and is commonly found in inorganic as well as organic forms. The clinical use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) is limited by its cardiotoxic side effects. Grape seed and skin extract (GSSE) is a polyphenolic mixture with antioxidant properties. This study aimed to evaluate the protective effect of GSSE on arsenic-induced cardiac oxidative stress and injury. Animals exposed to 2.5 mg/kg As2O3 for 21 days exhibited a relevant increase in heart lipoperoxidation, protein carbonylation, and inflammation, as well as a drop in the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, As2O3 disturbed heart lipidemia and lipase activity, transition metals distribution and the associated enzymes, intracellular mediators such as calcium and the associated calpain activity, as well as myocardial architecture. Treatment with 4 g/kg GSSE protected against most of the deleterious effects provoked by As2O3. Our data suggest that GSSE has the potential to protect against As2O3-induced cardiotoxicity.

  8. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  9. The Protective Role of Resveratrol against Arsenic Trioxide-Induced Cardiotoxicity

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    Weiqian Zhang

    2013-01-01

    Full Text Available Arsenic trioxide (As2O3 shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL. Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3 in heart via nuclear factor erythroid 2-related factor 2 (Nrf2 and heme oxygenase-1 (HO-1 is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3 on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3 might provide a novel therapeutic strategy for APL.

  10. Inhibition of interleukin-13 gene expression in T cells through GATA-3 pathway by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    YAO Xin; HE Hai-yan; YANG Yan; DAI Shan-lin; SUN Pei-li; YIN Kai-sheng; HUANG Mao

    2008-01-01

    @@ Arsenic trioxide (AT) has a long history of use in both traditional Chinese medicine and in modern medicine in asthma therapy.Recently,Yin et al1 found that AT even at small doses reduced the airway inflammation of sensitized guinea pigs.However the mechanism underlying this is still largely unknown.Interleukin 13 (IL-13),as one of the important TH2 cytokines,plays an important role in asthma pathogenesis through promoting eosinophilic inflammation,mucus secretion and airway hyperresponsiveness.2 To further explore the molecular anti-inflammatory basis of AT,we employed Hut-78 cells,a human T cell line,with activation via CD3/CD28 receptors to mimick in vivo co-stimulation to investigate the effect of AT on IL-13 transcription.

  11. Erythema multiforme due to arsenic trioxide in a case of acute promyelocytic leukemia: A diagnostic challenge

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    Girish V Badarkhe

    2016-01-01

    Full Text Available Erythema multiforme (EM is an acute, self-limited, Type IV hypersensitivity reactions associated with infections and drugs. In this case of acute promyelocytic leukemia, EM diagnosed during the induction phase was mistakenly attributed to vancomycin used to treat febrile neutropenia during that period. However, the occurrence of the lesions of EM again during the consolidation phase with arsenic trioxide (ATO lead to a re-evaluation of the patient and both the Naranjo and World Health Organization-Uppsala Monitoring Centre scale showed the causality association as “probable.” The rash responded to topical corticosteroids and antihistamines. This rare event of EM being caused by ATO may be attributed to the genetic variation of methyl conjugation in the individual which had triggered the response, and the altered metabolic byproducts acted as a hapten in the subsequent keratinocyte necrosis.

  12. STUDY ON THE RELATIONSHIP OF ARSENIC TRIOXIDE-INDUCED BIOLOGICAL EFFECTS AND DEGRADATIONOF PML PROTEINS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To understand whether arsenic trioxide (As2O3)-induced biological effects are associated with degradation of PML proteins. Methods Acute promyelocytic leukemia (APL) cell line NB4, acute T-lymphocytic leukemia cell line Jurkat, acute myeloid leukemia cell line U937, and chronic myelocytic leukemia blast crisis cell line K562 were used as in vitro models. In different cell lines, the As2O3-induced bio- logical effects were determined by cell growth, cell viability, cell morphology, and flow cytometry assay on sub- G1 cell content. The alteration of PML proteins was analyzed by immunofluorescence. Results In terms of growth inhibition and apoptosis induction, 1.0μmol/L As2O3 had different effects on different cell lines. However, degradation of PML proteins occurred in all the cell lines with As2O3 treatment. Conclusion As2O3-induced biological effects may be independent of PML protein degradation.

  13. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

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    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  14. Enhancement of arsenic trioxide-mediated changes in human induced pluripotent stem cells (IPS).

    Science.gov (United States)

    Graham, Barbara; Stevens, Jacqueline; Wells, Phatia; Sims, Jennifer; Rogers, Christian; Leggett, Sophia S; Ekunwe, Stephen; Ndebele, Kenneth

    2014-07-22

    Induced pluripotent stem cells (IPS) are an artificially derived type of pluripotent stem cell, showing many of the same characteristics as natural pluripotent stem cells. IPS are a hopeful therapeutic model; however there is a critical need to determine their response to environmental toxins. Effects of arsenic on cells have been studied extensively; however, its effect on IPS is yet to be elucidated. Arsenic trioxide (ATO) has been shown to inhibit cell proliferation, induce apoptosis and genotoxicity in many cells. Based on ATOs action in other cells, we hypothesize that it will induce alterations in morphology, inhibit cell viability and induce a genotoxic effect on IPS. Cells were treated for 24 hours with ATO (0-9 µg/mL). Cell morphology, viability and DNA damage were documented. Results indicated sufficient changes in morphology of cell colonies mainly in cell ability to maintain grouping and ability to remain adherent. Cell viability decreased in a dose dependent manner. There were significant increases in tail length and moment as well as destruction of intact DNA as concentration increased. Exposure to ATO resulted in a reproducible dose dependent sequence of events marked by changes in morphology, decrease of cell viability, and induction of genotoxicity in IPS.

  15. The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

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    Liu Qian

    2010-08-01

    Full Text Available Abstract Background Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out. Methods Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI50 data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP database. Selected biomarkers were tested in vitro for the ability to influence tumor susceptibility to arsenic trioxide. Results A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2 with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down. Conclusions In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in

  16. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

  17. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    Science.gov (United States)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  18. Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

    Science.gov (United States)

    Varghese, Mathews V; Abhilash, M; Paul, M V Sauganth; Alex, Manju; Nair, R Harikumaran

    2017-04-01

    Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.

  19. Phytopathological and nutraceutical evaluation of cauliflower plants treated with high dilutions of arsenic trioxide

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    Lucietta Betti

    2012-09-01

    Full Text Available Introduction: This research aimed at verifying the effects of highly diluted (HD treatments on cauliflower (Brassica oleracea L. plants both healthy and inoculated by the fungus Alternaria brassicicola, causing the dark leaf spot disease. In vitro spore germination assays (A, growth chamber experiments (B and field trials (C were performed. Material and Methods: (A: spore suspensions were prepared in HD treatments and their inhibiting effect on germination was recorded microscopically after incubation at 25°C for 5 h. (B: the same treatments were tested in plants artificially inoculated with the fungus. The infection level on leaves was blindly evaluated by a previously defined infection scale. (C: the field was divided into plots according to a complete randomized block design. In the first trial (i, plants were artificially inoculated and weekly treated; the infection level was evaluated on cauliflower heads. The second trial (ii was performed on the same field with the aim to induce a natural infection, mediated by infected crop residues. Measurement endpoints concerned the evaluation of some physiological parameters along with the glucosinolate content on cauliflower heads. Results: (A: arsenic trioxide (As 35x and 35x diluted 1:5000 and Cuprum 5x induced highly significant inhibition of germination rate (-60% vs. control. (B: As 35x and Cu 3 g/l induced a significant decrease of mean infection level (-50%. (C: in (i, a significant reduction of disease symptoms on heads was recorded for As 35x and Cu 3 g/l (-45%. In (ii natural fungal infection did not occur due to dry weather conditions; physiological and nutraceutical analyses of healthy heads demonstrated that As 35x induced a significant increase of both head size and glucosinolate content. Discussion: Some evidences on the efficacy of arsenic, at different decimal and centesimal HD, in fungal and viral disease control were previously reported [1]. In the present study the

  20. STUDY ON EFFECTS OF ARSENIC TRIOXIDE ON GASTRIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    顾琴龙; 朱正纲; 洪鹤群; 刘炳亚; 尹浩然; 林言箴; 李宁丽

    2002-01-01

    Objective To evaluate the effects of arsenic trioxide (As2O3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As2O3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As2O3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As2O3 at a concentration of 0.5μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As2O3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As2O3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.

  1. Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis

    Science.gov (United States)

    Zhang, Yong; Wu, Xianxian; Li, Yang; Zhang, Haiying; Li, Zhange; Zhang, Ying; Zhang, Longyin; Ju, Jiaming; Liu, Xin; Chen, Xiaohui; Glybochko, Peter V.; Nikolenko, Vladimir; Kopylov, Philipp; Xu, Chaoqian; Yang, Baofeng

    2016-01-01

    Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity. PMID:27671604

  2. Arsenic Trioxide Inhibits Proliferation in K562 Cells by Changing Cell Cycle and Survivin Expression

    Institute of Scientific and Technical Information of China (English)

    伍晓菲; 陈智超; 刘仲萍; 周浩; 游泳; 黎纬明; 邹萍

    2004-01-01

    To study the mechanisms involved in the inhibition of chronic myeloid leukemic cells (K562) proliferation induced by arsenic trioxide (As2O3) and to explore the potential role of Survivin, an inhibitor of apoptosis protein, in the regulation of As2O3 induced cell apoptosis, K562 cells were cultured with As2O3 of different concentrations. Cells were collected for proliferation analysis by MTT assay. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry.Expression of Survivin protein and mRNA were detected by flow cytometry and RT-PCR, respectively. Our results showed that As2O3 (2-10 μmol/L) inhibited K562 cells growth effectively, but it did not induce cells apoptosis significantly. The percentage of K562 cells at G2/M phase increased in proportion to As2O3 concentrations, and the expression of Survivin mRNA and content of Survivin protein was up-regulated accordingly. It is concluded that As2 O3 inhibited K562 cells growth by inducing cell cycle arrest mainly at G2/M phase. Over-expression of Survivin gene and protein might be one of the possible mechanisms contributing to K562 cells' resistance to As2O3-induced apoptosis.

  3. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells.

    Science.gov (United States)

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer.

  4. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

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    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  5. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors

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    Robert J. Griffin

    2000-01-01

    Full Text Available Arsenic trioxide, As2O3 (ATO, has been found to be an effective chemotherapy drug for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSall tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5-42.5°C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFa are noticeably increased in tumors 2–6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

  6. Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells.

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    Li-Li Song

    Full Text Available Despite considerable efficacy of arsenic trioxide (As2O3 in acute promyelocytic leukemia (APL treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML, are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment.

  7. Targeting hedgehog signalling by arsenic trioxide reduces cell growth and induces apoptosis in rhabdomyosarcoma.

    Science.gov (United States)

    Boehme, Karen A; Zaborski, Julian J; Riester, Rosa; Schweiss, Sabrina K; Hopp, Ulrike; Traub, Frank; Kluba, Torsten; Handgretinger, Rupert; Schleicher, Sabine B

    2016-02-01

    Rhabdomyosarcomas (RMS) are soft tissue tumours treated with a combination of surgery and chemotherapy. However, mortality rates remain high in case of recurrences and metastatic disease due to drug resistance and failure to undergo apoptosis. Therefore, innovative approaches targeting specific signalling pathways are urgently needed. We analysed the impact of different hedgehog (Hh) pathway inhibitors on growth and survival of six RMS cell lines using MTS assay, colony formation assay, 3D spheroid cultures, flow cytometry and western blotting. Especially the glioma-associated oncogene family (GLI) inhibitor arsenic trioxide (ATO) effectively reduced viability as well as clonal growth and induced cell death in RMS cell lines of embryonal, alveolar and sclerosing, spindle cell subtype, whereas normal skeletal muscle cells were hardly compromised by ATO. Combination of ATO with itraconazole potentiated the reduction of colony formation and spheroid size. These results show that ATO is a promising substance for treatment of relapsed and refractory RMS by directly targeting GLI transcription factors. The combination with itraconazole or other chemotherapeutic drugs has the opportunity to enforce the treatment efficiency of resistant and recurrent RMS.

  8. Various tolerances to arsenic trioxide between human cortical neurons and leukemic cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; MENG Ran; SUI Xinhua; LI Wenbin; YANG Baofeng

    2006-01-01

    Arsenic trioxide (As2O3) is very effective for treatment of acute promyelocytic leukaemia (APL) but little can pass through the blood-brain-barrier (BBB),which limits its use in the prevention and treatment of central nervous system leukaemia (CNSL). Before creating a non-invasive method to help As2O3 's access, the safe and effective therapeutic concentration of As2O3 in the CNS ought to be known. The changes of apoptosis biomarkers, [Ca2+]i and PKC activity of both leukaemia cells and human cortical neurons, were monitored before and after being treated with As2O3 in vitro with laser confocal microscopy and Western blot. NSE concentration, the neuron invasive biomarker, was monitored by enzyme immunoassay (NSE-EIA). This study revealed that cortical neuron was more tolerable to As2O3 compared to NB4. 1.0 μmol / L As2O3 showed little influence on cortical neuron but effectively promoted apoptosis and induced differentiation of NB4.

  9. Morphine Attenuated the Cytotoxicity Induced by Arsenic Trioxide in H9c2 Cardiomyocytes.

    Science.gov (United States)

    Amini-Khoei, Hossein; Hosseini, Mir-Jamal; Momeny, Majid; Rahimi-Balaei, Maryam; Amiri, Shayan; Haj-Mirzaian, Arya; Khedri, Mostafa; Jahanabadi, Samane; Mohammadi-Asl, Ali; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

    2016-09-01

    Arsenic trioxide (ATO) is an efficient drug for the treatment of the patients with acute promyelocytic leukemia (APL). Inhibition of proliferation as well as apoptosis, attenuation of migration, and induction of differentiation in tumor cells are the main mechanisms through which ATO acts against APL. Despite advantages of ATO in treatment of some malignancies, certain harmful side effects, such as cardiotoxicity, have been reported. It has been well documented that morphine has antioxidant, anti-apoptotic, and cytoprotective properties and is able to attenuate cytotoxicity. Therefore, in this study, we aimed to investigate the protective effects of morphine against ATO toxicity in H9c2 myocytes using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, caspase 3 activity, nuclear factor kappa B (NF-κB) phosphorylation assay, and expression of apoptotic markers. Our results showed that morphine (1 μM) attenuated cytotoxicity induced by ATO in H9c2 cells. Results of this study suggest that morphine may have protective properties in management of cardiac toxicity in patients who receive ATO as an anti-cancer treatment.

  10. Differential binding of monomethylarsonous acid compared to arsenite and arsenic trioxide with zinc finger peptides and proteins.

    Science.gov (United States)

    Zhou, Xixi; Sun, Xi; Mobarak, Charlotte; Gandolfi, A Jay; Burchiel, Scott W; Hudson, Laurie G; Liu, Ke Jian

    2014-04-21

    Arsenic is an environmental toxin that enhances the carcinogenic effect of DNA-damaging agents, such as ultraviolet radiation and benzo[a]pyrene. Interaction with zinc finger proteins has been shown to be an important molecular mechanism for arsenic toxicity and cocarcinogenesis. Arsenicals such as arsenite, arsenic trioxide (ATO), and monomethylarsonous acid (MMA(III)) have been reported to interact with cysteine residues of zinc finger domains, but little is known about potential differences in their selectivity of interaction. Herein we analyzed the interaction of arsenite, MMA(III), and ATO with C2H2, C3H1, and C4 configurations of zinc fingers using UV-vis, cobalt, fluorescence, and mass spectrometry. We observed that arsenite and ATO both selectively bound to C3H1 and C4 zinc fingers, while MMA(III) interacted with all three configurations of zinc finger peptides. Structurally and functionally, arsenite and ATO caused conformational changes and zinc loss on C3H1 and C4 zinc finger peptide and protein, respectively, whereas MMA(III) changed conformation and displaced zinc on all three types of zinc fingers. The differential selectivity was also demonstrated in zinc finger proteins isolated from cells treated with these arsenicals. Our results show that trivalent inorganic arsenic compounds, arsenite and ATO, have the same selectivity and behavior when interacting with zinc finger proteins, while methylation removes the selectivity. These findings provide insights on the molecular mechanisms underlying the differential effects of inorganic versus methylated arsenicals, as well as the role of in vivo arsenic methylation in arsenic toxicity and carcinogenesis.

  11. Role of Low Dosage Arsenic Trioxide on Pulmonary Dendritic Cells in Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    周林福; 殷凯生; 周智敏

    2003-01-01

    Objective: To investigate the distribution and recruitment of pulmonary dendritic cells (DCs) and the influence of low dosage arsenic trioxide (As2O3) on them in the airway of asthmatic mice. Methods: Thirty BALB/c mice were randomly divided into 3 groups: the control group, the asthmatic group and the As2O3 treated group. The mice asthmatic model was induced via sensitizing with peritoneal injection of ovalbumin (OVA) for two times and then provocated with aerosol inhalation of OVA for a week. The treated group was peritoneally injected with 0.2 ml solution of As2O3 (4mg/kg) 0.5h after each provocation. The immunohistochemistry and computerised image analysis were applied to detect quantitatively the DCs in the lung and airway of mice. Results: All intraepithelial nonlymphoid dendritic cells-145 (NLDC-145) throughout the respiratory tree in the mice of the control group formed a network with the density of DCs varying from (575±54) cells/mm2 epithelial surface in the large airway, to (68±12) cells/mm2 epithelial surface in the small airway. The distribution of airway NLDC-145+ in the asthmatic group was similar to that in the control group, but its density was significantly upregulated (P<0.01). The distribution of airway NLDC-145 in the treated group was similar to that in the asthmatic group, only its density was significantly downregulated (P<0.01). Conclusion: There is an integral network of NLDC-145+ throughout the respiratory tree. To downregulate the density but not change the distribution of pulmonary DCs could be an important therapeutic mechanism of low dosage As2O3 in treating asthma.

  12. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0 μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells,but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  13. Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.

    Science.gov (United States)

    Feng, Tao; Qiao, Guanglei; Feng, Li; Qi, Weixiang; Huang, Yujing; Yao, Yang; Shen, Zan

    2014-12-01

    Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. Numerous patients are unable to be cured due to the development of resistance of the osteosarcoma cells to chemotherapeutic drugs. Therefore, reversion of drug resistance is urgently required for the treatment of osteosarcoma. Arsenic trioxide (As2O3) is an active ingredient in Traditional Chinese Medicine, but the therapeutic potential of As2O3 in osteosarcoma remains largely unexplored. The current study investigated the effects of As2O3 on MG63 osteosarcoma cells using a cell proliferation assay, flow cytometric analysis of the cell cycle and cell apoptosis, reverse transcription polymerase chain reaction to detect stathmin mRNA expression levels and western blot analysis to detect the stathmin protein expression levels. As2O3 and doxorubicin (ADM) combination treatment markedly inhibited cell proliferation in ADM-resistant MG63 (MG63/dox) osteosarcoma cells, clearly induced G2/M phase cell cycle arrest and increased the number of apoptotic MG63/dox cells. Furthermore, stathmin expression was found to be downregulated in MG63/dox cells and was sensitive to ADM treatment. Additional investigation revealed that the downregulation of stathmin expression in MG63/dox cells by stathmin small interfering RNA significantly enhanced the reversion of ADM resistance in MG63/dox by As2O3. The data indicated that As2O3 reversed ADM resistance in MG63/dox cells through downregulation of stathmin and may be a potential drug for the treatment of ADM-resistant osteosarcoma.

  14. LEUKOCYTOSIS AND RETINOIC ACID SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ARSENIC TRIOXIDE

    Institute of Scientific and Technical Information of China (English)

    Bo Jin; Ke-zuo Hou; Yun-peng Liu; Ping Yu

    2006-01-01

    Objective To study the incidence of leukocytosis and retinoic acid (RA) syndrome in newly diagnosed and relapsed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO).Methods Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms: fever,dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray.Results Twenty-three (77%) patients achieved complete remission, mean time to remission was 37.1 days. Leukocytosis was observed in 14 (47%) patients, mean time to leukocytosis was 12.7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 × 109/L, which was higher than that for patients who did not develop leukocytosis (2.6×109/L, z=-2.635, P=0.008). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9(30%) patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6×109/L, which was higher than that for patients who did not develop RA syndrome (2.6 × 109/L, z=-1.909, P=0.046). No patient died of RA syndrome.Conclusion Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively,and there is distinct link between leukocytosis and RA syndrome.

  15. Proteomic analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in leukemia K562 cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zi-hui; YU Ding; CHEN Yan; HAO Jian-zhong

    2005-01-01

    Background Arsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics. Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells. Conclusions: As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.

  16. Studies on arsenic trioxide induced mice melanoma Cloundman S91 cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ruzhi Zhang; Wenyuan Zhu; Chen Wang

    2005-01-01

    Objective: To invesfgate the effects of various concentrations As2O3 on malignant melanoma. Methods: The viability of Cloundman melanoma S91 cells treated with As2O3 was measured by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] assay. The apoptosis was determined by transferase-mediated dUTP nick end labeling (TUNEL) detection, and the morphology of apoptotic cells was observed through transmission electron microscopy (TEM). The cells growth phase were analyzed by flow cytometry (FCM). Results: A time-and dose-dependent decrease in cell viability was induced in S91 cells after treatment with As2Os at the concentration of 1-5 μmol/L respectively. The TUNEL indices were 0.033 ± 0.018, 0.062 ± 0.012, 0.102 ± 0.016, 0.132 ± 0.031,and 0.162 ± 0.027 respectively, which were much higher compared with the control group (0.017 ± 0.004, P < 0.01). The flow cytometry showed that hypodiploid peak after treatment with 3 μmol/L and 5 μmol/L of As2O3 for 48 h were 9.99% and 17.59% respectively,which increased significantly compared with the control cells (3.05% P < 0.01, ). The apoptotic morphology observed by transmission electron microscope showed the chromatin became condensed and attached to the inner surface of nuclear membrane. Conclusion: Arsenic trioxide can induce melanoma Cloundman S91 cell apoptosis at the concentration of 1-5 μmol/L, which will provide enhanced benefit in melanoma therapy.

  17. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment

    Science.gov (United States)

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-01

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity

  18. ETME, a novel β-elemene derivative, synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway

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    Zhiying Yu

    2014-12-01

    Full Text Available Arsenic trioxide (ATO has been identified as an effective treatment for acute promyelocytic leukemia (APL but is much less effective against solid tumors such as hepatocellular carcinoma (HCC. In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yltryptophan methyl ester (ETME. Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.

  19. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

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    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  20. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  1. Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhong; JI Hong Tan; Xiao Hua Jiang; Min Min Qiao; Yu Xin Wu; Shi Hu Jiang; ShuiPing Tu

    2000-01-01

    AIM To study the effects of arsenic trioxide and HCPT on different degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28)with respect to both cytotoxicity and induction of apoptosis in vitro. ~ODS The cytotoxicity of As2O3 and HCPT on gastric cancer cells was determined by MTTassay. Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy. Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As2O3 were investigated by TUNEL method and flow cytometry. RESULTS As2O3 and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC50 of As2O3 on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8. 91 μmol/L, 10. 57 μmol/L, and 11.65 μmol/L, respectively. The IC50 of HCPT on MKN-28, SGC-7901, and MKN-45 were 9. 35 rg/L, 10. 21 rg/L, and 12. 63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, including cell shrinkage, nuclear condensation,and formation of apoptotic bodies. A typical subdiploid peak before G0/G1 phase was observed by flow cytometry. The apoptotic rates of SGC7901, MKN-45, and MKN-28 were 13. 84%, 22.52%, and 9. 68%, respectively after 48 h exposure to 10 μmol/L As2O3. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30. 26%, respectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7% - 15% as assessed by TUNEL method. The effect of As2O3 on SGC-7901 showed remarkable cell cycle specificity, which induced cell death in G1 phase, and blocked G2/M phase. HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G1 phase and arrest of proliferation at S phase. CONCLUSION AS2O3 and HCPT exhibit significant

  2. Activity of Nanobins Loaded with Cisplatin and Arsenic Trioxide in Primary and Metastatic Breast Cancer

    Science.gov (United States)

    Swindell, Elden Peter, III

    Despite recent advances in breast cancer screening and detection, the disease is still a leading cause of death for women of all ages. Young, African-American women are disproportionally affected with a type of breast cancer, triple-negative breast cancer, which is particularly difficult to treat and has the worst prognosis of any breast cancer subtype. These tumors often spread to the lungs, liver, bones and brains of patients, which is ultimately fatal. This dissertation presents results from a series of in vivo and in vitro experiments that investigate the clinical utility of a novel nanoparticulate formulation of cisplatin and arsenic trioxide, NB(Pt,As) for treating primary and metastatic triple-negative breast cancer. These nanobins consist of a solid, crystalline metal nanoparticle surrounded by a lipid bilayer with 80-90 nm diameter. This drug payload is extremely stable, and so NB(Pt,As) is extremely well tolerated in mice. Furthermore, NB(Pt,As) is effective in two different mouse models of breast cancer, one of primary tumor growth an another of lung metastases. A discovery presented here, that thiol containing compounds are required for drug release, may explain these seemingly incongruous results. The large amount of intracellular thiol can trigger drug release, while the low concentration of free thiols in blood is insufficient to cause drug release. To improve the treatment of brain tumors with this unique drug, we added transferrin to the surface of the nanobin using copper-catalyzed "click" chemistry, which preserves protein activity. The addition of transferrin to the nanobins enables 10 fold greater uptake in the brains of mice treated with the transferrin-targeted nanobins Tf-NB(Pt,A) compared to NB(Pt,As). By penetrating the blood brain barrier, the Tf-NB(Pt,As) was able to reduce breast cancer metastases in the brains of mice, whereas NB(Pt,As) had no effect. Taken together, these results demonstrate the intricate balance of drug release

  3. Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide.

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    Irene Amigo-Jiménez

    Full Text Available BACKGROUND: Matrix metalloproteinase-9 (MMP-9 contributes to chronic lymphocytic leukemia (CLL pathology by regulating cell migration and preventing spontaneous apoptosis. It is not known if MMP-9 is involved in CLL cell response to chemotherapy and we address this in the present study, using arsenic trioxide (ATO and fludarabine as examples of cytotoxic drugs. METHODS: We used primary cells from the peripheral blood of CLL patients and MEC-1 cells stably transfected with an empty vector or a vector containing MMP-9. The effect of ATO and fludarabine was determined by flow cytometry and by the MTT assay. Expression of mRNA was measured by RT-PCR and qPCR. Secreted and cell-bound MMP-9 was analyzed by gelatin zymography and flow cytometry, respectively. Protein expression was analyzed by Western blotting and immunoprecipitation. Statistical analyses were performed using the two-tailed Student's t-test. RESULTS: In response to ATO or fludarabine, CLL cells transcriptionally upregulated MMP-9, preceding the onset of apoptosis. Upregulated MMP-9 primarily localized to the membrane of early apoptotic cells and blocking apoptosis with Z-VAD prevented MMP-9 upregulation, thus linking MMP-9 to the apoptotic process. Culturing CLL cells on MMP-9 or stromal cells induced drug resistance, which was overcome by anti-MMP-9 antibodies. Accordingly, MMP-9-MEC-1 transfectants showed higher viability upon drug treatment than Mock-MEC-1 cells, and this effect was blocked by silencing MMP-9 with specific siRNAs. Following drug exposure, expression of anti-apoptotic proteins (Mcl-1, Bcl-xL, Bcl-2 and the Mcl-1/Bim, Mcl-1/Noxa, Bcl-2/Bax ratios were higher in MMP-9-cells than in Mock-cells. Similar results were obtained upon culturing primary CLL cells on MMP-9. CONCLUSIONS: Our study describes for the first time that MMP-9 induces drug resistance by modulating proteins of the Bcl-2 family and upregulating the corresponding anti-apoptotic/pro-apoptotic ratios. This

  4. Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

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    C.W. Du

    2006-05-01

    Full Text Available Nasopharyngeal carcinoma (NPC is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1. Arsenic trioxide (As2O3 has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5/mL were cultured with or without 3 µM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i the colony formation inhibition rate (75.41 ± 3.9% in HNE1-LMP1 cells vs 37.89 ± 4.9% in HNE1 cells, the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9%, the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1%, and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27% were all significantly different between the two cell lines (P < 0.01. ii LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

  5. Effect of arsenic trioxide on rat hepatocarcinoma and its renal cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Shao-Shan Wang; Ti Zhang; Xi-Lu Wang; Li Hong; Qing-Hui Qi

    2003-01-01

    AIM: To study the effect of arsenic trioxide (As2O3) on rat experimental hepatocarcinoma and its renal cytotoxicity.METHODS: The hepatocarcinoma model was established by diethaylnitrosamine perfusion in stomach of 120 Wistar rats, and the treatment began at the end of 20 weeks.Before the treatment, the rat models were randomly divided into 5 groups. In the treatment groups, three doses of As2O3 were injected into rat abdominal cavity, the total time of drug administration was 4 weeks. Cisplatin control or the blank group was injected into abdominal cavity with equal amount of cisplatin or saline at the same time,respectively. On the 7th, 14th and 28th day after the treatment, the hepatocarcinoma nodules were obtained and the morphologic changes of hepatocarcinoma cells were observed under light and electron microscopes;Immunohistochemistry (S-P methods) was employed to detect the expression of bcl-2, bax and PCNA in hepatocarcinoma tissues; flow cytometry (TUNEL assay)was used to detect the apoptosis of liver cancer cells and the change of cytokinetics. On the 28th day, the kidneys were obtained and their histologic changes were observed under light microscope, and immunohistochemistry (SP stain) was also employed to detect the expression of bcl-2and PCNA. Cisplatin and saline solution were used as the control.RESULTS: As2O3 could induce the apoptosis of rat liver cancer cells and exhibited typical morphologic changes.The incidence of apoptosis of hapatocarcinoma cells was elevated (P=0.001). The elevation was the most higher in the group of middle-dose of As2O3 (1 mg.kg-1), significantly higher than that of the other arsenic groups and the controls (P=0.001). Large dose of As2O3 (5 mg.kg-1) was able to arise the incidence of apoptosis, but also produced a large amount of necrosis and inflammatory reaction. Middle dose of As2O3 dramatically increased the cell number in G2/M phase (P=0.0001), and apoptosis happened apparently.The expression of bcl-2 and bax was

  6. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH SINGLE-AGENT ARSENIC TRIOXIDE

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    Biju George

    2011-01-01

    Full Text Available

    It is well recognized that arsenic trioxide (ATO is an efficacious agent for the treatment of acute promyelocytic leukemia (APL. Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority. ATO is probably the most effective single agent in the treatment of APL and there have been very few reports of primary resistance. It has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. However, its role in newly diagnosed APL remains controversial. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s is likely to lead to more rationale use of this agent or its derivatives either alone or in combination with other drugs. There is limited data on the kinetics of leukemia clearance and normal haematopoietic recovery after the administration of single agent ATO for the treatment of APL, preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short and long term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long term arsenic exposure in the environment. With the therapeutic doses and schedules of administration of ATO in the treatment of malignancies the overall toxicity profile has been favorable. In a resource constrained environments the use of a single agent ATO based regimen is a realistic and acceptable option to treat almost all patients. In the developed world it has the potential in combination with other

  7. Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jin; WANG Wei; WEI Qing-fang; FENG Tie-ming; TAN Li-jun; YANG Bao-feng

    2007-01-01

    @@ Arsenic trioxide (ATO) can induce cellular apoptosis and inhibit the activities of multiple myeloma (MM)cells in vitro,1 but how it works is not very clear. Recent studies showed that ATO worked on the voltagedependent potassium channel and L-type calcium channel in myocardial cells,2-5 but the effect of ATO on ion channels of tumor cells was rarely reported. As the potassium channel plays an important role in controlling cell proliferation,6 we studied the effects of ATO on the voltage-dependent potassium current (Ikv) of the voltage-dependent potassium channel in an MM cell line,and probed into the relationship between changes of the Ikv caused by ATO and cell proliferation.

  8. Refractory acute promyelocytic leukemia successfully treated with combination therapy of arsenic trioxide and tamibarotene: A case report

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    Minoru Kojima

    2016-01-01

    Full Text Available A 40-year-old male developed refractory acute promyelocytic leukemia (APL after various treatments including all-trans retinoic acid, tamibarotene, arsenic trioxide (As2O3, conventional chemotherapy, and autologous peripheral blood stem cell transplantation. We attempted to use both tamibarotene and As2O3 as a combination therapy, and he achieved molecular complete remission. Grade 2 prolongation of the QTc interval on the electrocardiogram was observed during the therapy. The combination therapy of As2O3 and tamibarotene may be effective and tolerable for treating refractory APL cases who have no treatment options, even when they have previously been treated with tamibarotene and As2O3 as a single agent.

  9. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

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    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  10. Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    于鼎; 王子慧; 朱立元; 邱殷庆

    2003-01-01

    Objective To investigate arsenic trioxide (As2O3)-induced apoptosis and the effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Methods HepG2 cells were cultured in MEM medium and treated with 0.5, 2, 5 and 10 μmol/L As2O3 for either 24 h or 96 h at each concentration. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladders were used to detect apoptosis. Confocal microscopy and Western blotting were used to observe the expression of PML. Results The growth rates of HepG2 cells were slower in the As2O3 treated than the untreated control group. DNA ladder and TUNEL positive apoptotic cells could be detected in As2O3 treated groups. The expression of PML decreased in HepG2 cells with 2 μmol/L As2O3 treatment. Confocal images demonstrated that the expression of PML protein in HepG2 cell nuclei decreased after treatment with 2 μmol/L As2O3, and micropunctates characteristic of PML protein in HepG2 cell nuclei disappeared after treatment with 5 μmol/L As2O3.Conclusions Our results show that arsenic trioxide can significantly inhibit the growth of HepG2 cells in vitro. As2O3 induces apoptosis in HepG2 tumor cells in a time and concentration dependent manner. As2O3 may degrade the PML protein in HepG2 cell nuclei. The decreased expression of PML in As2O3 treated tumor cells is most likely to be caused by apoptosis. Nuclear matrix associated protein PML could be the target of As2O3 therapy.

  11. Synergistic effects of the combination of oxalate and ascorbate on arsenic extraction from contaminated soils.

    Science.gov (United States)

    Lee, Jae-Cheol; Kim, Eun Jung; Baek, Kitae

    2017-02-01

    Arsenic is often associated with iron oxides in soils due to its high affinity with iron oxides and the abundance of iron oxides in the environment. Dissolution of iron oxides can subsequently release arsenic associated with them into the environment, which results in the increase of arsenic mobility in the soil environment. In this study, arsenic extraction from soils via the dissolution of iron oxides was investigated using oxalate, ascorbate, and their combination in order to effectively remediate arsenic-contaminated soils. Oxalate mainly extracted iron from soils via a ligand-promoted reaction, while ascorbate extracted iron mainly via a reductive reaction. Arsenic extractions from soils by oxalate and ascorbate were shown to behave similarly to iron extractions, indicating the concurrent release of arsenic adsorbed on iron oxides upon the dissolution of iron oxides. The combination of oxalate and ascorbate greatly increased arsenic extraction, indicating the synergistic effects of the combination of oxalate and ascorbate on iron and arsenic extraction from soils. Oxalate and ascorbate are naturally-occurring organic reagents that have chelating and reducing capacity. Therefore, the use of oxalate and ascorbate is environmentally friendly and effective for the remediation of arsenic-contaminated soils.

  12. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma.

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    Shannon M Matulis

    Full Text Available Arsenic trioxide (ATO has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2-3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

  13. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions.

    Science.gov (United States)

    Srivastava, Ritesh K; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A; Harrod, Kevin S; Deshane, Jessy S; Athar, Mohammad

    2016-10-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4(+/+) wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4(+/-) heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca(++) homeostasis. ATO induces Ca(++)-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca(++) homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic.

  14. Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

    Institute of Scientific and Technical Information of China (English)

    邓友平; 林晨; 郑杰; 梁萧; 陈洁平; 付明; 肖培根; 吴旻

    1999-01-01

    It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As2O3 on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrephoresis and in situ cell death detection (TUNEL), it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted, However, it was found that As2O3 at a high concentratio

  15. Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Huanchen Cheng; Lin Qiu; Hao Zhang; Mei Cheng; Wei Li; Xuefei Zhao; Keyu Liu; Lei Lei; Jun Ma

    2011-01-01

    Arsenic trioxide (ATO) as an anti-tumor drug could induce differentiation and apoptosis in tumor cells.Mesenchymal stem cells (MSCs) play important roles in the hematogenesis of bone marrow. Many reports have shown that the disorder of MSC adipogenic and osteogenic differentiation occurs in some diseases. However,reports about the effects of ATO on MSCs are limited. In this study, we found that 1μM ATO promoted MSC senescence mainly through p21, although it had no effect on apoptosis at this dose. Furthermore, ATO promoted adipogenic differentiation, but inhibited osteogenic differentiation in MSCs. Our study also showed that CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor gamma PPARγ might be involved in the regulation of adipogenic and osteogenic differentiation induced by ATO. Our results indicated that ATO may exert an anti-tumor effect by influencing bone marrow micro-environment. Moreover, it may regulate the adipogenic and osteogenic differentiation of MSCs.

  16. Impact of Arsenic Trioxide on LS-174T Cell Growth in vitro and the Activity of Telomerase

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The therapeutic action of arsenic trioxide( As2O3 ) on solid tumors has aroused widespread interest among scholars. To study the impact of As2 O3 on human colorectal carcinoma cells( LS-174T cell) and the activity of telomerase,the methods of PCR-ELISA, flow cytometry (FCM) and MTT assay in vitro were utilized. The results show that ( 1 ) with an increase in the concentration of As2 O3, the ratio of living the cells to dead cells decreases significantly,and the IC50 value is 5. 23 μg/mL; (2) the cells of the experimental groups can endure a series of morphological changes similar to the features of apoptosis; (3) the apoptotic curves of FCM pictures appear after 24 h, and the cells show the apoptosis in a time-dependent manner; (4) As2O3 can inhibit the activity of telomerase of the cell extraction obviously in a concentration-dependent and time-dependent manner after 24 h. It can be concluded from the experiment results in vitro that As2O3 can induce the apoptosis of LS-174T cells and inhibit the telomerase activity. Therefore, it has been proposed, for the first time, that these two factors( the apoptosis of LS-174T cells and the inhibition to the telomerase activity) are important causes of the LS-174T cell death caused by As2O3.

  17. Sulindac and its metabolites: sulindac sulfide and sulindac sulfone enhance cytotoxic effects of arsenic trioxide on leukemic cell lines.

    Science.gov (United States)

    Stępnik, Maciej; Ferlińska, Magdalena; Smok-Pieniążek, Anna; Gradecka-Meesters, Dobrosława; Arkusz, Joanna; Stańczyk, Małgorzata

    2011-08-01

    The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200 μM) with SS being the most cytotoxic (72 h WST-1 reduction test). The cytotoxicity of ATO was enhanced by combination with sulindacs. The combination of ATO (1 μM) with SS or SF at concentrations over 50 μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48 h to the combinations showed smaller decrease in viability. Measurements of Jurkat, HL-60 and K562 cells exposed to ATO (1 μM) and sulindacs (100 μM or 200 μM for K562 cells) indicated apoptosis as the main cell death mechanism. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.

  18. Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts

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    Wen-Xiao Xu

    2015-11-01

    Full Text Available Background/Aims: Promyelocytic leukemia (PML protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα to contribute to the initiation of acute promyelocytic leukemia (APL. Arsenic trioxide (ATO upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Methods: Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. Results: ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conclusion: These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts.

  19. Prognostic factors of patients with newly diagnosed acute promyelocytic leukemia treated with arsenic trioxide-based frontline therapy.

    Science.gov (United States)

    Lou, Yinjun; Ma, Yafang; Suo, Shanshan; Ni, Wanmao; Wang, Yungui; Pan, Hanzhang; Tong, Hongyan; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; Huang, Jian; Yu, Wenjuan; Wei, Juyin; Mao, Liping; Jin, Jie

    2015-09-01

    Prognostic factors for patients with acute promyelocytic leukemia (APL) treated in the context of arsenic trioxide (ATO)-based frontline regimes have not been established clearly. We retrospectively analyzed the clinical features, immunophenotypes, Fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), and outcomes of 184 consecutive newly diagnosed APL patients treated by intravenous ATO-based therapy. The median age was 40 years (14-77 years). The early death rate was 4.9% (9/184 patients). With a median follow-up time of 36 months (9-74 months), the 3-year relapse-free survival (RFS) and overall survival (OS) were 93.3% and 92.2%, respectively. Interestingly, there was no meaningful association between 3-year RFS and initial white blood cell count, FLT3-ITD status, or type of PML-RARA isoforms. In multivariable analysis, the CD56 expression was the only independent risk factor in terms of RFS (hazard ratio, 4.70; P=0.005). These results suggested that ATO-based therapy may ameliorate the unfavorable influence of previously known high-risk features; moreover, CD56 expression remains to be a potentially unfavorable prognostic factor in APL patients.

  20. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Science.gov (United States)

    Wang, Min; Sun, Guibo; Wu, Ping; Chen, Rongchang; Yao, Fan; Qin, Meng; Luo, Yun; Sun, Hong; Zhang, Qiang; Dong, Xi; Sun, Xiaobo

    2013-01-01

    Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects. PMID:23662152

  1. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Min Wang

    2013-01-01

    Full Text Available Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2 cells and human cervical cancer (HeLa cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects.

  2. Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHENGYuwu; DUCaiwen; LIDerui; LINYingcheng; WUMingyao

    2004-01-01

    To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1 cells were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As203 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As203 treatment group when compared with control group. Conclusion: As203 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  3. 三氧化二砷的代谢途径及毒理机制综述%Toxicity Mechanisms and Metabolic Pathways of Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    牛一民; 樱井徹郎; 孙晖; 王喜军

    2011-01-01

    Arsenic trioxide is well known as a deadly poison. However, arsenous acid injection, which is originated from white arsenic in traditional Chinese medicine (TCM), has great efficacy in the treatment of acute promyeloeytic leukemia (APL). This medication is still accompanied with some severe adverse drug reactions (ADR). This paper tried to discuss metabolic pathways, as well as acute and chronic mechanisms of arsenic trioxide. The hypothetic ADB mechanism of arsenous acid injection was proposed to provide basis for new drug discovery in order to eliminate ADR.%三氧化二砷作为剧毒药广为人知,传统中药称其为"砒霜",而从中药砒霜中诞生的亚砷酸注射液其治疗急性早幼粒细胞白血病的疗效又为世人所瞩目,但仍伴随不同程度的不良反应.本文主要介绍了三氧化二砷的代谢途径及急慢性毒性机制,提出亚砷酸注射液不良反应的机制假设,为研究开发消除不良反应的药物提供依据.

  4. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.

    Science.gov (United States)

    Abaza, Yasmin; Kantarjian, Hagop; Garcia-Manero, Guillermo; Estey, Elihu; Borthakur, Gautam; Jabbour, Elias; Faderl, Stefan; O'Brien, Susan; Wierda, William; Pierce, Sherry; Brandt, Mark; McCue, Deborah; Luthra, Rajyalakshmi; Patel, Keyur; Kornblau, Steven; Kadia, Tapan; Daver, Naval; DiNardo, Courtney; Jain, Nitin; Verstovsek, Srdan; Ferrajoli, Alessandra; Andreeff, Michael; Konopleva, Marina; Estrov, Zeev; Foudray, Maria; McCue, David; Cortes, Jorge; Ravandi, Farhad

    2017-03-09

    The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m(2) daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m(2) on day 1) added to high-risk patients (white blood cell count, >10 × 10(9)/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

  5. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats

    Institute of Scientific and Technical Information of China (English)

    XUE Dong-bo; ZHANG Wei-hui; YUN Xiao-guang; SONG Chun; ZHENG Biao; SHI Xing-ye; WANG Hai-yang

    2007-01-01

    Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide (As2O3) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis.Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258+PI or Annexin V+PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α (TNF-α) mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with As2O3. The levels of lactate dehydrogenase and amylase release were markedly decreased in As2O3 treated group.Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As2O3 treated group were significantly lower than in the untreated group.Conclusions As2O3 can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.

  6. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell lines

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide(As2O3) on the mitochondrial DNA(mtDNA) of acute promyelocytic leukemia(APL) cells.The NB4 cell line was treated with 2.0 μmol/L As2O3 in vitro,and the primary APL cells were treated with 2.0 μmol/L As2O3 in vitro and 0.16 mg kg-1 d-1 As2O3 in vivo.The mitochondrial DNA of all the cells above was amplified by PCR,directly sequenced and analyzed by Sequence Navigatore and Factura software.The apoptosis rates were assayed by flow cytometry.Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use,but the mutation spots were remarkably increased after As2O3 treatment,which was positively correlated to the rates of cellular apoptosis,the correlation coefficient:rNB4-As2O3=0.973818,and rAPL-As2O3=0.934703.The mutation types include transition,transversion,codon insertion or deletion,and the mutation spots in all samples were not constant and regular.It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo.Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

  7. Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance.

    Directory of Open Access Journals (Sweden)

    Ezhilarasi Chendamarai

    Full Text Available There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL in comparison with newly diagnosed cases (NAPL. We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022. The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38% of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92, cell survival (n=50, immune regulation (n=74 and stem cell regulation (n=51. Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001 in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.

  8. The present treatment and mechanism progress of arsenic trioxide in hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Zhi-Gang Zhao

    2016-01-01

    Arsenic trioide (ATO) is a kind of highly toxic substances and the main effective components of arsenic. ATO has been used medicinally for over 2400 years. Recent years, many studies have found that ATO has a significant efficacy on the acute promyelocytic leukemia (APL). To further explore the latest findings of research on the treatment of hematologic malignanies of ATO, this paper reviewed the development history of ATO, and summarized its mechanisms and clinical application in the treatment of hematologic malignancies. In addition, we want to provide new ideas for researches on the treatment of cancer of ATO.%三氧化二砷(ATO)是一种剧毒物质,又是中药砒霜的主要成分,人类用它作为药物治疗疾病已有2400多年的历史。近年来发现ATO对急性早幼粒细胞性白血病(APL)具有显著的疗效。为进一步了解ATO治疗血液系统恶性肿瘤作用的研究近况,本文回顾ATO的研发历史,并总结其在治疗血液恶性肿瘤中的作用机制及临床应用,以期为ATO治疗肿瘤方面的研究提供新的思路。

  9. Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival.

    Science.gov (United States)

    Chen, Yan; Gu, Ling; Zhou, Chenyan; Wu, Xueqiang; Gao, Ju; Li, Qiang; Zhu, Yiping; Jia, Cangsong; Ma, Zhigui

    2010-05-01

    The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

  10. The current research of arsenic trioxide in the treatment of acute promyelocytic leukemia%三氧化二砷治疗急性早幼粒细胞白血病的研究现状

    Institute of Scientific and Technical Information of China (English)

    郭晶杰

    2013-01-01

    Arsenic trioxide( ATO )is presently one of the most effective single agent in the treatment of a-cute promyelocytic leukemia( APL ). ATO impressivly increases the complete remission rate and prolongs survival of patients with APL with only mild and transient adverse effects. The mechanisms of ATO mainly include promoting differentiation,inducing apoptosis,accumulating reactive oxygen species,and eliminating leukemic - initiating cells. And synergistic actions in introduction of apoptosis and differentiation between ATO and all - trans - retino-ic acid have been shown. In relapsed APL, ATO - based salvage therapy has been able to induce long - lasting remissions and possible cure in 50% -81% of patients. The high anti - leukemic efficacy and the favorable toxicity profile of ATO were also shown in newly diagnosed APL,because high remission and cure rates could even be induced by ATO alone. Experimental research and clinical studies have established ATO as an important candidate for the further improvement of APL therapy.%三氧化二砷(Arsenic trioxide,ATO)是目前单药治疗急性早幼粒细胞白血病(Acute promyelocytic leukemia,APL)最有效的药物之一,可明显提高APL的完全缓解率,延长患者的生存期,且不良反应较轻.ATO的作用机制主要为诱导APL细胞分化与凋亡、促使细胞内活性氧水平升高和去除白血病启动细胞等,并且在诱导分化和凋亡方面与全反式维甲酸起协同作用.对于复发性APL,以ATO为基础的挽救疗法能够诱导APL长期缓解并且50%~81%的患者可能治愈.在初发APL中,ATO表现出抗白血病的高效性和低毒性,使APL获得较高的缓解率和治愈率.因此,对ATO进行深入的基础及临床研究将为进一步优化ATO对APL的治疗提供重要的参考.

  11. Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Yang, Daqian; Lv, Zhanjun; Zhang, Haili; Liu, Biying; Jiang, Huijie; Tan, Xiao; Lu, Jingjing; Baiyun, Ruiqi; Zhang, Zhigang

    2017-03-01

    Arsenic trioxide (As2O3) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As2O3-treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As2O3-induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As2O3-induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As2O3 (3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As2O3-induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-κB level and upregulated expression of proteins reduced by As2O3 including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Krüppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2-associated X protein levels regulated by As2O3. However, neither allicin nor As2O3 affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As2O3-induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As2O3-induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure.

  12. Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of neurosphere derived from glioblastoma by downregulation of Notch pathway.

    Science.gov (United States)

    Wu, Jianing; Ji, Zhiyong; Liu, Huailei; Liu, Yaohua; Han, Dayong; Shi, Chen; Shi, Changbin; Wang, Chunlei; Yang, Guang; Chen, Xiaofeng; Shen, Chen; Li, Huadong; Bi, Yunke; Zhang, Dongzhi; Zhao, Shiguang

    2013-06-20

    Notch signaling has been demonstrated to have a central role in cancer stem-like cells (CSLCs) in glioblastoma multiforme (GBM). We have recently demonstrated the inhibitory effect of arsenic trioxide (ATO) on CSLCs in glioblastoma cell lines. In this study we used neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after ATO treatment. Our results provided strong evidence that ATO depleted CSLCs in GBM, and inhibited neurosphere recovery and secondary neurosphere formation. ATO inhibited the phosphorylation and activation of AKT and STAT3 through Notch signaling blockade. These data show that the ATO is a promising new approach to decrease glioblastoma proliferation and recurrence by downregulation of Notch pathway.

  13. Anti-hepatoma effect of arsenic trioxide on experimental liver cancer induced by 2-acetamidofiuorene in rats

    Institute of Scientific and Technical Information of China (English)

    Bing Tan; Jie-Fei Huang; Qun Wei; Hong Zhang; Run-Zhou Ni

    2005-01-01

    AIM: To study the anti-hepatoma efficiency of arsenic trioxide (As2O3) in the treatment of experimental rat hepatocellular carcinoma (HCC) induced by 2-acetamidofluorene (2-FAA)and to elucidate the possible mechanisms.METHODS: SD rats (2 mo old) had been fed with 2-FAA for 8 wk to induce HCC, and then they were treated with As2O3 or matrine. On d 29, the rats were killed and the liver was weighed and liver tumors were counted. The histological changes of liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Immunohistochemistry (two-step method) was used to observe the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD) on consecutive sections. The pathological parameters were also analyzed, the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),total bilirubin (TBi), and direct bilirubin (DBi).RESULTS: The number of liver tumors decreasedsignificantly in groups treated with As2O3, especially in medium-dose (1 mg/kg) group (t = 2.80, P<0.01). As2O3 caused HCC cell death via apoptosis; necrosis was seen and apoptosis was common when the dose was 1 mg/kg.Proliferation index decreased sharply in medium-dose (1 mg/kg) group (7.87±4.11 vs 24.46±6.49, t = 2087,P<0.01), but not in 0.2 mg/kg group. However, S-phase fraction decreased dramatically in both groups, it reached the bottom level only when the dose was 1 mg/kg compared with control (0.40±0.13 vs 3.01±0.51, t = 2.97, P<0.01),and it was obviously accompanied with accumulation of cells in G0/G± (G0/G1 restriction). The expressions of VEGF and MVD in medium-dose (1 mg/kg) group were significantly lower than normal saline group (0.63±0.74 vs 2.44±0.88, P<0.05; 15.75±3.99 vs47.44±13.41, t= 2.80,P<0.01). Compared with normal saline group, mediumand low-dose groups As2O3 and matrine lowered the levels of ALT in serum (61.46±9.46, 63.75±20.40, 61.18±13.00 vs 108.98±29.86, t= 2

  14. Dithiothreitol enhanced arsenic-trioxide-induced cell apoptosis in cultured oral cancer cells via mitochondrial dysfunction and endoplasmic reticulum stress.

    Science.gov (United States)

    Tsai, Chia-Wen; Yang, Mei-Due; Hsia, Te-Chun; Chang, Wen-Shin; Hsu, Chin-Mu; Hsieh, Yi-Hsien; Chung, Jing-Gung; Bau, Da-Tian

    2017-01-01

    Arsenic is naturally occurring toxic metalloid and drinking As2 O3 containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease, hypertension, and cancer. On the contrary, As2 O3 has been an ancient drug used in traditional Chinese medicine with substantial anticancer activities, especially in the treatment of acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As2 O3 action in solid cancer cells, such as oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of tumor and nontumor cells from the oral cancer patients and treated the cells with As2 O3 alone or combined with dithiothreitol (DTT). The results showed that 0.5 μM As2 O3 plus 20 μM DTT caused a significant cell death of oral cancer cells but not the nontumor cells. Also As2 O3 plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in oral cancer cells. On the other way, As2 O3 also triggered endoplasmic reticulum stress and increased the levels of glucose-regulated protein 78, calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As2 O3 on killing oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in oral cancer therapy and worth further investigations. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 17-27, 2017.

  15. 三氧化二砷纳米粒子对直肠癌作用的实验研究%Study on anticancer effect of arsenic trioxide nanoparticles on rectal cancer

    Institute of Scientific and Technical Information of China (English)

    梁桃; 陈颖颖; 薄挽澜

    2010-01-01

    目的 探讨三氧化二砷纳米粒子在体外、体内对直肠癌的抗癌作用.方法 Annexin V-FITC/PI染色流式细胞术检测三氧化二砷纳米粒子诱导直肠癌细胞HR8348凋亡情况;建立HR8348细胞裸鼠皮下移植瘤模型,监测给药后肿瘤体积的变化,并通过对肿瘤组织标本Ki67染色和TUNEL染色检测肿瘤细胞增殖和凋亡情况.结果 流式细胞术结果显示,4.0 μmol/L三氧化二砷纳米粒子诱导直肠癌细胞凋亡率为7.02%,高于对照组(1.76%),P<0.05,三氧化二砷纳米粒子体外可诱导直肠癌细胞的凋亡.在体内,三氧化二砷纳米粒子可抑制HR8348裸鼠皮下移植瘤的生长,4.0 μmol/L三氧化二砷纳米粒子组增殖指数(31.61%)低于对照组(66.75%),而凋亡指数(19.21%)高于对照组(6.47%),P<0.05.可抑制肿瘤细胞的增殖,诱导细胞凋亡.结论 在直肠癌中,三氧化二砷纳米粒子通过抑制增殖,诱导凋亡而发挥抗癌作用,是直肠癌治疗的良好药物.%Objective To investigate the anticancer effect of arsenic trioxide nanoparticles on rectal cancer in vitro and in vivo. Methods In cultured rectal cancer cells HR8348, flow cytometry were used to evaluate proliferation inhibitory and proapoptotic effect of arsenic trioxide nanoparticles; Rectal cancer xenograft model was established by s.c. injection of HR8348 cells into nude mice. The tumor volume was monitored after exposure to arsenic trioxide nanoparticles, Ki67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue. Results The data of flow cytometry indicate that cancer cell apoptosis induced by 4.0 μmol/L arsenic trioxide nanoparticles was 7.02%, higher than by control group ( 1.76% ),P <0.05. In vivo, arsenic trioxide nanoparticles can inhibit the growth of HR8348 nude mice. In the group of 4. 0 μmol/L arsenic trioxide nanoparticles ,proliferation index (31.61%) was lower than in the control group (66.75%), while the

  16. Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

    Science.gov (United States)

    Chen, Fei-Yan; Yi, Jing-Wei; Gu, Zhe-Jia; Tang, Bin-Bing; Li, Jian-Qi; Li, Li; Kulkarni, Padmakar; Liu, Li; Mason, Ralph P.; Tang, Qun

    2016-03-01

    On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced

  17. The enhancement of sensitivity of HL-60 cells to arsenic trioxide by Bcl-2 siRNA%以Bcl-2为靶标siRNA提高HL-60细胞对三氧化二砷敏感性的探讨

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study whether the small-interference RNA (siRNA) targeting against Bcl-2 gene can enhance sensitivity of HL-60 cell to arsenic trioxide. Methods: SiRNA was transferred into the HL-60 cells. At 6 h after transfection, the cells were cultured with arsenic trioxide. The cell growth of the HL-60 cells was detected using MTT at 24, 48 and 72 h, respectively.The levels of the Bcl-2 protein and reactive oxygen species (ROS), as well as of the membrane potential of the mitochondrion were determined by flow cytometry. Results: The Bcl-2 siRNA significantly increased the inhibitory action of arsenic trioxide on growth of HL-60 cells. The combination of siRNA with arsenic trioxide resulted in decrease of the Bcl-2 protein level and increase of the ROS level, as well as significant descending of the membrane potential of mitochondrion of HL-60 (P < 0.05).Conclusion: The siRNAtargeting Bcl-2 can increase the sensitivity of the HL-60 leukemia cells to arsenic trioxide by inhibiting the expression of Bcl-2 protein.

  18. Aquaporin 9, a promising predictor for the cytocidal effects of arsenic trioxide in acute promyelocytic leukemia cell lines and primary blasts.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Yoshino, Yuta; Hatta, Yoshihiro; Horikoshi, Akira; Aizawa, Shin; Takeuchi, Jin; Toyoda, Hiroo

    2013-06-01

    A close correlation between the cytocidal effects of arsenic trioxide (ATO) and aquaporin-9 (AQP9) expression levels has been proposed, yet detailed studies are still needed to confirm this association. Thus, in the present study, the correlation between the expression levels of AQP9 and sensitivity to ATO was investigated using two acute promyelocytic leukemia (APL) cell lines, NB4 and HT93A, as well as primary APL cells from newly diagnosed and relapsed APL patients. A substantially higher sensitivity to ATO-mediated induction of apoptosis was observed in the NB4 cells when compared to that in the HT93A cells. In addition, markedly higher expression levels of AQP9, as assessed using flow cytometry, along with more intracellular arsenic accumulation, were observed in the NB4 cells. More importantly, similar to APL cell lines, the trend of expression levels of AQP9 correlated closely with the differential sensitivity to ATO-mediated induction of apoptosis in primary APL cells. In contrast, no correlation was observed between ATO sensitivity associated with AQP9 expression levels and the expression profiles of cell surface markers as well as chromosomal alterations. These results provide direct evidence that the expression levels of AQP9, rather than other biomarkers such as cell surface markers and chromosomal alterations, correlate closely with the sensitivity to ATO in both APL cell lines and primary blasts. These findings suggest that the AQP9 expression status of APL patients is a predictive marker for the successful outcome of ATO treatment, since AQP9 plays a pivotal role in various arsenite-mediated biological effects on normal and cancer cells. Moreover, flow cytometry may be a new convenient and valuable tool for analyzing the AQP9 status of APL patients compared to current methods such as western blotting.

  19. Stathmin is involved in arsenic trioxide-induced apoptosis in human cervical cancer cell lines via PI3K linked signal pathway.

    Science.gov (United States)

    Wang, Xi; Ren, Ji-Hong; Lin, Fang; Wei, Jun-Xia; Long, Min; Yan, Lin; Zhang, Hui-Zhong

    2010-09-15

    Although the mechanisms of arsenic trioxide (As2O3)-induced apoptosis have been elucidated extensively in hematologic cancers, those in solid tumors have yet to be clearly defined. In the present study, we show that As2O3 triggers apoptosis through the intrinsic pathway and significantly downregulates stathmin expression. Decreased stathmin expression is necessary for the dissipation of mitochondrial membrane potential (Δ ψm), the translocation of cytochrome C from the mitochondria to the cytosol, and subsequent cell death. Overexpression of wild type stathmin effectively delays As2O3-mediated mitochondrial events. Conversely, expression of a small interfering RNA (siRNA) targeting stathmin enhances As2O3-triggered apoptosis in cell culture and in mouse models. Furthermore, we demonstrate that As2O3-induced stathmin downregulation is mediated through the phosphatidylinositol-3-kinase (PI3K) signaling pathway, and that a PI3K inhibitor effectively attenuated stathmin downregulation and cell apoptosis upon As2O3-treatment. These data support a stathmin-dependent pathway of As2O3-mediated cell death in solid tumor cells, and indicate that stathmin is a target of the PI3K/Akt pathway in cervical cancer cells. All these results may provide a rationale for improving the efficacy of As2O3 as a therapeutic agent through combination treatment with stathmin inhibition or PI3K/Akt inhibitors.

  20. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  1. The influence of joint application of arsenic trioxide and daunorubicin on primary acute promyelocytic leukaemia cells and apoptosis and blood coagulation of cell strain.

    Science.gov (United States)

    Zhang, Xiaojuan; Qin, Na; Chen, Xinghua; Guo, Shuxia

    2015-05-01

    This test cultivated three groups of acute promyelocytic leukemia (APL) and NB4 cells in liquid in vitro, processed them with arsenic trioxide (ATO), daunorubicin (DNR), ATO+DNR respectively, and then set up blank control group. Apoptosis of cells in each group was observed using flow cytometry, procoagulant activity of APL and NB4 cells in each group was detected with recalcification time, and expressions of tissue factor (TF), thrombomodulin and annexin II of NB4 cells in each group were measured using ELISA method. The results showed that the apoptosis rate increased 4-8 times compared with blank control group after processing APL and NB4 cells with ATO and DNR; procoagulant activity decreased obviously; and expression of TF and annexin II of NB4 cells reduced significantly (P<0.05). We concluded that combination of ATO and DNR could promote APL and NB4 cell apoptosis effectively without aggravating blood coagulation disorders, which might improve coagulation function of APL by inhibiting coagulation and hyperfibrinolysis through reducing expression of TF and annexin II. This drug combination may be a safe and effective method in the treatment of APL of primary high white blood cells type.

  2. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

    Science.gov (United States)

    Poiré, Xavier; Moser, Barry K; Gallagher, Robert E; Laumann, Kristina; Bloomfield, Clara D; Powell, Bayard L; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A; Tallman, Martin S; Appelbaum, Frederick R; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-07-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, < 0.5. Neither FLT3 mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of FLT3 mutation type or level, initial white blood cell count, PML-RARA isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy.

  3. Potentiation of arsenic trioxide-induced apoptosis by 8-bromo-7-methoxychrysin in human leukemia cells involves depletion of intracellular reduced glutathione

    Institute of Scientific and Technical Information of China (English)

    Guangfen Xiao; Xueyuan Tang; Chenjiao Yao; Chenghong Wang

    2011-01-01

    The novel chrysin analog 8-bromo-7-methoxychrysin (BrMC) has been reported to induce apoptosis of various cancer cell lines.Arsenic trioxide (ATO) treatment induces clinical remission in acute promyelocytic leukemia patients.The combination of ATO with other agents has been shown to improve therapeutic effectiveness in vitro and in vivo.In this report,the mechanism of apoptosis induced by treatment with ATO alone or in combination with BrMC was studied in U937,HL-60,and Jurkat cells.Our results demonstrated that BrMC cooperated with ATO to induce apoptosis in human leukemia cells.This co-treatment caused mitochondrial transmembrane potential dissipation and stimulated the mitochondrial apoptotic pathway,as evidenced by cytochrome c release,down-regulation of X-linked inhibitor of apoptosis (XIAP) and Bcl-XL,and up-regulation of Bax.BrMC alone or in combination with ATO,decreased Akt phosphorylation as well as intracellular reduced glutathione (GSH) content.The thiol antioxidant N-acetylcysteine and exogenous GSH restored GSH content and attenuated apoptosis induced by co-treatment with ATO plus BrMC.In contrast,the non-thiol antioxidant butylated hydroxyanisole and mannitol failed to do so.These findings suggest that GSH depletion explains at least in part the potentiation of ATO-induced apoptosis by BrMC.

  4. Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy.SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

  5. Anti-tumor effect of arsenic trioxide on subcutaneously implanted Lewis lung carcinoma in mice%三氧化二砷对小鼠皮下移植性肺癌抑制及其机制的探讨

    Institute of Scientific and Technical Information of China (English)

    宋玉华; 彭鹏; 王清波; 邱少敏

    2012-01-01

    To evaluate the anti-angiogenesis effects of arsenic trioxide on transplanted lung carcinoma in mice. METHODS: Lewis lung carcinoma cells (LLC cells) were transplanted subcutaneously to C57BL/6 mice to generate tumors. Sixty mice were randomly divided into 3 groups (n = 20):negative control group,positive control group and arsenic trioxide treatment group. The tumor weight of the mice was measured respectively during the therapy. The tumor growth inhibition rates of each group were calculated. The expressions of VEGF and EGFR in the lung cancer tissue were examined by immunohistochemical method. RESULTS:The tumor weight of arsenic trioxide treatment group, positive control group and negative control group were (1 420±60),(l 500±80) and (2 420 ± 190) mg respectively. Compared with negative control group,the tumor weight of arsenic trioxide treatment group and positive control group were significantly lower than that of the negative control group (P0. 05). The expression of VEGF (63. 10 ± 5. 32)% and EGFR (68. 33 ±5. 99)% in arsenic trioxide treatment group were significantly less than those in negative control group [(76. 33 ± 10. 3)%,(80. 50±10. 21)%,P<0. 05]. CONCLUSION: Arsenic trioxide has strong inhibition effect on tumor growth;This effect was probably mediated by downregulating the expression of VEGF and EGFR.%目的:探讨三氧化二砷(AS2O3)对小鼠肺癌移植瘤的抑制作用,进一步分析其抗血管生成的可能机制.方法:建立Lewis肺癌小鼠移植瘤模型,60只小鼠随机分成阴性对照组、阳性对照组和AS2O3治疗组3组(每组20只),应用AS2O3治疗后,观察肿瘤生长情况计算抑瘤率,免疫组化法检测肿瘤组织内血管内皮生长因子(VEGF)和表皮生长因子受体(EGFR)的表达.结果:AS2O3组、阳性对照组、阴性对照组的瘤质量分别为(1 420±60)、(1 500±80)和(2 420±190) mg;AS2O3组和阳性对照组的瘤质量较阴性对照组明显减轻,P<0.05;AS2O3组的抑瘤率(52

  6. Clinical Study of Transarterial Chemoembolization for Primary Hepatic Carcinoma with Lipiodol-arsenic Trioxide Emulsion%亚砷酸-碘油乳剂经动脉栓塞治疗原发性肝癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    周玉斌; 吴丹明; 柳青峰

    2009-01-01

    Objective To evaluate the effect and toxicity of lipiodol-arsenic trioxide emulsion on the treatment of primary hepatic carcinoma. Methods Arsenic trioxide 20mg and lipiodol were fully mixtured into lipiodol-arsenic trioxide emulsion,which were injected into hepatic artery by catheters in 58 patients with primary hepatic carcinoma. If the patients' conditions progressed(tumor got larger or AFP increased),Anthracyctine would be used simultaneously. The effect and toxicity were observed. Results After 1~3 times of thera-py only with lipiodol-arsenic trioxide emulsion in all of 58 patients,objective response rate was 20.7% with 12 eases of PR,36 cases of NC and 10 cases of PD. AFP decreased from(11109.36±2920.82) IU/mL to(10001.61±2880.67) IU/mL averagely(P>0.05). An-thracycline was applied in 22 patients,and tumors got smaller in 16 cases after that. AFP decreased from (13901.11±4862.26) IU/mL to(5470.63±2597.79) IU/mL averagely(P0.05.22例患者在治疗中加用蒽环类药物,16例病灶有不同程度的缩小,AFP平均由(13901.11±4862.26)IU/mL降至(5470.63±2597.79)IU/mL,P<0.05.主要毒副反应为发热、恶心呕吐、肝区疼痛、血细胞减少及转氨酶升高等,全组未见不可逆毒副反应.结论 经肝动脉途径应用亚砷酸一碘油乳剂栓塞治疗原发性肝癌疗效较好,毒副反应较小,是一种较理想的微创治疗原发性肝癌的方法.

  7. Anti-tumor Effect and Potential Mechanism of Arsenic Trioxide on SMMC-7721 Cells of Human Liver Cancer in Vivo and Vitro

    Institute of Scientific and Technical Information of China (English)

    Shen Bo

    2014-01-01

    Objective:To observe the anti-tumor effect of arsenic trioxide (As2O3) on SMMC-7721 cells of patients with liver cancer in vivo and vitro. Methods: Methyl Thiazolyl Tetrazolium (MTT) method, fluorescence microscope, FITC-AnnexinⅤ/PI double-tagging method and colorimetry were used to detect the survival rate, morphological change, apoptosis and Caspase-3 activity change of SMMC-7721 cells in different concentration of As2O3 for 48 h, respectively. As2O3 was injected into the transplanted tumors in nude mice with SMMC-7721 hepatoma cells to observe the growth of tumors. The mice were sacriifced after 12 d, followed by the extirpation and weighing of the tumors. Then Bcl-2, Bax and Caspase-3 expression were detected by immunohistochemistry. Results: As2O3 could obviously inhabit the proliferation of SMMC-7721 cells, with inhibition concentration (IC) being (18.17±2.10) μmol/L. Microscope showed typical morphological change of cell apoptosis and As2O3 treatment group was evidently higher than control group in apoptosis rate of SMMC-772 cells, suggesting that As2O3 could improve SMMC-772 cell activity. Internal injection of As2O3 into transplanted tumors in nude mice with SMMC-7721 hepatocellular lines could remarkably inhabit the growth of tumors with inhabiting rate being 52.37%, and immunohistochemistry also revealed that As2O3 could apparently up-regulate cell apoptosis-related Bax and Caspase-3 expression, and down-regulate Bcl-2 expression. Conclusion: As2O3 can inhabit the growth and in vivo oncogenesis of hepatoma SMMC-7721 cells, and induce SMMC-7721 cell apoptosis.

  8. Review of arsenic trioxide effect on solid cancer%三氧化二砷抗实体肿瘤的研究概况

    Institute of Scientific and Technical Information of China (English)

    张晨; 凌昌全

    2003-01-01

    Clinical trials have demonstrated that arsenic trioxide(As2O3) was effective in the treatment of acute promyelocytic leukemia(APL), based on this facts, studies have been carried out to study its role in the treatment of solid cancer at home and abroad. Primary in vitro study showed that As2O3 could treat the cancer of digestive system such as hepatoma, esophageal carcinoma, gastric cancer, and the cancer of urinary and reproductive system such as cervical cancer, ovarian cancer, bladder transitional carcinoma,as well as lung cancer, breast cancer, prostate cancer, etc. The mechanism of As2O3 actions may be the induction of apoptosis, the inhibition of growth and the promotion of differentiation of solid cancers. This article reviews on As2O3 in treatment of solid cancer.%三氧化二砷(As2O3)临床治疗急性早幼粒细胞白血病(APL)有极好的疗效,在此基础上国内外开展了将其应用于实体瘤的研究.初步结果显示,As2O3对肝癌、食管癌、胃癌等消化系统肿瘤有明显的治疗作用;对宫颈癌、卵巢癌、膀胱癌等泌尿生殖系统肿瘤,以及肺癌、乳腺癌、前列腺癌等其他肿瘤,也显示了抑制细胞增殖并诱导凋亡的作用,本文对此进行了综述.

  9. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  10. Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

    Science.gov (United States)

    Vineetha, Vadavanath Prabhakaran; Girija, Seetharaman; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2014-03-01

    Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

  11. Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic trioxide-based therapy in relapsed acute promyelocytic leukemia patients.

    Science.gov (United States)

    Lou, Yinjun; Ma, Yafang; Sun, Jianai; Ye, Xiujin; Pan, Hanzhang; Wang, Yungui; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; He, JingSong; Tong, Hongyan; Jin, Jie

    2015-11-01

    The aim of the study is to better understand the mechanism of relapse and acquired clinical resistance to arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Thirty relapsed acute promyelocytic leukemia (APL) patients were followed. Fifteen patients experienced two or more relapses; nine patients had clinical resistance to ATO-based therapy. The frequency and clinical significance of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) mutational status using Sanger sequencing were evaluated. Overall, eight different types of mutations in the RARA region (V218D, R272Q, T278A, T291I, N299D, R294W, A300G, and L220_F228delinsP) were identified in 11 patients. Eight missense mutations (L211P, C213R, S214L, A216V, L217F, D219H, S221G, and D241G) were found in the PML portion of PML-RARA in 14 patients, with A216V as the predominant mutation. Eight patients were found to harbor both PML and RARA mutations over the course of the disease. The PML-region mutations were associated with response to ATO-based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P = 0.013). Notably, one case sampled at nine different time points showed alternating clonal dominance over the course of treatment. This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance.

  12. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Wu, Wen-Jeng [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Huang, Huei-Sheng, E-mail: huanghs@mail.ncku.edu.tw [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

    2015-05-15

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF

  13. Potential role of sodium-proton exchangers in the low concentration arsenic trioxide-increased intracellular pH and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Carmen Aravena

    Full Text Available Arsenic main inorganic compound is arsenic trioxide (ATO presented in solution mainly as arsenite. ATO increases intracellular pH (pHi, cell proliferation and tumor growth. Sodium-proton exchangers (NHEs modulate the pHi, with NHE1 playing significant roles. Whether ATO-increased cell proliferation results from altered NHEs expression and activity is unknown. We hypothesize that ATO increases cell proliferation by altering pHi due to increased NHEs-like transport activity. Madin-Darby canine kidney (MDCK cells grown in 5 mmol/L D-glucose-containing DMEM were exposed to ATO (0.05, 0.5 or 5 µmol/L, 0-48 hours in the absence or presence of 5-N,N-hexamethylene amiloride (HMA, 5-100 µmol/L, NHEs inhibitor, PD-98059 (30 µmol/L, MAPK1/2 inhibitor, Gö6976 (10 µmol/L, PKCα, βI and μ inhibitor, or Schering 28080 (10 µmol/L, H(+/K(+ATPase inhibitor plus concanamycin (0.1 µmol/L, V type ATPases inhibitor. Incorporation of [(3H]thymidine was used to estimate cell proliferation, and counting cells with a hemocytometer to determine the cell number. The pHi was measured by fluorometry in 2,7-bicarboxyethyl-5,6-carboxyfluorescein loaded cells. The Na(+-dependent HMA-sensitive NHEs-like mediated proton transport kinetics, NHE1 protein abundance in the total, cytoplasm and plasma membrane protein fractions, and phosphorylated and total p42/44 mitogen-activated protein kinases (p42/44(mapk were also determined. Lowest ATO (0.05 µmol/L, ~0.01 ppm used in this study increased cell proliferation, pHi, NHEs-like transport and plasma membrane NHE1 protein abundance, effects blocked by HMA, PD-98059 or Gö6976. Cell-buffering capacity did not change by ATO. The results show that a low ATO concentration increases MDCK cells proliferation by NHEs (probably NHE1-like transport dependent-increased pHi requiring p42/44(mapk and PKCα, βI and/or μ activity. This finding could be crucial in diseases where uncontrolled cell growth occurs, such as tumor growth, and

  14. Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As sub 2 O sub 3 )

    Energy Technology Data Exchange (ETDEWEB)

    Reichl, F.X.; Kreppel, H.; Fichtl, B.; Forth, W. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Szinicz, L. (Akademie des Sanitaets- und Gesundheitswesens der Bundeswehr, Garching (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie)

    1990-06-01

    In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As{sub 2}O{sub 3}. Four groups of ten mice each received As{sub 2}O{sub 3}, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose + 0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As{sub 2}O{sub 3} only died within 22 h. The mean survival time was 12.4 h. In mice receiving As{sub 2}O{sub 3} and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning. (orig./MG).

  15. 亚砷酸和顺铂对骨肉瘤MG-63细胞生长的抑制作用比较%Comparison of arsenic trioxide and cisplatin on inhibiting osteosarcoma MG-63 cells

    Institute of Scientific and Technical Information of China (English)

    李雪松; 刘贾昆; 王文波

    2010-01-01

    率组间比较差异有统计学意义(F值分别为54.579、43.429、21.795,P<0.05或<0.01);对G1期抑制率(%)亚砷酸(78.26±5.24)和顺铂(80.48±2.81)与对照组(57.49±6.65)比较明显升高(P<0.05或<0.01).结论 亚砷酸和顺铂都可抑制骨肉瘤MG-63细胞生长,诱导细胞凋亡;亚砷酸作用快于顺铂,亚砷酸和顺铂对MG-63细胞的抑制作用发生在细胞周期中的G1期.%Objective To explore the inhibiting effects of arsenic trioxide and cisplatin on MG-63 cells. Methods Using MTT assay,flowcytometry,phase contrast microscopy and electron microscopy methods,the therapeutic effect of arsenic trioxide was studied for the osteosarcoma in the cultured MG-63 cells in vitro,and compared these effects with cisplatin. The inhibitory rotes of cell growth and the effect of apoptosis and cell cycle were compared between arsenic trioxide and cisplatin on MG-63 cells. Results The contrast phase microscope revealed the adhesion ability of normal groups was good and cellular morphology showed epithelium cells. But the celhdar morphology showed irregular arrangement in arsenic trioxide groups and cytoplasmic vacuoles in cisplatin group. Electron microscope revealed the globular plasmalemma ecphymas in cell surface of control groups,the enlarged crista mitochondriales and the double-deck membrane structure appeared clearly. But electron microscope revealed globular plasmalemma processes in cell surface of arsenic trioxide groups,thinned crista mitochondriales and clearly seen karyopycnosis and nuclear membrane of apoptotic cells. The globular plasmalemma processes in cell surface of cisplatin groups were separated,nuclear membrane thickened and chromatin were in sandy shape. Both arsenic trioxide and cisplatin inhibited effectively MG-63 cells growth. There was a significant difference in different groups of inhibition ratios to the growth of cells(all P < 0.05). In 2,4,8,16,32,64,128 hours,the inhibition ratios(%) of arsenic trioxide(56.31±0.03,70.00±0.06,79.84±0

  16. Arsenic

    Science.gov (United States)

    Arsenic is a natural element found in soil and minerals. Arsenic compounds are used to preserve wood, as pesticides, and in some industries. Arsenic can get into air, water, and the ground from wind- ...

  17. Apoptotic Efficacy of Etomoxir in Human Acute Myeloid Leukemia Cells. Cooperation with Arsenic Trioxide and Glycolytic Inhibitors, and Regulation by Oxidative Stress and Protein Kinase Activities

    Science.gov (United States)

    Estañ, María Cristina; Calviño, Eva; Calvo, Susana; Guillén-Guío, Beatriz; Boyano-Adánez, María del Carmen; de Blas, Elena; Rial, Eduardo; Aller, Patricio

    2014-01-01

    Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25–200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic

  18. Effects of HBV X gene and arsenic trioxide on the expression of p53 in cultured HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    LEI Jian-hua; HE Xing-e; YANG Xu; ZHANG Min; LIAN Jun; LUO Hong-yu; WANG Wen-long

    2007-01-01

    Background Hepatitis B virus(HBV)X protein(HBx)and p53 could mutually down-regulate at transcriptional level and HBx could bind with p53 protein within its transactivation domain and inhibit the function of p53 protein.In recent years,effects of arsenic trioxide(As2O3)on the expression of p53 protein have been widely studied,while little is known about the activity of p53 protein.This study was undertaken to delineate the effect of HBV X gene and As2O3 on p53 protein expression(level and activity)in HepG2 cells by small hairpin RNA(shRNA)-mediated RNA interference(RNAi)technique.Methods Cell line HepG2 and cells with stable expression of HBV X gene(HepG2-X)were treated with 2 μmol/L As2O3,with corresponding untreated cells serving as controls.Cell lysates and nuclear extracts were extracted.Total level and the relative activity of p53 protein were detected by modified enzyme-linked immunosorbent assay(ELISA).HBV X gene sequence-specific shRNA expression vector(pXi-1 and pXi-2)and sequence-unrelated control(pXi-3)were transfected into HepG2-X.Single cell clone with stable expression of shRNA was selected and exposed to propagating culture.The effect of As2O3 on p53 protein expression and activity was re-observed.Results Total p53 protein level was up-regulated and its relative activity ratio was enhanced by As2O3 in HepG2 and HepG2-X cells.The total p53 protein level induced by As2O3 was up-regulated by HBV X gene expression,while its relative activity was significantly suppressed.The suppression was removed after HBV X gene expression was repressed by shRNA.Conclusions As2O3 up-regulates p53 protein expression and enhance its activity.HBV X up-regulates As2O3 induced-p53 protein expression while suppresses its activity.

  19. 三氧化二砷对支气管哮喘免疫及气道炎症的调控%Regulation on immunity and airway inflammation of bronchial asthma by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    李坑; 龚素波; 徐礼; 张莉; 向旭东

    2011-01-01

    Bronchial asthma (asthma) is a kind of chronic inflammation of airway, which was involved in many kinds of cells and cellular elements, such as eosinophils, T lymphocytes, neutrophil granulocytes, mastocytes, alveolar epithelial cells, and so on. Arsenic trioxide can improve the asthmatic mice's pulmonary function in experiment, and own the ability of hold the patients' asthmatic symptoms in a better state for a long time. The recent researchs indicated that the arsenic trioxide can regulate immunity and inhibit airway inflammation through many effective processes, such as inhibiting humoral immunity and proliferation of T lymphocytes at skin and lung, down-regulating expression of inflammatory factors (IL-17, IL-18, IL-23,etc), and inducing apoptosis of neutrophil granulocytes by endoplasmic reticulum stress pathway. The newest studies about the regulation on immunity and airway inflammation of asthma by arsenic trioxide were summarized, and some possible research orientation was previewed.%支气管哮喘(简称哮喘)是一种由多种细胞(嗜酸粒细胞、T细胞、中性粒细胞、肥大细胞及肺泡上皮细胞等)及细胞组分参与的气道慢性炎症性疾病.三氧化二砷在动物实验中能改善哮喘小鼠的肺功能,在临床治疗中能使患者的哮喘症状得到长期控制.新近研究表明:三氧化二砷能明显抑制小鼠的体液免疫反应,抑制小鼠的肺、皮肤等组织的T细胞增殖,能下调IL-17、IL-18和IL-23等多种炎症因子的分泌,并且通过内质网应激途径诱导中性粒细胞凋亡,从而调节免疫,抑制炎症.文章综述了三氧化二砷调控哮喘免疫及气道炎症的最新研究进展,并进行了展望.

  20. Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide.

    Science.gov (United States)

    Eghtedar, Alireza; Rodriguez, Ildefonso; Kantarjian, Hagop; O'Brien, Susan; Daver, Naval; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Kadia, Tapan; Pierce, Sherry; Cortes, Jorge; Ravandi, Farhad

    2015-05-01

    The incidence and pattern of secondary neoplasms in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA)-containing regimens is not well described. We compared 160 patients with APL treated with ATRA plus idarubicin (n = 54) or ATRA plus arsenic trioxide (ATO) (n = 106) for the incidence of secondary cancers per unit time of follow-up. Median follow-up times for the two cohorts were 136 and 29 months, respectively. Nine patients developed secondary cancers in the chemotherapy group. These included two breast cancers, three myelodysplastic syndromes/acute myeloid leukemia, one vulvar cancer, one prostate cancer, one colon cancer and one soft tissue sarcoma. A melanoma and one pancreatic cancer developed in the ATO group. We conclude that treatment of patients with APL using the non-chemotherapy regimen of ATRA plus ATO is not associated with a higher incidence of secondary cancers (p = 0.29) adjusted for unit time of exposure.

  1. 三氧化二砷与HAG方案治疗骨髓增生异常综合征的对比研究%Comparision of between arsenic trioxide and HAG regimen in the treatment of myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    张静; 徐敬根

    2012-01-01

    Objective HAG regimen ( Homoharringtonine and Low-dose Cytosine Arabinoside Combined with G-CSF or GM-CSF)is an important regimen for refractory anemia with excess blasts of myelodysplastic syndrome ( MDS-RAEB), but the side effect is severe. This study aims to compare the short-term efficiency, toxicity and side effect between arsenic trioxide and HAG regimen in the treatment of MDS-RAEB. Methods All patients were randomly divided into two groups: A group and B group. 20 cases in A group:were treated with HAG regimen for remission induction and consolidation therapy. 20 cases in B group were Arsenic trioxide was administered 10 mg/d, intravenous infusion, 14 times per month, 2 ~3 weeks interval for a course of treatment. Results Response rates were 70. 0% (group A) and 80. 0% ( group B). The response rate between two groups were not statistical difference (P > 0. 05). The incidences of infection which exceed grade H were 43. 8% ( group A) and 9. 09 % (group B) , and the incidences of hemorrhage which exceed grade II were 37. 5% ( group A) , and 12. 1% ( group B) , with statistical difference between the two groups(P<0.05). Conclusion The therapeutic efficiency of arsenic trioxide was similarly to that of HAG regimen and side-effect of arsenic trioxide were milder than that of HAG regimen.%目的 HAG方案是目前治疗骨髓增生异常综合征难治性贫血伴原始细胞增多(MDS-RAEB)的重要化疗方案之一,但不良反应仍较大.本研究的目的是比较三氧化二砷与HAG治疗MDS-RAEB的近期疗效和不良反应.方法 将40例骨髓增生异常综合征患者随机分成A组(预激方案20例)和B组(三氧化二砷20例),化疗2~3个周期,评价疗效.结果 A组有效率70.0%,B组有效率80.0%,两组比较,差异无统计学意义(P>0.05);A组≥Ⅱ级感染的发生率为43.8%,≥Ⅱ级出血(需予局部压迫、药物止血或血小板输注等相应处理)的发生率为37.5 %;B组≥Ⅱ级感染发生率为9.09

  2. Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.

    Science.gov (United States)

    Si, Lu; Jiang, Fei; Li, Yuan; Ye, Xianqing; Mu, Juan; Wang, Xingxing; Ning, Shilong; Hu, Chunyan; Li, Zhong

    2015-09-01

    Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, however, regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we report that As(2)O(3) attenuates the migratory and invasive capacities of breast cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro and in vivo, as determined by the increased expression of the epithelial marker, E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through demethylation. Over-expression of miR-200c enhances the expression of E-cadherin and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231 cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR-200c and MET, the results establish the anti-migration/invasion potential of arsenic trioxide.

  3. Nine-month Angiographic and Two-year Clinical Follow-up of Novel Biodegradable-polymer Arsenic Trioxide-eluting Stent Versus Durable-polymer Sirolimus-eluting Stent For Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Li Shen

    2015-01-01

    Full Text Available Background: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES, compared with traditional sirolimus-eluting stent (SES. Methods: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF, and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR by telephone visit and late luminal loss (LLL at 9-month by angiographic follow-up. Results: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980. Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028. There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008. Conclusions: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

  4. 亚砷酸腔内注射治疗恶性胸腔积液的临床观察%Clinical observation of the treatment of malignant pleural effusion by injecting arsenic trioxide into pleural cavity

    Institute of Scientific and Technical Information of China (English)

    孟令新; 迟玉华; 丁兆军; 杨淑光; 王传艳; 张桂芳

    2014-01-01

    目的:评价亚砷酸胸腔注射治疗恶性胸腔积液的临床价值。方法:恶性胸腔积液患者68例,均经细胞学和病理学确诊。随机分为治疗组和对照组,在胸膜腔积液充分引流后,治疗组36例,胸膜腔内注射亚砷酸10-20mg,每天或隔日1次,连续3次。对照组32例,胸膜腔内注射博莱霉素30mg/ m2,7天1次,共1-2次。观察疗效、毒副反应、生活质量。结果:治疗组 CR 10例(27.78%),PR 16例(44.44%),总有效率为72.22%(26/36);对照组 CR 8例(25.00%),PR 15例(46.88%),总有效率为71.88%(23/32),两组有效率差异无显著性(P ﹥0.05)。治疗组注药后胸痛反应明显低于对照组(P ﹤0.05),胃肠道反应、骨髓抑制、发热反应两组间无明显差异(P ﹥0.05)。治疗后两组 KPS 评分均有增加,治疗前后比较有明显差异(P ﹤0.05)。结论:亚砷酸胸腔注射治疗恶性胸腔积液是一种有效、安全的方法。%Objective:To evaluate the clinical value of arsenic trioxide in treating malignant Pleural effusion by in-jecting into Pleural cavity. Methods:Sixty - eight Patients,required to have a cytologically Positive Pleural effusion or a Positive Pleural bioPsy in the Presence of an exudative effusion. After the accumulation of Pleural fluid had been ad-equately drained,36 Patients were randomized to Arsenic trioxide grouP,receiving arsenic trioxide 10 - 20mg,once a day or once two days,on 3 successive times,which were administered via chest tube or directly injected into Pleural cavity. Then the efficacy,toxicity and Perform ancestatus were evaluated. Results:In the Arsenic trioxide grouP,10 Pa-tients(27. 78% )achieved CR and 16 Patients(44. 44% )PR,the overall resPonse rate was 72. 22%(26 / 36). The control grouP 8 Patients(25. 00% )achieved CR and 15 Patients( 46 . 88 % )PR,and the overall resPonse rate was 71. 88%(23 / 32). The two grouPs had no significant

  5. Improvement on the Determining Method of Particulate Arsenic and Arsenic Compounds and Arsenic Trioxide Vapour in Atmosphere%测定环境空气中砷及其化合物的方法改进

    Institute of Scientific and Technical Information of China (English)

    郎雅娣; 梁静; 鹿海峰

    2013-01-01

    对《空气和废气监测分析方法》中砷的采样和测定方法进行了改进,并在云南某炼铜厂环境空气中含砷监测进行了实际验证.结果表明,方法的检出限、精密度、准确度均能满足测定的要求,并且更适合测定高浓度砷.%The "air emission monitoring and analysis methods" in the sampling and testing methods for arsenic has been improved. The method has been verified in a copper smelter in Yunnan. The detection limits, precision, accuracy can content the detect demand and this method is more suitable for determination of high concentrations of arsenic.

  6. 三氧化二砷在消化系恶性肿瘤治疗中的作用%Role of arsenic trioxide in the treatment of malignant tumors of the digestive system

    Institute of Scientific and Technical Information of China (English)

    常圆; 杨甜; 关景明

    2012-01-01

    三氧化二砷(arsenic trioxide,As2O3),中药名为砒霜,在临床上的应用有悠久的历史,经过多年的实验室研究和临床应用,AS2O3在抗肿瘤方面有确切的疗效,他是治疗急性早幼粒细胞白血病的有效药物之一,且不良反应较小,其主要机制为诱导细胞凋亡.目前As2O3已用于多种实体肿瘤的治疗,且在消化系肿瘤如肝癌的临床治疗中,疗效确切.近年来,在消化系统肿瘤的体外细胞系和体内动物模型的研究中均发现,As2O3能够诱导胃癌、胰腺癌、肝癌和结肠癌细胞凋亡,同时对癌细胞的生长起抑制作用.因此,研究As2O3在消化系恶性肿瘤防治中的作用具有重要意义.本文结合国内外文献对As2O3在治疗消化系恶性肿瘤中的作用作一综述.%Arsenic trioxide (As2O3), also named arsenic, is a main ingredient of numerous traditional Chinese herbal recipes and has a long history of clinical application. It has positive anticancer effects and is effective in treating acute promyelocytic leukemia without toxic and side effects. As2O3 can induce apoptosis of cancer cells. In recent years, it has been found that As2O3 has an apoptosis-promoting effect on tumor cells in many human solid tumors, including liver cancer. Many in vitro and in vivo studies using digestive tract tumor cell lines or animal model have found that As2O3 can induce apoptosis and inhibit growth of digestive tract cancer cells. Therefore, As2O3 may have an important role in the prevention of malignant tumors of the digestive system. In this article, we discuss the possible cellular and molecular mechanisms by which As2O3 induces apoptosis of digestive tract cancer cells.

  7. Arsenic: a beneficial therapeutic poison - a historical overview.

    Science.gov (United States)

    Thomas, Xavier; Troncy, Jacques

    2009-06-01

    Arsenicals have been used since ancient Greek and Roman civilizations and in the Far East as part of traditional Chinese medicine. In Western countries, they became a therapeutic mainstay for various ailments and malignancies in the 19th and early 20th centuries. Fowler's potassium bicarbonate-based solution of arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid leukaemia until the 1930s. After a decline in the use of arsenic during the mid-20th century, arsenic trioxide was reintroduced as an anticancer agent after reports emerged from China of the success of an arsenic trioxide-containing herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic trioxide was first purified and used in controlled studies in China in the 1970s.Subsequently, randomised clinical trials performed in the United States led to FDA approval of arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukaemia.

  8. [Acute arsenic poisoning].

    Science.gov (United States)

    Montelescaut, Etienne; Vermeersch, Véronique; Commandeur, Diane; Huynh, Sophie; Danguy des Deserts, Marc; Sapin, Jeanne; Ould-Ahmed, Mehdi; Drouillard, Isabelle

    2014-01-01

    Acute arsenic poisoning is a rare cause of suicide attempt. It causes a multiple organs failure caused by cardiogenic shock. We report the case of a patient admitted twelve hours after an ingestion of trioxide arsenic having survived thanks to a premature treatment.

  9. Arsenic

    Science.gov (United States)

    ... found in its pure form as a steel grey metal, arsenic is usually part of chemical compounds. ... imply endorsement by the American Cancer Society. No matter who you are, we can help. Contact us ...

  10. Refractory and recurrent malignancies with arsenic trioxide MDT analysis influence on prognosis%难治及复发性恶性血液病采用三氧化二砷联合化疗对预后影响

    Institute of Scientific and Technical Information of China (English)

    安婕; 唐雯

    2014-01-01

    目的:观察三氧化二砷联合化疗方案治疗难治及复发性恶性血液病的效果。方法:随机从我院2009年6月~2014年6月收治的难治及复发性恶性血液病患者中抽取60例作为研究对象,根据治疗方案将其分为对照组和观察组,每组各30例。其中对照组使用单纯化疗方案治疗,观察组则使用三氧化二砷联合化疗的方案治疗,对比两组的临床效果和毒性反应。结果:经对比,观察组患者的总有效率为86.67%,显著高于对照组的66.67%,差异具有统计学意义(P<0.05)。同时,观察组的毒性反应发生率为30%,显著低于对照组的66.67%,差异具有统计学意义(P<0.05)。结论:对难治及复发性恶性血液病采用三氧化二砷联合化疗治疗具有显著疗效,降低不良反应,有助于改善患者的预后。%Objective: To explore the use of arsenic trioxide and combination in the treatment of refractory and the prognosis of recurrent malignancies effects and adverse reactions. Methods: Random from our hospital in June 2009~June 2014 patients with refractory and recurrent malignancies treated were extracted 60 cases as the research object, according to the treatment plan will be divided into control group and observation group, 30 cases in each group. , including control group using pure chemotherapy regimen for observation group joint solution with arsenic trioxide and chemotherapy treatment,compared two groups of clinical effect and toxic reaction. Results:By contrast, the observation group the total effective rate of the patients were 86.67%, significantly higher than that of control group 66.67%, and the difference is statistically significant(P<0.05). Incidence of toxic effects of at the same time, the observation group was 30%, significantly lower than the control group 66.67%, and the difference is statistically significant (P<0.05). Conclusion: The refractory and recurrent malignancies with

  11. 三氧化二砷联合顺铂治疗恶性胸腔积液的临床研究%A Clinical Study on Arsenic Trioxide Combined with Cisplatin in the Treatment of Malignant Pleural Effusion

    Institute of Scientific and Technical Information of China (English)

    杨雪梅; 陈远航; 曾守群; 戴刚毅; 曾贵林; 孟又胜

    2013-01-01

    Objective To evaluate the efficacy and side-effects of arsenic trioxide combined with eisplatin in treating malignant pleural effusion by injecting it into the pleural cavity.Methods Sixty patients with malignant hydrothorax diagnosed between September 2011 and September 2012 were randomized into two groups.After the accumulation of pleural fluid had adequately drained,30 patients were randomized to treatment group,receiving arsenic trioxide 20 mg plus cisplatin 60 mg once a week for 3 times,and the other 30 patients were randomized to control group,receiving cisplatin 60 mg once a week for 3 times.Then the efficacy and toxicity were evaluated.Results The overall response rates in the treatment group and in the control group were 93.3% and 56.7% (P < 0.05),respectively.The total modification rates in the treatment group and the control group were 70% and 40% (P < 0.05),respectively.There was no difference in toxicity between the two groups.Condusions Pleural cavity infusion of arsenic trioxide combined with cisplatin has combined synergies.The treatment is well tolerated with little adverse toxic reaction.%目的 观察三氧化二砷联合顺铂腔内注射治疗恶性胸腔积液的疗效和毒副反应.方法 2011年9月-2012年9月,将恶性胸腔积液患者60例,随机分为治疗组和对照组,每组各30例.在胸腔积液充分引流后,治疗组胸腔内注射三氧化二砷20 mg联合顺铂60 mg;对照组只给予胸腔灌注顺铂60 mg,胸腔灌注化学疗法药物两组均1次/周,共3次.观察疗效及不良反应.结果 治疗组和对照组的有效率分别为93.3%和56.7% (P<0.05).治疗组和对照组的一般状况改善率分别为70.0%和40.0% (P<0.05).两组的不良反应相近.结论 三氧化二砷联合顺铂腔内注射治疗恶性胸腔积液具有协同增效作用,不良反应小.

  12. Interventional Treatment Effects of Arsenic Trioxide for Advanced Primary Liver Cancer%三氧化二砷在中晚期原发性肝癌介入治疗方面的作用

    Institute of Scientific and Technical Information of China (English)

    侯毅斌; 刘琦; 段光峰; 萧慧菊; 王峻; 汤日杰

    2015-01-01

    Objective:To study the clinical effects and safety of arsenic trioxide for interventional treatment of advanced primary liver cancer. Method:126 patients with primary liver cancer in our hospital received the interventional treatment and randomly divided into two groups, 63 cases each group. The observation group were treated with arsenic trioxide and UFL; control group were treated with epirubicin and UFL. The treatment effect and adverse reactions of two groups were compared. Result: After interventional treatment , the total effective rate of observation group(74.6%) was significantly higher than that of control group(39.7%)(P<0.01); during treatment, the major adverse reactions were bone marrow suppression, nausea and vomiting, fever, pain, hepatic injury, etc. The symptoms were effectively relieved upon taking measures. Conclusion:The interventional treatment of arsenic trioxide for liver cancer can effectively and easily alleviate the patients’ pains, promote the clinical treatment and has fewer adverse reactions. It is worthy of clinical promotion.%目的:探讨三氧化二砷在中晚期原发性肝癌介入治疗中的临床效果。方法:选取我院收治的确诊为原发性肝癌的患者126例,均给予介入治疗。将其随机分成两组,每组63例。观察组患者治疗方案为三氧化二砷+超液态碘油;对照组患者治疗方案为表阿霉素(表柔比星)+超液态碘油。对比两组治疗效果以及不良反应发生情况。结果:126例肝癌患者给予药物介入治疗后,观察组总有效率为74.6%,对照组总有效率为39.7%,明显看出加入三氧化二砷介入治疗后,总有效率显著提高(P<0.01);治疗中主要出现的不良反应为骨髓抑制、恶心呕吐、发热、疼痛、肝功能损伤等,采取措施后可有效缓解。结论:三氧化二砷应用于肝癌介入治疗,有效减轻了患者的痛苦,改善了临床治疗效果,操作简单,不良反应少,值得临床推广。

  13. Silicon molybdenum blue spectrophotometric determination of silicon dioxide in arsenic trioxide%硅钼蓝分光光度法测定三氧化二砷中二氧化硅

    Institute of Scientific and Technical Information of China (English)

    谢辉; 赖心; 黄葡英

    2011-01-01

    In this study, hydrochloric acid was added into arsenic trioxide to remove arsenic by heating. The obtained residual was dissolved with sodium hydroxide. After acidification with nitric acid,silicon could form silicon molybdenum yellow complex with molybdate at pH 0. 9 using ammonium molybdate as color developer. With sulfuric acid increase the acidity, the complex was reduced to silicon molybdenum blue complex by ascorbic acid. The content of silicon dioxide was determined by spectrophotometry. The maximum absorption wavelength of silicon molybdenum blue complex was 813 nm. The relative standard deviations (RSD, n=6) were 1. 6 %-1. 9%. The determination results of this method were consistent with those obtained by ICP-AES.%研究了在三氧化二砷中加入盐酸,加热除砷,所得残渣用氢氧化钠溶解,硝酸酸化后,以钼酸铵为显色剂,在pH 0.9条件下,硅与钼酸盐形成硅钼黄络合物,用硫酸提高酸度,以抗坏血酸为还原剂,使硅形成稳定的硅钼蓝络合物,采用分光光度法测定其中的二氧化硅含量.硅钼蓝络合物最大吸收波长位于813 nm处.本法相对标准偏差(RSD)为1.6%~1.9%(n=6),测定结果与.ICP-AES法的结果相一致.

  14. As2O3联合Aspirin对诱导肝癌细胞凋亡的影响%Aspirin enhances arsenic trioxide-induced apoptosis of hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    郝立晓; 刘铁夫

    2012-01-01

    AIM: To investigate the effect of aspirin combined with arsenic trioxide (As2O3) on human hepatocarcinoma cell line Bel-7402 and to explore the possible mechanisms involved.METHODS: Cultured Bel-7402 cells were incubated with different concentrations of aspirin and As2O3, alone or in combination. After treatment, cell morphology was observed using an inverted microscope, cell proliferation was determined by MTT assay, cell apoptosis was measured by flow cytometry with annexin V/ propidium iodide staining, and cell cycle progression was analyzed by fluorescence-activated cell sorting.RESULTS: As2O3 and aspirin showed different degrees of inhibitory effect on the growth of Bel-7402 cells, and both were concentration-dependent. The two drugs had a synergistic effect, and the inhibitory effect in the combination group was more significant than those in the two monotherpay groups (both P < 0.05). Compared to treatment with 2.0 μmol/L As2O3 alone, treatment with 2.0 μmol/L As2O3 combined with 0.2 mmol/L aspirin significantly increased the apoptosis rate (5.64% ± 0.56% vs 7.35% ± 0.62%, P < 0.05), decreased the percentage of cells in G1 phase (0.52% ± 0.64% vs 32.03% ± 0.97%), and increased the percentages of cells in G2 phase or S phase (9.57% ± 0.82% vs 13.66% ± 0.82%, 50.41% ± 0.32% vs 54.37% ± 0.69%).CONCLUSION: Aspirin enhances As2O3-induced apoptosis of Bel-7402 cells possibly by altering cell cycle progression.%目的:观察As2O3与Aspirin联合应用对肝癌细胞Bel-7402的影响,并探讨其作用机制.方法:体外培养肝癌Bel-7402细胞,Aspirin、As2O3不同浓度孵育细胞.倒置显微镜观察细胞形态学改变,四甲基偶氮唑蓝(MTT)法检测As2O3和Aspirin单独及联合应用对Bel-7402细胞增殖情况的影响,流式细胞术观察细胞凋亡情况,并通过流式软件分析细胞周期变化.结果:As2O3及Aspirin对肝癌Bel-7402细胞生长均呈不同程度的抑制,且呈浓度依赖性.二者联合具有协同作用,药

  15. 维生素C对三氧化二砷抑制上皮性卵巢癌增殖的增敏效应研究%Role of Vitamin C as a sensitizer for arsenic trioxide in epithelial ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    高克非; 曾根

    2014-01-01

    Objective To investigate the role of Vitamin C as a sensitizer for arsenic trioxide in epithelial ovarian cancer cells and the apoptotic mechanisms. Methods In OVCAR-3 cells, the anti-cancer effects were ob-served when Vitamin C or AS2O3 was given alone, and the sensitizing effects of Vitamin C were observed when it was used in the combination with arsenic trioxide. MTT chemosensitivity test, Flow Cytometry for examination of apop-tosis and cell cycle status and Western-blot were applied. Results Dose-dependent antiproliferative effect on epi-thelial ovarian cancer cell lines was observed when Vitamin C or AS2O3 was applied as single agent, the IC50 value was 4.72μmol/L and 21.85μmol/L respectively. When the two agents were applied simultaneously, the growth inhibi-tion rate was significantly higher than that of the group treated with AS2O3 alone, and the P value of the two combined regimen experiments were 0.001, 0.012 respectively, the q value of the combined effects was 2.71, 1.63 respectively. These results showed synergistic effect of the two agents. Flow Cytometry testing showed significant S phase block and increased apoptosis rate in the combination treatment group. In Western-blot experiments, Bcl-2 expression of the combination treatment group was down-regulated,and Bax expression was up-regulated compared with the group treated by AS2O3 alone. Conclusion Vitamin C has sensitizing effect on arsenic trioxide in the treatment of epithelial ovarian cancer cell lines, which should be promising in the further study.%目的:观察维生素C对三氧化二砷(AS2O3)抑制上皮性卵巢癌细胞株的化疗增敏效应并探讨其凋亡蛋白相关机制。方法以上皮性卵巢癌细胞株OVCAR-3为研究对象,以噻唑蓝(MTT)药敏试验、流式细胞仪以及蛋白质印迹法检测维生素C对AS2O3化疗的增敏效应及其机制。结果 AS2O3和Vitamin C单药对上皮性卵巢癌细胞株均具有剂量依赖性的生长抑制作用,IC50

  16. 三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制%Effects and Mechanism of Arsenic Trioxide on Growth of Cervical Cancer in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    林晨; 拉莱·苏祖克; 史永华; 魏琴

    2011-01-01

    目的 研究三氧化二砷(arsenic trioxide,ATO,As2O3)对宫颈癌 HeLa 细胞裸鼠移植瘤生长的作用及机制.方法 建立裸鼠移植瘤模型,分为低浓度 As2 O3组[2mg/(kg·d)],高浓度As2O3 组[5mg/(kg·d)],顺铂(DDP)组[3mg/(kg·d)]及阴性对照组(0.9%氯化钠0.2ml/d),连续给药10d,观察抑瘤率及药物对裸鼠的影响.透射电子显微镜观察肿瘤的超微结构,免疫组织化学检测p-P38和Caspase-3的表达.结果 低浓度 As2 O3,高浓度 As2 O3及 DDP 的抑瘤率分别为22.95%、54.86%和54.48%,后两者的抑瘤率与阴性对照组的差异有统计学意义(P<0.05),但DDP的不良反应大.p-P38和 Caspase-3在As2 O3组的表达明显高于阴性对照组(P<0.05).结论 As2O3可通过诱导肿瘤细胞凋亡抑制宫颈癌移植瘤的生长.%Objective To explore the inhibitory effect of arsenic trioxide(ATO, As2O3 ) on the tumor growth of cervical cancer cell line HeLa subcutaneously implanted in nude mice and its mechanism.Methods Human cervical cancer xenografted model was established in nude mice. The tumor-bearing nude mice were randomly divided into the experimental groups: ATO low dose group [2mg/(kg ·d)], ATO high dose group [5mg/(kg · d)], DDP positive control group [3rng/(kg · d)], saline negative control group(0. 9%NaCl 0. 2ml/d). The drugs were administered intraperitoneally for 10 consecutive days. To observe the tumor inhibition rate and effects of drugs. Ultramicrostructure feature of tumor was observed under electron microscope. Immunohistochemistry was used to measure the expression of p-P38 and Caspase-3. Results Inhibited tumor volume of ATO low and high dose groups and DDP positive control group was 22. 95% ,54. 86% and 54. 48%, respectively. The inhibited effect of ATO 5mg/kg/d group was similar with DDP 3mg/kg/d group, but the toxic effect of DDP was higher than ATO. The expression of p-P38 and Caspase-3 was higher than negative control group (P <0. 05). Conclusion ATO can inhibit

  17. Study on the apoptosis of Raji cell line induced by arsenic trioxide and its correlation with Survivin gene%三氧化二砷诱导Raji细胞凋亡与Survivin基因关系的研究

    Institute of Scientific and Technical Information of China (English)

    Yi Long; Huimin Li; Chen Qing; Hua Liu; Yanli Zhang; Meijia Yu

    2008-01-01

    Objective:To investigate the apoptosis induction by arsenic trioxide (As2O3) in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene.Methods:After Raji cells were treated with As2O3 in different concentrations (1,2,4 and 8 μM),for 24,48 and 72 h,respectively,and cell proliferation was tested by MTT assay.Apoptosis was observed with electron microscope end DNA electrophoresis.The distribution of cell cycles and cell apoptosis were detected by flow cytometry.Expression of the Survivin gene was determined by real-time quantitative RT-PCR.Results:As2O3 (1-8 μM) inhibited Raji cells growth effectively in a dose- and time-dependent manner.As2O3 at 2-8μM could induce cell apoptosis and cell cycle arrest.However,As2O3 (1 μM) inhibited Raji proliferation only by cell cycle arrest,without any symptoms of cell apoptosis.At the same time,Survivin gene expression was down-regulated after the treatment.Conclusion:As2O3 could induce substantial proliferation inhibition,cell cycle arrest and apoptosis in Raji cell.Cell cycle arrest might be a reason why apoptosis occurs.As2O3 can markedly down-regulate expression of the Survivin gene in a dose- and timedependent manner.The down-regulated Survivin gene might be leading to cell apoptosis by As2O3.

  18. Assessment of the involvement of oxidative stress and Mitogen-Activated Protein Kinase signaling pathways in the cytotoxic effects of arsenic trioxide and its combination with sulindac or its metabolites: sulindac sulfide and sulindac sulfone on human leukemic cell lines.

    Science.gov (United States)

    Stępnik, M; Ferlińska, M; Smok-Pieniążek, A; Gradecka-Meesters, D; Arkusz, J; Stańczyk, M

    2012-06-01

    The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using L: -buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 μM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 μM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 μM) and DPI (0.0025-0.1 μM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

  19. 载三氧化二砷的PEG—PLGA隐性纳米粒的制备及体外研究%Preparation and in vitro Studies of Stealth PEGylated PLGA Nanoparticles as Carriers for Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    王志清; 刘卫; 徐辉碧; 杨祥良

    2007-01-01

    The aim of this study was to prepare arsenic trioxide (ATO)-loaded stealth PEGylated PLGA nanoparticles (PEG-PLGA-NPs) and to assess the merits of PEG-PLGA-NPs as drug carriers for ATO delivery. PEG-PLGA copolymer was synthesized with methoxypolyethyleneglycol (Mw=5000),D,L-lactide,and glycolide by the ring-opening polymerization method. Amorphous ATO was transformed into cubic crystal form to increase its solubility in the organic solvent. ATO-loaded PEG-PLGA-NPs were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method,and the main experimental factors influencing the characteristics of nanoparticles were investigated,to optimize the preparation. To confirm the escape of PEG-PLGA-NPs from phagocytosis by phagocytes,PEG-PLGA-NPs labeled rhodamine B uptake by murine peritoneal macrophages (MPM) were analyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were affected by the type and concentration of the emulsifiers,polymer concentration,and drug concentration. ATO-loaded PEG-PLGA-NPs,with particle size of 120.8nm,zeta potential of -10.73mV,encapsulation efficiency of 73.6%,and drug loading of 1.36%,were prepared under optimal conditions. The images of transmission electron microscopy (TEM) indicated that the optimized nanoparticles were near spherical and without aggregation or adhesion.The release experiments in vitro showed the ATO release from PEG-PLGA-NPs exhibited consequently sustained release for more than 26d,which was in accordance with Higuchi equation. The uptake of PEG-PLGA-NPs by MPM was found to decrease markedly compared to PLGA-NPs. The experimental results showed that PEG-PLGA-NPs were potential nano drug delivery carriers for ATO.

  20. Demethylation and alterations in the expression level of the cell cycle-related genes as possible mechanisms in arsenic trioxide-induced cell cycle arrest in human breast cancer cells.

    Science.gov (United States)

    Moghaddaskho, Farima; Eyvani, Haniyeh; Ghadami, Mohsen; Tavakkoly-Bazzaz, Javad; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

    2017-02-01

    Arsenic trioxide (As2O3) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As2O3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As2O3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns. To explore this, we examined promoter methylation status of 24 cell cycle genes in breast cancer cell lines and in a normal breast tissue sample by methylation-specific polymerase chain reaction and/or restriction enzyme-based methods. Gene expression level and cell cycle distribution were quantified by real-time polymerase chain reaction and flow cytometric analyses, respectively. Our methylation analysis indicates that only promoters of RBL1 (p107), RASSF1A, and cyclin D2 were aberrantly methylated in studied breast cancer cell lines. As2O3 induced CpG island demethylation in promoter regions of these genes and restores their expression correlated with DNA methyltransferase inhibition. As2O3 also induced alterations in messenger RNA expression of several cell cycle-related genes independent of demethylation. Flow cytometric analysis revealed that the cell cycle arrest induced by As2O3 varied depending on cell lines, MCF-7 at G1 phase and both MDA-MB-231 and MDA-MB-468 cells at G2/M phase. These changes at transcriptional level of the cell cycle genes by the molecular mechanisms dependent and independent of demethylation are likely to represent the mechanisms of cell cycle redistribution in breast cancer cells, in response to As2O3 treatment.

  1. Arsenic cardiotoxicity: An overview.

    Science.gov (United States)

    Alamolhodaei, Nafiseh Sadat; Shirani, Kobra; Karimi, Gholamreza

    2015-11-01

    Arsenic, a naturally ubiquitous element, is found in foods and environment. Cardiac dysfunction is one of the major causes of morbidity and mortality in the world. Arsenic exposure is associated with various cardiopathologic effects including ischemia, arrhythmia and heart failure. Possible mechanisms of arsenic cardiotoxicity include oxidative stress, DNA fragmentation, apoptosis and functional changes of ion channels. Several evidences have shown that mitochondrial disruption, caspase activation, MAPK signaling and p53 are the pathways for arsenic induced apoptosis. Arsenic trioxide is an effective and potent antitumor agent used in patients with acute promyelocytic leukemia and produces dramatic remissions. As2O3 administration has major limitations such as T wave changes, QT prolongation and sudden death in humans. In this review, we discuss the underlying pathobiology of arsenic cardiotoxicity and provide information about cardiac health effects associated with some medicinal plants in arsenic toxicity.

  2. 三氧化二砷体外对哮喘患者外周血T细胞凋亡和白细胞介素4分泌的影响%Effects of arsenic trioxide on apoptosis and interleukin-4 release of peripheral T cells from asthmatic patients in vitro

    Institute of Scientific and Technical Information of China (English)

    覃冬云; 黄韧; 吴铁

    2007-01-01

    目的 探讨三氧化二砷治疗哮喘的可能机制.方法 分离21例哮喘患者和20例健康对照者外周血T 细胞,分别加入三氧化二砷(0.1 mg·L-1)或地塞米松(5 mg·L-1)培养24 h.用ELISA方法检测培养上清液中白细胞介素4(IL-4)的含量,用荧光显微镜、流式细胞术和细胞色素c 试剂盒检测细胞凋亡.结果 哮喘患者T细胞自发释放IL-4较健康对照者明显增多;三氧化二砷对健康对照者T细胞IL-4的释放无影响,对哮喘患者T细胞IL-4释放增加具有抑制作用;地塞米松可使两组T细胞IL-4的释放明显降低.哮喘患者外周血T细胞体外培养24 h凋亡百分率较健康对照者明显降低,细胞浆细胞色素c含量降低;三氧化二砷明显增加哮喘患者T细胞凋亡的百分率和细胞色素c的含量,对健康对照者作用不明显;地塞米松可使两组的T细胞凋亡百分率和细胞色素c含量增加.结论 三氧化二砷治疗哮喘的机制可能与诱导哮喘患者T细胞凋亡和IL-4分泌减少有关.%AIM To study the possible mechanism of the treatment of arsenic trioxide on asthma. METHODS T cells isolated from 21 asthmatic patients and 20 healthy controls were treated with arsenic trioxide (0.1 mg·L-1) or dexamethasone (5 mg·L-1),in vitro, for 24 h. Interleukin-4 (IL-4) levels in supernatants from T cells were quantified with ELISA. Cell apoptosis was measured by using fluorescence microscopy, flow cytometry and cytochrome c ELISA kit. RESULTS T cells of asthmatic patients spontaneously released more IL-4 than that of healthy controls. Arsenic trioxide significantly decreased IL-4 release of T cells from asthmatic patients, which was more obvious compared with healthy controls. Dexamethasone decreased IL-4 release in both groups. Apoptosis percentage and cytochrome c content in cytoplasm of T cells from asthmatic patients were lower than those from healthy controls. Arsenic trioxide significantly increased the apoptosis percentage and

  3. Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo

    Science.gov (United States)

    Atashrazm, Farzaneh; Lowenthal, Ray M.; Dickinson, Joanne L.; Holloway, Adele F.; Woods, Gregory M.

    2016-01-01

    The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies. When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL. In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients. Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL. PMID:27329592

  4. Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo.

    Science.gov (United States)

    Atashrazm, Farzaneh; Lowenthal, Ray M; Dickinson, Joanne L; Holloway, Adele F; Woods, Gregory M

    2016-07-19

    The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies.When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL.In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients.Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL.

  5. 三氧化二砷治疗血液病后合并带状疱疹的临床研究%Clinical analysis of hematologic disorders complicated with herpes zoster after treating with arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    张旗; 慕俐君; 王晓波; 李莉; 康志杰; 闫金松

    2011-01-01

    Objective To explore the increasing risk of herpes zoster and its possible mechanisms for hematologic disorders treated with arsenic trioxide (ATO). Methods The cases were divided into study group (with ATO) and control group (without ATO). The incidence rate of herpes zoster was compared between the two groups, and then the average cycles of chemotherapy were compared between the patients complicated with herpes zoster or not in study group. Results The rate of herpes zoster was significantly higher in study group than that in control group (χ2 =4.492, P =0.034). The rates of herpes zoster were 23.95 % (23/96) in study group and 7.89 % (3/38) in control groups. Patients in study group with herpes zoster had received 7.60 cycles and those without herpes zoster 7.72 cycles of chemotherapy on average (Z=0.976, P=0.296).Conclusion The risk of herpes zoster complication in hematologic disorders was increased after ATO treatment which probably activated varicella-zoster virus.%目的 分析三氧化二砷(ATO)治疗血液病后合并带状疱疹感染患者的临床特征及其可能的发生机制.方法 将研究对象分为研究组(应用ATO)和对照组(未应用ATO),观察两组带状疱疹发病率,以及研究组中发生带状疱疹和未发生带状疱疹患者的平均化疗次数.结果 研究组带状疱疹发病率为23.95%(23/96),发生带状疱疹者平均化疗7.60次,未发生带状疱疹者平均化疗7.72次(Z=0.976,P=0.296);对照组带状疱疹发病率7.89%(3/38),两组间带状疱疹发病率差异有统计学意义(χ2=4.492,P=0.034).结论 ATO治疗血液疾病可以增加带状疱疹的发病率,可能与其激活水痘-带状疱疹病毒有关.

  6. Term Effect of Arsenic Trioxide Treatment of Advanced Hepatocellular Carcinoma%三氧化二砷治疗中晚期原发性肝癌的近期疗效

    Institute of Scientific and Technical Information of China (English)

    林志宇; 马闻; 付榆; 乔青; 宿向东

    2014-01-01

    Objective To study the clinical therapeutic effects and the side effects of arsenic trioxide(As2O3)when used to treat middle or advanced primary hepatocellular carcinoma by interventional ways. Methods 33 cases with single agent arsenic trioxide 10 mg/d and saline infusion for 14 d for 1 cycles, 2 weeks intermittent, at least 2 cycles. Results All the 4 patients with PR, 22 cases of NC, 7 cases of PD, the efifciency of 12%. Clinical beneift rate:78.8%;pain relief rate was 82.7%, the quality of life of patients with 81.8% increase; adverse reaction of the treatment mainly Ⅰ to Ⅱ gastrointestinal reaction and hematologic toxicity, liver function impairment mild. Conclusion Arsenic trioxide in the treatment of middle or advanced primary hepatocellular carcinoma have the good curative effect, less adverse reaction, is a good choice for l hepatocellular carcinoma treatment, worthy of clinical application.%目的:观察三氧化二砷治疗中晚期原发性肝癌的近期疗效及不良反应。方法对33例采用单药三氧化二砷10mg/d加入生理盐水静脉滴注连续14d为1个周期,间歇2周,至少使用2个周期。结果全组4例PR,22例NC,7例PD,客观有效率12%。临床受益率:78.8%;疼痛缓解率为82.7%,81.8%患者生存质量提高;该治疗方案不良反应主要表现为Ⅰ~Ⅱ度胃肠道反应和血液学毒性,轻度的肝功能损害。结论三氧化二砷治疗中晚期原发性肝癌有较好疗效,不良反应较小,是肝癌治疗用药的较佳选择,值得临床推广。

  7. 三氧化二砷在系统性红斑狼疮治疗中的应用%The application of arsenic trioxide in the treatment of systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    康俞莉; 章强强

    2013-01-01

    As an autoimmune disease, systemic lupus crythematosus is caused by genetics, environment, immune factors, etc, which results in multi-organs and multi-system's damage. It has complex pathogenesis, diverse clinical manifestations and the progress conditions ongoing deteriorated. Traditionally, combining glucocorticoid with immunosuppressant is the main treatment for systemic lupus erythematosus, while cytotoxic drugs or biological modifiers are supplemented for severe patients, but the result is not satisfactory, and these drugs often lead to tremendous side effects. In recent years, a large number of basic and clinical trials in domestic and abroad indicate that immune factors play a important role in the pathogenesis of SLE. Arsenic trioxide (ATO) can effectively alleviate and control the symptoms of SLE, what's more, many in-depth research have attempted to figure out the mechanism of ATO to the treatment of SLE. This review intends to make a brief introduction of pharmacodynamic characteristics of ATO as well as its clinical application, and mechanism of ATO in the treatment of SLE.%系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种由遗传、环境、免疫等多种因素参与引起的多器官、多系统损害的自身免疫性疾病,其发病机制复杂,临床表现多样,病情多呈进行性发展.对于SLE的治疗,传统上主要以精皮质激素联合免疫抑制剂为主,严重者辅以细胞毒药物或生物调节剂,但总体疗效欠佳,且不良反应较大.近年来,大量的基础研究和临床试验表明,免疫因素在SLE发病机制中起主要作用, 三氧化二砷(ATO)能有效缓解、控制SLE的症状,并且对ATO治疗SLE的作用机制也进行了许多深入的研究.该文拟从ATO的药效特性、临床应用、作用机制等方面对ATO治疗SLE的研究现况做一概述.

  8. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

    Science.gov (United States)

    Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

    2017-02-20

    Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10(9)/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

  9. 三氧化二砷联合华蟾素治疗晚期肝癌的近期疗效分析%Arsenic trioxide joint element HuaChan recent curative effect analysis for the treatment of advanced liver cancer

    Institute of Scientific and Technical Information of China (English)

    毛雪梅

    2014-01-01

    Objective:To observe the analysis of arsenic trioxide in late in the treatment of liver cancer coalition HuaChan short-term curative ef ect.Methods:A retrospective analysis of clinical data of 56 patients with advanced liver cancer,according to the treatment time is divided into research group (28 cases)and control group (28 cases),two groups of patients were given conventional treatment,the team on the basis of the joint HuaChan element arsenic trioxide,two groups of patients in the near future curative ef ect observed.Result:The team objective ef iciently,clinical benefit rate and life quality imG provement were superior to control group,with statistical significance dif erence (P<0.05).Conclusion:On the basis of routine therapy for patients with advanced liver cancer arsenic trioxide joint HuaChan hormone treatment,can achieve good short-term curative ef ect,can ef ectively improve the clinical symptoms and quality of life,resistant to certain toxicity.%目的:观察分析在晚期肝癌治疗中三氧化二砷联合华蟾素的近期疗效.方法:回顾性分析56例晚期肝癌患者临床资料,按治疗时间分为研究组(28例)和对照组(28例),两组患者均给予常规治疗,研究组在此基础上加以三氧化二砷联合华蟾素,对比观察两组患者近期疗效.结果:研究组客观有效率、临床受益率、生活质量改善均优于对照组,具有统计学差异意义(P<0.05).结论:结论在常规治疗基础上给予晚期肝癌患者三氧化二砷联合华蟾素治疗,可取得良好的近期疗效,能有效改善患者临床症状和生活质量,可耐一定毒性.

  10. Construction of subtractive cDNA Library of apoptosis-related genes in NB4 cells treated by arsenic trioxide%用抑制性差减杂交构建As_2O_3诱导的NB4细胞凋亡相关基因文库

    Institute of Scientific and Technical Information of China (English)

    狄春红; 顾少华; 谭晓华; 仙玲玲; 吴奇涵; 杨磊

    2009-01-01

    Objective: Construct the gene library of apoptosis related genes in acute promyelocytic leukemia (APL) cell line NB4 cells treated by arsenic trioxide to clarify the apoptotic mechanism of NB4 cells. Method: APL cell line NB4 cells treated with or without arsenic trioxide for 24 hours. Total RNA was extracted and suppress subtractive hybridization (SSH) was conducted according to the manual. With the cDNA of the apoptosis cells as the tester and that of control cells as the driver, forward and reverse hybridization was performed- Differentially expressed genes were linked with pGEM-Teasy cloning vector and transformed into E.coli DH5α. The positive clones were screened by blue and white spot. PCR were used to amplify these genes. Result: The subtractive cDNA libraries related with apoptosis of NB4 cells were successfully constructed. Conclusion: The constructed subtractive libraries are suitable for further study on the functional genes associated with apoptosis of NB4 cells induced by arsenic trioxide.%目的: 构建三氧化二砷(As_2O_3)诱导的急性早幼粒细胞白血病细胞株NB4细胞凋亡相关基因文库.方法:用含4 μmol·L~(-1)As_2O_3和正常培养基培养NB4细胞24 h,抽提总RNA,经逆转录酶合成双链cDNA,分别以砷诱导凋亡组和对照组作为tester和driver,进行双向抑制性差减杂交(supptess-ion sublxactive hybridization,SSH),筛选As_2O_3诱导的NB4细胞凋亡相关基因,将差异表达基因进行PCR扩增并与pGEM-Teasy克隆载体连接,转化DH5 α大肠杆菌,经蓝白斑筛选获得白色阳性克隆,PCR扩增出未知基因片段.结果:成功构建了分别代表在NB4细胞中表达上调和下调的基因文库.结论: 经双向抑制性差减杂交获得了NB4细胞差异表达基因文库,为克隆NB4细胞凋亡相关基因奠定了基础.

  11. 三氧化二砷对人子宫内膜癌移植瘤的影响%EFFECTS OF ARSENIC TRIOXIDE ON HUMAN ENDOMETRIAL CANCER XENOGRAFT

    Institute of Scientific and Technical Information of China (English)

    胡美丽; 李利; 王晓玲; 康山

    2014-01-01

    目的:探讨三氧化二砷(aresenic trioxide,AS2 O3)对裸鼠荷人子宫内膜癌皮下移植瘤的生长抑制作用及作用机制。方法建立裸鼠荷人子宫内膜癌 HEC-1-A 细胞移植瘤动物模型,随机分为5组,A 组(AS2 O34mg· kg-1·d-1)、B 组(AS2 O36mg·kg-1·d-1)、C 组(AS2 O38mg·kg-1·d-1)、D 组(顺铂3mg·kg-1·d-1)、阴性对照 E 组(生理盐水组),腹腔连续给药14d,计算瘤体积和瘤质量抑制率,观察用药前后裸鼠体质量改变。结果A、B、C、D 组肿瘤体积抑制率分别为50.97%、75.58%、56.92%、52.23%,肿瘤质量抑制率分别为10.15%、29.33%、16.67%、14.69%,与 E 组比较差异均有统计学意义(P <0.05)。用药前后 AS2 O3各组体质量变化不明显,而 D 组裸鼠体质量变化差异有统计学意义。结论 AS2 O3对鼠荷人子宫内膜癌移植瘤的生长有抑制作用,且治疗剂量的AS2 O3对子宫内膜癌异种移植瘤的抑制作用强于顺铂,而不良反应弱,因此 AS2 O3有希望成为一种新型的子宫内膜癌治疗药物。%Objective To explore the inhibitory effect of arsenic troixide(AS2 O 3 )on the growth of nude mice bearing human endometrial carcinoma transplanted subcutaneously and its mechanisms.Methods Human endometrial cancer xenograft models were established in nude mice using HEC-1-A cell,then were divided into five groups as following,group A(AS2 O 3 4mg· kg-1 ·d-1 ),group B(AS2 O3 6mg· kg-1 · d-1 ),group C(AS2 O 3 8mg· kg-1 · d-1 ),group D (cisplatin 3mg·kg-1 ·d-1 ),and group E(saline group).The drugs were given intraperitoneally for 14 d,then the inhibition rate of tumor volume and tumor mass were calculated.The change of body mass of nude mice after treatment was measured.Results The tumor volume was inhibited by 50.97%,75.58%,56.92%,52.23%,and the tumor mass was inhibited by 10.15%,29.33%, 16.67%,14.69%,respectively,in group A,group B

  12. Influence of arsenic trioxide on the growth activity and apoptosis of gastric cancer cell during hypoxia%三氧化二砷对低氧下人胃癌细胞SGC-7901生长活性及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    王彬; 王树庆

    2009-01-01

    目的 探讨三氧化二砷(As2O3)在低氧条件下对体外培养的人胃癌细胞SGC-7901生长的抑制及凋亡影响.方法 用氯化钴(CoCl2)制作低氧模型, 设常氧组、低氧组、低氧加药物组,分别取0.5、1.0、2.0、5.0、10.0 μmol/L五个不同浓度的As2O3作用于胃癌细胞,用细胞活力测定(MTT)法检测药物作用后的细胞活力,HOECHST33258染色试剂盒测细胞凋亡.结果 ①低氧加药物组As2O3对SGC-7901 细胞生长有抑制作用,与常氧对照组比较差异有统计学意义(P<0.05),并呈剂量-时间-效应关系.②低氧加药物组中,随着As2O3浓度的升高,胃癌细胞凋亡率也逐渐升高(P<0.05).结论 低氧下As2O3对人胃癌细胞SGC-7901生长有抑制和诱导凋亡作用,这种作用可能是As2O3发挥抗肿瘤的生物学基础.%Objective To investigate the effect of arsenic trioxide (As2O3) on the inhibition and apoptosis of gastric cancer cell SGC-7901 during hypoxia. Methods The environment of hypoxia was established by CoCl2 method. The gastric cancer cell were divided into three groups:normal group, hypoxia group and hypoxia combined arsenic trioxide group. The gastric cancer cell SGC-7901was stimulated respectivly 0.5,1.0,2.0,5.0 μmol/L and 10.0 μmol/L of arsenic trioxide.The growth activity of the gastric caner cell of As2O3 was determined by MTT ,and the apoptosis of the gastric caner cell by arsenict rioxide were examined with HOECHST33258 of gastric cancer cell SGC-7901, there was a significant difference rate gradually increased with higher concentration of As2O3 in hypoxia combined arsenic trioxide groups(P<0.05). Conclusion The growth of human gastric cancer cell SGC-7901 were suppressed, and apoptosis of human gastric cancer cell SGC-7901were induced by As2O3 during hypoxia,it may be biological basic of anti-tumor of As2O3.

  13. Anti-tumor Effects and Mechanism of Arsenic Trioxide in Combination with Sodium Citrate in Gastric Cancer Cells in vitro%柠檬酸钠联合三氧化二砷体外抗人胃癌细胞及其作用机制

    Institute of Scientific and Technical Information of China (English)

    郑步平; 张晓东; 陆云飞

    2012-01-01

    Objective To study the anti-tumor effects of citrate combined with arsenic trioxide on human gastric cancer cell in vitro and possible mechanism. Methods Citrate (final concentration of 5 mmol / L) and (or) different concentrations of As2O3 (final concentration was 5 or 10 μmol / L) treated in vitro cultured gastric cancer cell line SGC-7901 and BGC-803. Flow cytometry was used to detect apoptosis and cell cycle changes. The apoptosisrelated gene Bcl-2 and Mcl-1 expressions were identified by RT-PCR to observe. Results Citrate combining with As2 O3 had a stronger inhibition function on human gastric cancer cell line compared with citrate or As2O3 (P<0. 05) alone. Compared with blank group, the cell cycle distribution was arrested at G2/ M phase, and the proportion of G0/G1 phase cell decreased and G2/M phase increased (P<0. 05). The expression of bcl-2 and mcl-1 was significantly decreased(P<0. 05). Conclusion Citrate combining with As2O3 had the synergistic effects on gastric cancer cell. The mechanism might be related to cell cycle blocking and apoptosis-inducing effects through bcl-2 and mcl-1 genes.%目的 探讨柠檬酸钠(Citrate)与三氧化二砷(As2O3)联合应用对胃癌细胞的凋亡及其作用机制.方法 用Citrate(终浓度为5 mmol/L)和(或)不同浓度的As2O3(终浓度依次为5、10 μmol/L)处理体外传代培养的胃癌细胞株SGC-7901和BGC-803.流式细胞仪检测细胞凋亡和细胞周期的变化;RTPCR法观察凋亡相关基因Bcl-2、Mcl-1表达的变化.结果 Citrate与As2O3联合应用相对于单用Citrate或As2O3可显著提高诱导胃癌细胞凋亡率(P<0.05);与空白组相比,用药后G0/G1期细胞比例下降,G2/M期细胞比例上升,细胞周期阻滞于G2/M期,抗凋亡基因Bcl-2、Mcl-1表达明显下降.结论 Citrate与As2O3联合应用具有协同抗胃癌细胞的作用,其机制可能与细胞周期阻滞、增强诱导胃癌细胞凋亡以及调控凋亡相关基因的表达有关.

  14. Arsenic trioxide enhances the therapeutic efficacy of adjuvant post-operative chemotherapy of gastric carcinoma while protecting bone marrow%三氧化二砷改善胃癌患者术后辅助化疗疗效同时减轻骨髓抑制

    Institute of Scientific and Technical Information of China (English)

    Hong Sui; Yuxian Bai; Yu Han; Kaibing Wang

    2009-01-01

    Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.

  15. 三氧化二砷联合华蟾素抗裸鼠人肝癌移植瘤血管新生的作用%Anti-angiogenesis Effect of Arsenic Trioxide plus Cinobufacin on Human Hepatocarcinoma Transplantation Model Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘琳; 陈宝安; 秦叔逵; 赵伟; 李苏宜; 邱少敏; 王南瑶

    2011-01-01

    Objective To study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well. Methods Human hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2. 5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor(EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope ( TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.Results The tumor weight and volume were 0. 65 ± 0. 25 g and 0. 44 ± 0. 14 cm3 in GB, 0. 70 ± 0. 27 g and 0. 46 ±0. 19 cm3 in GC, 0.42 ±0. 16 g and 0. 26 ±0. 11 cm3 in GD, all significantly lower than those in GA (1.06 ±0. 25 g and 0. 67 ±0. 17 cm3, P<0. 05). The coefficient of drug interaction (CDI) on tumor weight was 0. 97 and that on tumor size was 0. 86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed. Conclusions As2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the

  16. The curative effect with the combination therapy of Arsenic Trioxide and Ascorbic Acid in relapsed and refractory multiple myeloma%亚砷酸联合维生素C治疗复发难治性多发性骨髓瘤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王祥民; 张姣丽; 季国; 石培民

    2014-01-01

    Objective To investigate the curative effect with the combination therapy of Arsenic Trioxide and Ascorbic Acid in relapsed and refractory multiple myeloma. Methods 42 patients of relapsed and refractory multiple myeloma hospitalized during 2008 and 2011 were enrolled, and randomly divided into two groups: arsenic trioxide intervention group(control group)and arsenic trioxide combine with ascorbic acid intervention group(combination group), with each group 21 patients. The control group were given arsenic trioxide 10 mg/d intrave-nously daily. Each cycle was 6 weeks in duration, comprising 4 weeks of therapy followed by 2 weeks of intermission;while the combination group received ascorbic acid 1.0 g/d intravenously daily during the treatment time of arsenic trioxide in addition to the treatment of the control group. All patients received thalidomide 100 mg/d orally during the treatment intermission. Results (1) The combination group's overall response was 63%, which was much higher than the control group(29%)(P=0.043). (2) Kaplan-Meier statistical analysis showed that the median progression-free survival of the combination group was 9.0 months(range 6.2-11.8 months), which was longer than the control group(P=0.043). The median overall survival of the combination group was 14.0 months(range 11.4-16.6 months), which was also longer than the control group(P=0.038). (3) No significant difference was found between the two groups when referred to the adverse events(P>0.05). Conclusion Compared with the control group, the combination therapy of arsenic Trioxide and ascorbic acid acquired better curative effect in relapsed and refractory multiple myeloma patients.%目的:探讨亚砷酸联合维生素 C 对复发难治性多发性骨髓瘤的疗效,并与单用亚砷酸治疗进行比较。方法将2008至2011年收治的42例复发难治性多发性骨髓瘤患者随机分为两组:单用亚砷酸组(对照组)、亚砷酸联合维生素 C 组

  17. Efficacy of Arsenic Trioxide combined with GDP regimen for patients with aggressive relapsed or refractory non-Hodgkin's lymphoma%亚砷酸联合GDP方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    丁富强; 乔红梅; 李晓霞; 李恩孝

    2011-01-01

    目的:观察亚砷酸(三氧化二砷,As2O3)联合GDP方案(吉西他滨,顺铂,地塞米松)治疗难治性或复发性非霍奇金淋巴瘤(non-hodgkin's lymphoma,NHL)的有效率.方法:23例难治性或复发性非霍奇金淋巴瘤(NHL),给予吉西他滨1000mg/m2,第1和第8天,顺铂25mg/m2 第1-3天,地塞米松 20mg/m2,第1-5天,As2O310mg/d,第1-14天.21天为1个周期.结果:完全缓解9例,部分缓解6例,总有效率65.22%.肿瘤中位进展时间6个月,1年生存率39.13%.不良反应主要为血液学毒性.结论:亚砷酸联合GDP方案是治疗难治性或复发性非霍奇金淋巴瘤较为安全有效的化疗方案.%Objective:To evaluate the efficacy and safety of chemotherapy regimen with arsenic trioxide ( As2 O3 )combined with GDP ( gemcitabine, cisplatin and dexamethasone ) for patients with aggressive relapsed or refractory NHL. Methods: All 23 patients with relapsed or refractory NHL were observed,23 patients were treated by gemcitabine 1000 mg/m2 on d1 ,8, cisplatin 25 mg/m2 on d1-3 and dexamethasone 25 mg/m2 on d1-5, Arsenic oxide 10mg/d on d1-14。 21 days for a cycle. Results: Of experimental group all response rate was 65.22% ,including 9 complete response and 6 partial response. Median time to progression was 6 months, and 1 year survival rate was 39.13%.The major adverse reaction was toxicity of bone marrow. Conclusion: Arsenic trioxide combined with GDP regimen is effective and safe for patients with aggressive relapsed or refractory non - Hodgkin's lymphoma.

  18. Prevention of posterior capsule opacification by combination of arsenic trioxide and perfect capsule%密闭囊袋冲洗系统模拟抑制人晶状体上皮细胞的研究

    Institute of Scientific and Technical Information of China (English)

    张红; 王立新; 于旭辉; 高维奇; 刘平

    2010-01-01

    Despite recent improvements in IOL design, posterior capsule opacification (PCO)remains a significant clinical problem after cataract surgery. The Perfect Capsule device ( Milvella, Ltd. ,Epping, Australia) permits the introduction and subsequent removal of potentially toxic agents into the closed capsular bag. The present purpose was to detect the effectiveness of arsenic trioxide ( As2O3 ) to cultured human lens cells and cells within the human capsular bag. Methods All experiments were carried out with 2 minutes exposure to As2O3. Effect of As2O3 on FHL124 cells growth was tested by MTT. Changes in cell calcium levels induced by high concentration of As2O3 were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation. In vitro human capsular bags were also tested after a sham surgery was performed using the Perfect Capsule device to form a closed system. As2O3 (10、30、100、300、1000 μmol/L ) were used with donor match-pairs treated with medium alone. (n =3 in all cases). Ongoing observations were by phase-contrast microscopy. Cellular architecture was examined by fluorescence cytochemistry. Results As2O3 of 100 μmol/L and above inhibited the growth of FHL 124 cells in a dosedependent manner with 2 minutes exposure( t = 5. 217, P < 0. 01, IC5o is 130 μmol/L)As2O3 depleted the%目的 利用密闭囊袋冲洗系统和人后发性白内障(PCO)囊袋模型,研究三氧化二砷(As2O3)在短时间内对PCO的防治作用.方法 实验研究.严格将时间控制在2 min时,在细胞培养条件下,四甲基偶氮唑盐比色法观察As2O3对人晶状体上皮细胞(LEC)系FHL124细胞的抑制作用;乳酸脱氢酶释放实验观察As2O3对FHL124细胞的损伤作用;荧光显微镜动态检测细胞内Ca2+浓度的变化.建立人PCO囊袋模型,应用密闭囊袋冲洗系统观察As2O3对原代人LEC的作用.浓度反应曲线用Hill公式求IC50值.所有实验数据结果用均数

  19. 三氧化二砷诱导人晶状体上皮细胞凋亡的机制研究%Mechanism of arsenic trioxide induced apoptosis in cultured human lens epithelium cells

    Institute of Scientific and Technical Information of China (English)

    张红; 刘平; 于旭辉; 宋甄

    2008-01-01

    Objective To study cytotoxic effects of arsenic trioxide(As2O3)on the human lens epithelium cells and to identify the bioiogical mechanism for these effects.Methods In this experimental study,human lens epithelium cells(FHL124 cells)were cultured in Eagle's minimum essential medium supplemented with 5%fetal calf serum.The effects of As2O3 on FHL124 cells growth were tested by MTT,and apoptosis was detected by TUNEL assay.Gene changes were detected by real-time PCR(Taqman).As2O3-induced changes in cell calcium level were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation.Results As2O3 inhibited the growth of FHL 124 cells in vitro in a dose-dependent manner,given an IC50 value of 1.5 μmol/L As2O3 induced apeptosis of FHL124 cells as showed by TUNEL assay.As2O3 provoked an endoplasmic reticulum(ER)stress response identified through an up regulation of EIF2A,ERN1 and ATF6(F=8.51,P=0.0005).As2O3 depleted the calcium store and consequently lead to a decrease of calcium signaling(P=0.0018).Moreover,As2O3 had a modcrate effect on the caicium influx pathway.Conclusions As2O3 inhibits the growth and induces apoptosis of human lens epithelium cells.As2O3 provokes an ER stress which could be the cause of apoptic processes.%目的 研究三氧化二砷(As2O3)对离体培养的人晶状体上皮细胞(FHL124)的凋亡及其作用机制.方法 实验研究.四甲基偶氮唑盐比色法观察As2O3对FHL124细胞的抑制作用;原位缺口末端标记(TUNEL)法测定细胞凋亡;Taqman实时荧光定量PCR检测基因表达的变化;荧光显微镜动态监测细胞内Ca2+浓度的变化.As2O3对FHL124细胞的生长抑制和细胞内Ca2+浓度的变化采用t检验进行分析;3种基因不同处理组间表达水平差异的比较采用Wilks'λ检验;单个基因比较采用LSD-t检验.结果 As2O3(3×10-7~1×10-4mol/L)对FHL124细胞的作用呈浓度依赖性,1 μmol/L As2O3即可显著抑制FHL124细

  20. 三氧化二砷逆转人胃癌细胞SGC7901/ADR耐药性的作用机制%Reversal mechanism of arsenic trioxide in the drug resistance of human gastric cancer cell line SGC7901/ADR

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the reversal effect of arsenic trioxide (As2O3) on the multidrug resistance of human gastric tumor SGC7901/ADR cell line to adriamycin (ADM) and its reversal mechanisms. Methods: The non-cytotoxic concentration of As2O3 and the sensitivity of SGC7901/ADR cells to ADM were detected by MTT assay. The drug concentration and P-gp function of SGC7901/ADR cells were measured with flow cytometry (FCM), and the impacts of As2O3 on the GST-π and TopoⅡ expressions of SGC7901/ADR cells were analyzed by immunohistochemical method. Results: As2O3 at 0.4 to 0.8 μmol/Lconcentrations were not significantly cytotoxic to SGC7901/ADR cells. As2O3 at 0.8 μmol/L could improve the sensitivity of SGC7901/ADR cells to ADM via inhibiting P-gp function, down-regulating GST-π expression and increasing the intracellular accumulation of ADM in SGC7901/ADR cells. Conclusion: As2O3 can reverse partly the drug-resistance of SGC7901/ADR cells to ADM, which may be related with inhibiting the P-gp function and down-regulating GST-π expression.

  1. 三氧化二砷诱导人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的细胞分化和凋亡的研究%Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    郑毓武; ZHENG Yuwu; 杜彩文; DU Caiwen; 李德锐; LI Derui; LIN Yingcheng; WU Mingyao

    2004-01-01

    Objective: To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1ceils were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As2O3 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As2O3 treatment group when compared with control group. Conclusion: As2O3 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  2. 亚砷酸逆转多药耐药相关蛋白的作用研究%Effects of the concentrations of glutathione and the related mechanisms of arsenic trioxide (As2 O3) on Multidrug Resist-ance-associated Pr otein

    Institute of Scientific and Technical Information of China (English)

    王涛; 马梁明; 张华屏; 牛燕燕; 任瑞瑞

    2014-01-01

    Objective To investigate the apoptosis-inducing effect , inhibiting MRP-1 and mRNA expression of arsenic trioxide (As2O3) and buthionine sulfoximine (BSO) on multidrug-resistant cell-K562A/DM cell .To compare the effect of As2O3 and the com-bined group .To determine the effect of intracellular GSH content on the arsenic effect .Methods To investigate the effect of the arse-nic group (0.5,2.0,5.0μmol/L)and/or BSO (100μmol/L) on multidrug-resistant cell -K562/ADM cell.To detect the change of the correlated index .⑴Intracellular GSH contents were measured using Glutathione Assay Kit by spectrophotometry .⑵MRP-1 expression were determined by flow cytometry .⑶MRP-1 mRNA expression were directed by semi-quantitative RT-PCR.Results After the GSH contents were degraded by the combination of clinic dose arsenic group (0.5,2μmol/L) and BSO(100μmol/L), in 48 hours and 72 hours, the effect of the combination group ( clinic dose arsenic group ) was obviously stronger than the clinic dose arsenic group and the high dose arsenic group .In 48 hours, the MRP-1 mRNA depressive effect of the combination group ( clinic dose arsenic group ) was obviously stronger than high dose arsenic group .In 72 hours, the MRP-1 depressive effect of the combination group ( clinic dose arsenic group ) was obviously stronger than high dose arsenic group .Conclusions The intracellular GSH contents closely correlated with the arsenic effect .The combination of clinic dose arsenic and BSO inhibit obviously MRP-1 expression and MRP-1 mRNA expres-sion in K562/ADM cell.%目的:研究γ-谷氨酰半胱氨酸合成酶抑制剂-丁硫氨酸亚砜胺(buthioninesulfoximine,BSO)联合亚砷酸(As2O3)对肿瘤多药耐药细胞-K562/ADM细胞中多药耐药相关蛋白1(MRP1)和其编码基因mRNA的抑制作用,比较单用亚砷酸与两药联合的作用效果,探讨降低谷胱甘肽( Glutathione,GSH)含量后对亚砷酸( As2 O3)逆转耐药作用效果的

  3. Study on the inhibitory effects and related toxicity of all-trans-retinoic acid combined with arsenic trioxide on transplanted tumor of human bladder neoplasms in nude mice%全反式维甲酸联合三氧化二砷抗膀胱癌作用及其毒副作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    周振玉; 张永; 陈家存

    2011-01-01

    目的 观察全反式维甲酸(ATRA)联合三氧化二砷(As2 O3)对膀胱癌细胞株BIU-87裸鼠移植瘤生长的抑制作用,及其毒副作用。方法建立人膀胱癌裸鼠皮下移植瘤模型40只,随机等分为4组:对照组,ATRA组,As2 O3组,ATRA和As2O3联合用药组;裸鼠瘤体内连续注射用药14d。停药后48 h检测血常规和肝、肾功能;处死裸鼠,测量移植瘤体积、重量,计算抑瘤率;移植瘤及心、肝、肾等组织HE染色,观察其病理变化;瘤组织免疫组化S-P法检测血管内皮生长因子(VEGF)表达、CD43标记的微血管密度MVD的表达。结果与对照组比较,As2 O3组及ATRA组移植瘤生长明显受到抑制(质量抑瘤率分别为43.77%,41.82%),两者联合用药后,抑制作用显著增强(质量抑瘤率为68.55%),抑瘤率差异具有统计学意义(x2 =26.81,P<0.01);As2O3组、ATRA组、联合用药组均不同程度下调VEGF表达(OD值分别为27.33±2.17,20.72±2.01,19.23±2.32,17.16±1.59)及MVD的表达(OD值分别为141.12±8.38,43.39±7.41,44.77±8.25,30.56±7.71),联合用药组下调最显著;各用药组均出现轻度白细胞抑制(t =3.16,3.08,3.37,P<0.01),联合用药组抑制程度与单一用药组比较差异无统计学意义(P>0.05),肝、肾功能各指标比较差异均无统计学 意义(P>0.05)。结论ATRA联合As2 O3在体内能够协同抑制膀胱癌BIU-87细胞移植瘤的生长和血管生成,仅有白细胞轻度抑制,对肝肾功能无毒副作用。%Objective To investigate the inhibitory effects and related toxicity of all-trans-retinoic acid(ATRA) combined with arsenic trioxide(As2O3) on transplanted human bladder neoplasms in nude mice.Methods The subcutaneously transplanted tumor models of human bladder neoplasms in nude mice were established and then it was randomly divided into four teams: Saline group, ATRA group, As2 O3 group and the combination of ATRA and As2 O3 group.Each group

  4. Tracking the transformation and transport of arsenic sulfide pigments in paints : synchrotron-based X-ray micro-analyses

    NARCIS (Netherlands)

    Keune, Katrien; Mass, Jennifer; Meirer, Florian; Pottasch, Carol; van Loon, Annelies; Hull, Alyssa; Church, Jonathan; Pouyet, Emeline; Cotte, Marine; Mehta, Apurva

    2015-01-01

    Realgar and orpiment, arsenic sulfide pigments used in historic paints, degrade under the influence of light, resulting in transparent, whitish, friable and/or crumbling paints. So far, para-realgar and arsenic trioxide have been identified as the main oxidation products of arsenic sulfide pigments.

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

    Science.gov (United States)

    Au, W Y

    2011-12-01

    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.

  6. AMELIORATION OF GENOTOXICITY BY PAPAYA EXTRACT INDUCED BY ARSENIC CONTAMINATED DRINKING WATER

    Directory of Open Access Journals (Sweden)

    DHARMSHILA KUMARI

    2013-01-01

    Full Text Available Arsenic is an established genotoxic carcinogen in human. Arsenic trioxide (0.04mg/animal when administeredorally daily to albino swiss mice for 15 continuous days, increased the incidence of abnormalities to 30.6% inmeiotic metaphase chromosome, 5.88% in the gross morphology of sperm head and decreased the sperm countper unit volume of caput epididymal suspension to 64.16 in comparison to the control. The concurrent treatmentof papaya fruit extract and arsenic trioxide significantly decreased the abnormalities to19.6% in meioticchromosome, 4.16% in the sperm head morphology and increased the mean count of sperm to 82.28. Theincrease in abnormality of meiotic chromosome as well as abnormality in gross morphology of the sperm headand decrease in sperm count, as observed upon arsenic trioxide treatment, were ameliorated by the aqueouspapaya fruit extract. Therefore, it is suggested that the papaya fruit extract may reduce the risk of arsenic-inducedgenotoxicity.

  7. Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

    Directory of Open Access Journals (Sweden)

    Anshu Jain

    2015-01-01

    Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

  8. Effects of Fas in combined treatment of TRAIL and arsenic trioxide-induced apoptosis in human gastric cancer cells%死亡受体Fas在TRAIL联合三氧化二砷诱导人胃癌细胞凋亡中的作用

    Institute of Scientific and Technical Information of China (English)

    段晓秋; 王晶; 申维喜; 杨宇

    2012-01-01

    OBJECTIVE: To study the effects of Fas in combined treatment of TRAIL(tumor necrosis factor-related apoptosis-inducing ligand) and arsenic trioxide(As2O3)-induced apoptosis in human gastric cancer SGC-7901 cells. METHODS: SGC-7901 cells were cultured in vitro, Sense and Antisense SGC-7901 cells were obtained from transfection of sense and antisense oligo nucleic acid, respectively. Untransfected, Sense and Antisense cells were treated with 0.5 μ g/ml As2O3+0.2 μ g/ml TRAIL, respectively. Cell proliferation was evaluated by MTT assay after 24, 48 and 72 h; cell colony morphologies were examined under inverted microscope after 48 h; apoptosis rate measured by DAPI staining and flow cytometer; and Fas, FADD and Parp expression determined by Western blot. RESULTS: Treatment by Fas antisense oligo nucleic acid transfection decreased the number of dead cells as detected by microscopy, exerted cell growth inhibition and As2O3+TRAIL-induced apoptosis effects. The expressions of Fas, FADD and activated Parp were all down-regulated (P<0.05). CONCLUSION: Fas signaling pathway may be important in the process of SGC-7901 apoptosis induced by combined treatment of As2O3 and TRAIL.%目的:探讨Fas在肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)与三氧化二砷(arsenic trioxide,As2O3)联合诱导人胃癌细胞凋亡过程中的作用.方法:采用体外培养人低分化胃腺癌细胞SGC-7901,分别以Fas正义、反义寡核苷酸转染SGC-7901细胞获得Sense、Antisense细胞.以0.5μg/ml As2O3+0.2μg/ml TRAIL分别处理未转染细胞、Sense组细胞以及Antisense组细胞,采用MTT法检测24、48、72 h后细胞增殖情况;倒置显微镜观察联合作用48 h后细胞集落形态;DAPI染色法、流式细胞仪技术检测48 h时细胞凋亡率;Western blot法检测48 h细胞中Fas、FADD以及Parp表达情况.结果:与未转染组和Sense组细胞比较,转染Fas反义

  9. Treatment of relapsed or refractory multiple myeloma by arsenic trioxide and Thalidomide、ascorbic acid%亚砷酸联合反应停、维生素C治疗难治性复发性多发性骨髓瘤

    Institute of Scientific and Technical Information of China (English)

    郭子文; 许晓军; 周云香; 林淑华

    2014-01-01

    目的:观察亚砷酸(ATO)联合反应停、维生素C (VitC)治疗难治性复发性多发性骨髓瘤(MM)的疗效及安全性。方法:19例难治复发MM患者,应用亚砷酸(10mg/d)联合反应停(200~300mg/d)、VitC(2g/d),连用4周。结果:部分缓解(PR)47%,疾病稳定(SD)32%,疾病进展(PD)21%。主要不良反应为白细胞减少、消化道反应及肝功能损害。结论:ATO联合反应停、VitC治疗难治性复发性MM有效率较高,且毒副反应低,很有临床应用前景。%Objective: To observe the efficacy and side effects of arsenic trioxide(ATO) and Thalidomide、ascorbic acid(VitC)in the treatment of relapsed or refractory multiple myeloma (MM). Methods: patients with relapsed or refractory MM were treated by ATO(10 mg/d)and Thalidomide(200~300 mg/d) 、VitC(2g/d) lasting 4 weeks.Results: The partial remission(PR) rate was 47%. The stable disease(SD) rate was 32% and the progressive disease(PD) rate was 21%. The main side effects were leukocytopenia, digestive tract reaction and liver function damage. Conclusion: The regiment(ATO+ Thalidomide+ VitC) is effective and low adverse reaction for the treatment of relapsed or refractory MM.It has a prospect of clinical application.

  10. Combination of arsenic trioxide and chemotherapy in the treatment of PLZF/RARα positive acute promyelocytic leukemia patient:a case report and literature review%伴PLZF/RARα阳性急性早幼粒细胞白血病的治疗:附1例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    刘凯奇; 刘兵城; 周春林; 秘营昌; 魏述宁; 张广吉; 王建祥

    2012-01-01

    To improve the diagnosis and therapy of acute promyelocytic leukemia(APL)with positive PLZF/RARa fusion gene. Method: We reviewed the patient's clinical features,laboratory results, treatment and following up. Result:This patient was diagnosed APL with PLZF/RARαa( + )by morphologic,immunophenotypic, histochemistry, genetic and molecular studies. Complete hematologic remission was obtained after induction chemotherapy which used arsenic trioxide (ATO) with combined chemotherapy. Until now, the patient was still in CR1. Conclusion:The patient with PLZF/RARαa( + )can achieve CR and prolong the survival time through ATO with combined chemotherapy.%目的:提高对伴PLZF/RARα融合基因阳性的急性早幼粒细胞白血病(APL)诊断和治疗的认识.方法:报道1例伴PLZF/RARα融合基因阳性APL的诊断、治疗经过及随访情况.结果:患者经骨髓形态学、组织化学、免疫分型、染色体、融合基因等检查确诊为APL伴PLZF/RARα融合基因阳性,予以三氧化二砷(ATO)联合化疗达到完全缓解(CR)后,继续予以ATO联合化疗强化巩固治疗.随访11个月,患者仍处于CR1期.结论:伴PLZF/RARα融合基因阳性APL可采用ATO联合化疗诱导、巩固治疗,延长患者生存时间.

  11. Breast Tumor Detection and Treatment Using Tarvacin Labeled with Arsenic Radionuclides

    Science.gov (United States)

    2009-04-01

    for Trisenox (arsenic trioxide) in the treatment of myelodysplastic syndromes . Leukemia, 2003. 17(8): p. 1499-507. 9. Marinsky , J.A., The...Das, and S.K. Saha , Separation of carrier-free arsenic from germanium. Journal of Radioanalytical and Nuclear Chemistry, 1998. 227(1-2): p. 181-182

  12. The revival of the ancient drug-arsenic

    Institute of Scientific and Technical Information of China (English)

    黄晓军

    2003-01-01

    Arsenic, a natural substance, has been used as a traditional Chinese medicine for more than a thousand years. However, this medicine fell into disuse in the 1930s following the advent of radiotherapy and conventional cytotoxic drugs and reports about arsenic poisoning from its long-term low-dose ingestion. Until the late 1970s, it had its rebirth when a series of research papers from China described the successful application of AiLing-1,1 a traditional Chinese compound, containing arsenic trioxide (ATO) and other ingredients. Research into the molecular mechanisms of arsenic action has furthered clinical application of this drug.

  13. Cellular arsenic transport pathways in mammals.

    Science.gov (United States)

    Roggenbeck, Barbara A; Banerjee, Mayukh; Leslie, Elaine M

    2016-11-01

    Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors. Considerable inter-individual variability in susceptibility to arsenic-induced disease and toxicity exists, and the reasons for such differences are incompletely understood. Transport pathways that influence the cellular uptake and export of arsenic contribute to regulating its cellular, tissue, and ultimately body levels. In the current review, membrane proteins (including phosphate transporters, aquaglyceroporin channels, solute carrier proteins, and ATP-binding cassette transporters) shown experimentally to contribute to the passage of inorganic, methylated, and/or glutathionylated arsenic species across cellular membranes are discussed. Furthermore, what is known about arsenic transporters in organs involved in absorption, distribution, and metabolism and how transport pathways contribute to arsenic elimination are described.

  14. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Jaroslav, S.

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3 to 7 km. Settled fly-ash contained 0.0004 to 0.75 percent arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed.

  15. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, J.

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3-7 km. Settled fly-ash contained 0.0004-0.75% arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed. 5 references.

  16. The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy.

    Science.gov (United States)

    Falchi, Lorenzo; Verstovsek, Srdan; Ravandi-Kashani, Farhad; Kantarjian, Hagop M

    2016-04-15

    The therapeutic potential of arsenic derivatives has long been recognized and was recently rediscovered in modern literature. Early studies demonstrated impressive activity of this compound in patients with relapsed acute promyelocytic leukemia (APL). Over the last 2 decades, intravenous arsenic trioxide has been used successfully, both alone and in combination with other agents, for the treatment of APL and, with some success, of other myeloid neoplasms. Arsenic trioxide is currently part the standard of care for patients with APL. More recently, oral formulations of this compound have been developed and are entering clinical practice. In this review, the authors discuss the evolution of arsenic in the treatment of APL and other myeloid neoplasms.

  17. Arsenic in the aetiology of cancer.

    Science.gov (United States)

    Tapio, Soile; Grosche, Bernd

    2006-06-01

    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.

  18. Mechanisms of Arsenic Trioxide on Invasion and Adhesion of Human Breast Cancer Xenograft Tumor in Nude Mice%三氧化二砷影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk 机制

    Institute of Scientific and Technical Information of China (English)

    周艳; 吴振村; 程健君

    2015-01-01

    目的:探讨三氧化二砷(arsenic trioxide, AS2 O3)影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk作用机制。方法成功建立人乳腺癌裸鼠移植瘤模型,随机分为实验组(AS2 O3)和对照组(生理盐水)。7 d后观察肿瘤体积的变化,流式细胞术检测肿瘤组织细胞凋亡情况及两组荷瘤裸鼠肿瘤组织中基质金属蛋白酶-9(MMP-9)和细胞间黏附分子-1(ICAM-1)的表达情况。结果实验组荷瘤裸鼠肿瘤体积明显低于对照组,差异有统计学意义;实验组荷瘤裸鼠肿瘤组织细胞凋亡率明显高于对照组(P <0.01);实验组 ICAM-1表达明显高于对照组(P <0.05);实验组 MMP-9表达低于对照组(P <0.05)。结论AS2 O3对人乳腺癌裸鼠移植瘤具有明显的抑瘤作用,可降低肿瘤组织侵袭性增加其黏附性,其作用机制可能与蛋白酪氨酸激酶 Syk 的表达有关。%Objective To explore the mechanisms of arsenic trioxide (As2 O3 )on invasion and adhe-sion of human breast cancer xenograft tumor in nude mice.Methods Xenografted breast carcinoma in nude mice was established and the mice models were divided randomly into two groups,namely experi-mental (treated with AS2 O3 )and control group (treated with saline).After 7 days,the changes in xen-ograft tumor volume were measured,and the apoptosis of tumor cells were detected by flow cytometry. The expression of matrix metalloproteinase-9 (MMP-9)and intercellular adhesion molecular-1 (ICAM-1) were also detected using flow cytometry.Results The tumor volume of experimental group was signifi-cantly reduced compared with that of control group;while the tumor cell apoptosis of experimental group was higher than that of control group (P < 0.01 );Experimental group showed significantly increased ICAM-1 expression (P <0.05)and reduced MMP-9 expression (P <0.05)compared with control group. Conclusion As2 O3 could inhibit the growth of human breast cancer in

  19. Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-11-01

    Full Text Available The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS. More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1, heat shock 70 kDa protein 9 (HSPA9 and pyruvate kinase M2 (PKM2, were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

  20. Effects of co-treatment with puerariae radix flavones and arsenic trioxide on proliferation and apoptosis of Kasumi-1 cells and HL-60 cells%葛根总黄酮联合三氧化二砷对Kasumi-1和HL-60细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    唐宇宏; 邵化敏; 朱红青; 姜鹏君; 季建敏; 沈群

    2011-01-01

    目的 探讨葛根总黄酮(PRF)联合三氧化二砷(ATO)对M2型急性髓系白血病细胞株Kasumi-1和HL-60细胞增殖和凋亡的影响.方法 以100 μg/mL PRF和1μmoL/L ATO联合处理Kasumi-1和HL-60细胞48 h(RRF+ ATO组),MTT法检测细胞增殖抑制率,Annexin V-FITC/PI双染法流式细胞术检测细胞早期凋亡率,Real-Time PCR检测凋亡抑制基因Bcl-2、Survivin mRNA表达,Western blotting检测细胞凋亡相关蛋白酶Caspase-3、-8、-9的表达.设立单用100μg/mL PRF的PRF处理组和空白对照组.结果 RRF+ ATO组Kasum-1细胞增殖抑制率、早期凋亡率以及Caspase-3、-9表达均显著高于PRF处理组(P<0.05),细胞中Bcl-2 mRNA表达的下调趋势明显.RRF+ ATO组HL-60细胞各项指标检测结果 与PRF处理组比较差异均无统计学意义(P>0.05).结论 PRF联合ATO能有效抑制Kasumi-1细胞增殖并诱导早期凋亡,而对HL-60细胞则无明显影响.%Objective To investigate the effects of co-treatment with puerariae radix flavones (PRF) and arsenic trioxide ( ATO) on proliferation and apoptosis of Kasumi-1 cells and HL-60 cells of acute myeloid leukemia Ml. Methods Kasumi-1 cells and HL-60 cells were treated with 100 jig/mL PRF and 1 funol/L ATO for 48 h (RRF + ATO group). MTT assay was employed to measure the inhibition rate of cell proliferation, Annexin V-FITC/PI double staining was used to determine the early apoptosis rate by flow cytometry, the expression of Bcl-2 and Survivin mRNA was detected by Real-Time PCR, and the expression of Caspase-3, Caspase-8 and Caspase-9 protein was detected by Western blotting. Cells only treated with 100 (ig/mL PRF were served as PRF group, and blank control group was also established. Results The inhibition rate of cell proliferation, early apoptosis rate and expression of Caspase-3 and Caspase-9 protein of Kasumi-1 cells in RRF + ATO group were significantly higher than those in PRF group (P 0.05). Conclusion Co-treatment with PRF and ATO can effectively

  1. Puerarin Synergizes with Arsenic Trioxide for the Apoptosis of Human Glioblastoma Cells through the Protein Kinase/p38 Mitogen-activated Protein Kinases Pathway%葛根素与三氧化二砷协同作用通过Akt/p38途径促进人胶质瘤细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    羊轶驹; 孙振球

    2012-01-01

    目的:研究葛根素(PRN)是否通过Akt/p38途径协同三氧化二砷(As2O3)促进人胶质瘤细胞的凋亡.方法:MTT检测细胞的存活率,流式细胞仪(FCM)技术检测细胞的凋亡状态,蛋白免疫印迹(Immunoblotting)检测细胞phosphorylated Akt和p38-MAPK,Cleaved Caspase-3蛋白的表达,PCR检测Caspase-3的mRNA的表达.结果:PRN协同As2O3降低人胶质瘤细胞U87的存活.与对照组相比,PRN(16μM)组,As2O3(2μM)组显著增加细胞内钙水平(1.13±0.015),(1.18±0.33).此外,PRN能够协同As2O3增加细胞内钙(1.34±0.72),下调蛋白phosphorylated Akt,上调phosphorylated p38-MAPK和Cleaved Caspase-3蛋白及Cleaved Caspase-3 mRNA表达水平.结论:PRN协同As2O3增加胶质瘤细胞内钙水平,抑制细胞存活.此外,PRN联合As2O3下调phosphorylated Akt,增强phosphorylated p38-MAPK和Cleaved Caspase-3的表达,进而促进肿瘤细胞凋亡.PRN可能成为临床上辅助As2O3治疗肿瘤中的潜在的辅助治疗药物.%Objective: To investigate whether puerarin (PRN) synergizes with arsenic trioxide (As2O3) in facilitating the apoptosis of human glioblastoma cell line U87 through the protein kinase (Akt)/p 38 mitogen-activated protein kinases (p38-MAPK) pathway. Methods: The 3-(4,5-deimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide technique was performed to detect cell survival. Flow cytometry was applied to calculate cell apoptosis, and immunoblot technique was used to verify the protein expressions of phosphorylated Akt, p38-MAPK, and cleaved caspase-3. In addition, caspase-3 mRNA levels were detected by real-time polymerase chain reaction. Results: PRN synergized with As2O3 to decrease the survival of human glioblastoma cell line U87. A single dosage each of PRN (16 μM; 1.13±0.015) and As2O3 (2 μM; 1.18±0.33) significantly increased the intracellular calcium concentration. Moreover, PRN synergized with As2O3 to increase the in-tracellular calcium concentration (1.34±0.72) compared with the findings in

  2. Clinical study of children with acute promyelocytic leukemia treated with arsenic trioxide with positive PML -RARa fusion gene%以亚砷酸为主的方案治疗 PML-RARa 阳性急性早幼粒细胞白血病

    Institute of Scientific and Technical Information of China (English)

    朱嘉莳; 蒋慧; 陆正华; 杨静薇; 邵静波; 李红; 廖雪莲; 张娜

    2016-01-01

    未来的发展趋势。%Objective To evaluate the efficacy of different treatment regimens for children with acute promye-locytic leukemia (APL)with positive PML -RARa fusion gene.Methods Thirty -two newly diagnosed APL patients were included in this study,treated either with all -trans -retinoic acid (ATRA)and chemotherapy (CT)(group A) or with ATRA and arsenic trioxide (ATO)(group B).Clinical situation and clinical efficacy were analyzed in patients in different groups.They were also separated into low risk group,intermediate risk group and high risk group according to different risk criteria.Clinical characteristics,complete remission,long -time survival and urine arsenic concentra-tion were analyzed and compared.Results (1 )Fourteen of 1 5 patients (93.3%)in group A achieved hematological complete remission (HCR)with a median time of 38 days (28 -63 days).Sixteen of 1 7 patients (94.1 %)in group B achieved HCR with a median time of 29 days (1 0 -42 days),which was significantly shorter than group A,and there was a significant difference between 2 groups(t =3.53,P =0.002).(2)The 5 -year event -free survival (EFS)of group A and group B was (60.0 ±1 2.6)% and (81 .9 ±9.5)%,respectively;the 5 -year EFS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =1 .1 5,P =0.28).The 5 -year overall survival (OS)of group A and group B was (72.2 ±1 1 .9)% and (94.1 ±5.7)%,respectively,the 5 -year OS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =2.88,P =0.1 6).(3)The 5 -year EFS of low plus intermediate group and high risk group patients was (74.0 ±1 0.1 )% and (64.8 ±1 4.3)%,the 5 -year EFS of low plus intermediate group was almost 1 0% higher than high risk group,but there was no significant difference between the 2 groups(χ2 =0.1 4,P =0.71 ).The 5 -year OS of low plus intermediate group and high risk group patients was (84.7 ±8.1 )% and (71 .3 ±1 4.1 )%,the 5 -year OS of

  3. Advances in Management of Acute Promyelocytic Leukemia with Arsenic Trioxide

    Institute of Scientific and Technical Information of China (English)

    MA Jun

    2007-01-01

    @@ Acute promyelocytic leukemia (APL), with specific features in cell morphology, is classified as M3 by French-American-British (FAB).Among M3, 95% of patients show specific chromosome translocation t(15;17)q(22;21) with PML-RAR α fusion gene, and 5% of patients show other subtypes. According to the statistical analysis of 2 540 adult acute myeloid leukemia (AML)cases in Harbin Institute of Hematology & Oncology, APL accounted for 23%.

  4. Arsenic toxicity in mice and its possible amelioration

    Institute of Scientific and Technical Information of China (English)

    R. J. Verma; Archana Vasu, Abdu; Alim Saiyed

    2004-01-01

    Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose- dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver) and kidney of arsenic- treated mice. Succinic dehydrogenase(SDH) and phosphorylase(only in the liver activities were significantly reduced in a dose-dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic-treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose-dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic-induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic-induced toxicities in the liver and kidney of mice.

  5. Arsenic ototoxicity

    Institute of Scientific and Technical Information of China (English)

    Gulin Gokçen Kesici

    2016-01-01

    High levels of arsenic are found in many parts of the world and more than 100 million people may have been exposed to it. There is growing evidence to indicate that arsenic has a deleterious effect on the auditory system. This paper provides the general information of arsenic and its ototoxic effects.

  6. 尿碘的过硫酸铵消化-低砷量砷铈催化分光光度测定法的化学动力学研究与应用%Chemical kinetics study and application of a method with low usage amount of arsenic trioxide for determining urinary iodine by arsenite-ceric catalytic spectrophotometry using ammonium persulfate digestion

    Institute of Scientific and Technical Information of China (English)

    张亚平; 黄嫣红; 李呐; 张淑琼

    2013-01-01

    Objective To study the chemical kinetics characteristics in a new revised method with low usage amount of arsenic trioxide for determining urinary iodine by arsenite-ceric catalytic spectrophotometry using ammonium persulfate digestion,and to study the impact of operating bias in arsenite-ceric reaction temperature and reaction time on final results in this method.Methods The absorbances (A) of arsenite-ceric reaction of iodine standard series were measured at different reaction temperature and time,and the results were analyzed according to the chemical kinetics equation.The change values and half-life of A values of the new revised method and the current standard method were calculated.The chemical kinetics model of reaction system for this new revised method was deduced from experimental results.The calculation formula of result relative error for urinary iodine determination was deduced based on constants reaction temperature and reaction time and reaction rate constant factor.The result relative errors caused by operation deviation of reaction temperature or reaction time in the determination of urinary iodine were calculated.Results The usage amount of arsenious acid solution in the new revised method was only a quarter of usage amount of the current standard method(WS/T 107-2006).A values of each concentration of standard curve series at different reaction time t were obtained,the lnA to t mapping was a straight line,the linear correlation coefficients were-0.9995--0.9999.These results were in accord with the characteristic of chemical first-order reaction.Relationships between the reaction rate constant K and the reaction temperature T in the temperature range of 20-35 ℃ were well accord with Arrhenius equation.The A values and iodine concentrations (C) at various experimental temperatures showed good C =a + blnA linear relation,the absolute value of the linear correlation coefficient(| r |) > 0.9990.After calculation and comparison of changes in

  7. Gene Analysis of Arsenic Trioxide—induced Apoptosis of Lymphoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGZidong; LIWeiyu; 等

    2002-01-01

    Objective The effect of arsenic trioxide on apoptosis gene expression of Raji cell was explored when Raji cells were incubated with 0.5μmol/L of arsenic trioxide for 6h。Methods Cell culture,extraction and isolation of mRNA,preparation of probes labeled with fluorescence,hybridization technique of DNA chip(each chip containing 200 apoptosis genes,Chinese Shanghai Biostar,In.)were used.Results Arsenic trioxide induced significant changes in 10%(20/200 genes)of the apoptosis genes:18 genes were downregulated,only two upregulated.In particular,inhibitors of apoptosis protein,such as X-linked inhibitor of apoptosis protein,were significantly downregulated.P53 and the other apoptosis genes were also downregulatec.Of the upregulated genes,high expression of heat-shock protein could promote apoptosis of Raji cells.Conclusion The inhibitors of apoptosis protein play an important role in the process of arsenic trioxide-induced apoptosis of Raji cells.

  8. Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

    Energy Technology Data Exchange (ETDEWEB)

    Sun Lu [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Yan Xiulan [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Liao Xiaoyong, E-mail: liaoxy@igsnrr.ac.cn [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Wen Yi; Chong Zhongyi; Liang Tao [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China)

    2011-12-15

    The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level ({>=}10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: > Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. > P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. > Phenanthrene suppresses arsenic translocation from roots to fronds. > Phenanthrene causes As(III) elevation in roots while reduction in fronds. > Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

  9. The impact of gene NDRG1 silence on the inhibitory effect of arsenic trioxide to cervical cancer%沉默NDRG1基因与三氧化二砷对宫颈癌抑制作用的研究

    Institute of Scientific and Technical Information of China (English)

    张海艳; 耿晓星; 马荣; 唐丽萍

    2012-01-01

    Objective To observe the impact of gene NDRG1 silence on the inhibitory effect of arsenic trioxide ( As2Oj) to the growth of cervical cancer HeLa cell, and discuss the mechanism of inhibitory effect of As2O3 on cervical cancer and their correlation with NDRG1 gene. Methods miRNA interference vector of gene NDRGlwas construced and stably transfected into human cervical cancer HeLa cells. The expression of NDRG1 mRNA in cervical cancer HeLa cells was investigated by RT-PCR technique. As203of different concentrations was used to act on HeLa cells before and after transfection. MTT colorimetry method was used to test the growth and apoptosis of these cells. Results Semi-quantitative RT-PCR technique showed that miRNA interference vector of gene NDRG1 was successfully transfected into cervical cancer HeLa cells, and could effectively inhibit the expression of NDRG1 mRNA. As2O3 could inhibit the growth of HeLa cells before and after transfection and the difference was statistically significant in a concentration dependent manner(P<0. 05) ,and the inhibition enhanced with the extension of time. The highest inhibiting rate was (49. 9 ±0. 6)% in HeLa cells and (43. 1 ±0.8)% in transtecled HeLa cells of 12. 0u,mol/L As2O3at 72h. The inhibiting effect of the same concentration As2 0, to HeLa cells after transfection was weaker than HeLa cells before transfection (P < 0.05). Conclusion The silence of gene NDRG1 can decrease the inhibiting effect of As2O3 to the growth of HeLa cells, indicating that the inhibiting effect of As2O3 to the growth of Hela cells is correlated to gene NDRG1.%目的 观察沉默细胞分化相关基因NDRG1在三氧化二砷(As2O3)抑制宫颈癌HeLa细胞生长过程中的作用,探讨As2O3对宫颈癌的抑制作用与NDRG1基因的相关性.方法 构建NDRG1基因的miRNA干扰载体,稳定转染人宫颈癌HeLa细胞,半定量RT-PCR检测转染后HeLa细胞中NDRG1 mRNA的表达;不同浓度As2O3分别作用于转染及未转染HeLa细

  10. 多发性骨髓瘤患者 DLC-1基因甲基化及三氧化二砷诱导 DLC-1基因去甲基化的研究%Hypermethylation of CpG island of DLC-1 gene and arsenic trioxide-induced DLC-1 gene demethylation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    付海英; 沈建箴; 吴淡森

    2014-01-01

    目的:探讨人多发性骨髓瘤(MM)肝癌缺失基因1(DLC-1)启动子区CpG岛甲基化情况,以及三氧化二砷( As2 O3)诱导DLC-1基因的去甲基化作用。方法采用甲基特异性PCR 法( MSP)定性检测2008至2012年来自福建医科大学附属协和医院血液内科的52例MM患者DIC基因甲基化状态,反转录( RT)-PCR检测MM患者和人骨髓瘤U266细胞系DLC-1基因的表达情况;采用重亚硫酸盐测序PCR( BSP)法定量检测As2 O3作用前、后人骨髓瘤细胞株U266其DLC-1基因的甲基化状态;荧光定量 PCR 检测U266细胞用药前、后DLC-1基因、DNA甲基转移酶基因( DNMT1、DNMT3a、DNMT3b) mRNA 的表达变化。结果 MM 患者 DLC-1基因的甲基化比例为71.15%(37/52)。 U266细胞DLC-1基因呈甲基化,DLC-1基因不表达;经0.5、1.0、2.0μmol/L As2 O3作用后72 h U266细胞DLC-1基因甲基化率由95.38%下降至63.07%、30.00%及7.69%;荧光定量PCR检测经0.5、1.0、2.0μmol/L As2 O3作用后72 h U266细胞DLC-1基因mRNA表达与未加药组相比分别为其(1.60±0.09)、(3.66±0.17)、(5.29±0.15)倍,而DNMT1、DNMT3a、DNMT3b基因mRNA表达下调(均P<0.05)。结论 DLC-1基因甲基化在MM患者中较为常见,这可能为MM的诊断和治疗提供借鉴;As2 O3可诱导DLC-1基因去甲基化,使DLC-1基因表达上调,恢复其活性,为MM去甲基化治疗提供新思路。%Objective To explore the role of hypemethylation of DLC-1 gene in the pathogenesis of multiple myeloma ( MM ) and examine the effects of arsenic trioxide ( As2 O3 )-induced demethylation of DLC-1 gene in U266 cell line.Methods The methylation status of DLC-1 gene was detected by methylation specific PCR ( MSP ) in MM patients from 2008 to 2012.And the expression of DLC-1 gene mRNA was determined by reverse transcription-polymerase chain reaction ( RT-PCR ).Methylation statuses of DLC-1 gene exposed to As 2 O3 were

  11. 三氧化二砷对肝癌HepG2细胞形成血管生成拟态的影响及其机制%Influence of arsenic trioxide in vasculogenic mimicry of HepG2 cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    宋海林; 王雪雯; 段晶晶; 周明; 杨莉

    2014-01-01

    目的:探讨三氧化二砷(AS2 O3)对肝癌 HepG2细胞血管生成拟态(VM)形成的影响,初步阐明AS2 O3对 VM抑制的可能作用机制。方法:应用CCK-8法测定 AS2 O3对 HepG2细胞作用72 h的半数抑制浓度(IC50);以 Matrigel胶体外三维培养 HepG2细胞,将其分为空白对照组、1/2 IC50 AS2 O3组和 IC50 AS2 O3组, IPP软件计算 VM的数量、长度和面积,Western blotting法检测 VM相关蛋白 VE-cadherin、基质金属蛋白酶2(MMP-2)、凋亡相关蛋白含半胱氨酸的天冬氨酸蛋白水解酶3(caspase-3)和增殖细胞核抗原(PCNA)的表达。结果:AS2 O3作用 HepG2细胞72 h 后 IC50为10μmol · L-1。与对照组比较,1/2 IC50 AS2 O3组和IC50 AS2 O3组 VM数量、长度和面积明显减少(P<0.01);与1/2 IC50 AS2 O3组比较,IC50 AS2 O3组 VM 数量、长度和面积亦明显减少(P<0.05);与对照组比较,1/2 IC50 AS2O3组和 IC50 AS2O3组 VE-cadherin 和MMP-2蛋白表达水平降低(P<0.05),而 caspase-3和 PCNA 蛋白表达水平无明显变化(P>0.05)。结论:AS2 O3抑制 HepG2细胞形成VM,其作用机制可能与抑制拟态通路相关蛋白VE-cadherin和MMP-2的表达有关。%Objective To investigate the influence of arsenic trioxide (AS2 O3 )in the vasculogenic mimicry (VM ) of HepG2 cells, and to preliminary clarify the possible mechanism of inhibition of AS2 O3 on the VM. Methods Themean inhibitory concentration (IC50 )of AS2 O3 72 h after treatment of HepG2 cells was calculated by CCK-8 assay.The HepG2 cells were cultured on 3-D Matrigel and randomly divided into control group, 1/2 IC50 AS2 O3 group and IC50 AS2 O3 group.IPP software was used to calculate the number,length and area of VM,and the expression levels of VM-related proteins VE-cadherin and MMP-2, apoptotic-related protein caspase-3 and proliferation-related protein PCNA were detected by Western blotting method.Results The IC50 of AS2 O3 was 10

  12. 三氧化二砷洗脱支架抑制猪损伤冠状动脉局部炎性因子的表达%The effects of arsenic trioxide eluting stents on expression of inflammatory factors in injured coronary arteries in pigs

    Institute of Scientific and Technical Information of China (English)

    田文杰; 杨巍; 葛均波; 陆浩; 沈雳; 龚飞荣; 王克强; 邹云增

    2009-01-01

    目的 探讨三氧化二砷(As2O3)多聚左旋乳糖酸(PLLA)涂层支架对猪损伤冠状动脉局部炎性因子表达及炎性细胞浸润的影响,了解As2O3洗脱支架对局部炎性反应的作用. 方法 在8只小型家猪的前降支、回旋支和右冠状动脉随机双盲植入裸金属支架(裸支架组)、西罗莫司洗脱支架和As2O3洗脱支架,7 d处死,检测支架段血管单核细胞趋化蛋白(MCP)-1、白细胞介素(IL)-6蛋白和mRNA表达,HE和免疫组化检测炎性细胞浸润,体外观察As2O3对人T淋巴细胞的凋亡诱导作用. 结果裸支架组MCP-1蛋白和mRNA表达分别为0.857±0.053和0.724±0.027,IL-6蛋白和mRNA表达分别为0.551±0.032和1.015±0.041,As2O3洗脱支架和西罗莫司洗脱支架均降低支架段血管MCP-1(分别为0.421±0.055和0.406±0.042)和IL-6(分别为0.151±0.032和0.146±0.051)蛋白的表达(P<0.01),并同时降低MCP-1(分别为0.338±0.047和0.327±0.051)和IL-6(分别为0.531±0.052和0.523±0.061)mRNA的表达(P<0.01),As2O3洗脱支架和西罗莫司洗脱支架段血管局部炎性细胞浸润较裸支架组明显减少.体外细胞培养显示,As2O3具有诱导入T淋巴细胞凋亡作用. 结论 As2O3洗脱支架具有减少猪损伤冠状动脉炎性细胞浸润和抑制炎性因子MCP-1、IL-6表达的作用,诱导炎性细胞凋亡可能是其抗炎机制之一.%Objective To observe the effects of eluting stents coated with arsenic trioxide(As2O3)and suspended in poly-L-lactic acid(PLLA)on expression of monocyte chemoattractant protein-1 (MCP-1)and interleukin-6(IL-6)and to assess the effects of As2O3 eluting stents on local inflammatory reaction in injured coronary arteries in pigs. Methods Bare metal stents,rapamycin eluting stents and As2O3-eluting stents were randomly and double-blindly implanted into the anterior descending branches,circumflex branches and right coronary arteries in eight pigs.Animals were sacrificed and coronary arteries were isolated 7 days

  13. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.

    Science.gov (United States)

    Zhang, Hai-Nan; Yang, Lina; Ling, Jian-Ya; Czajkowsky, Daniel M; Wang, Jing-Fang; Zhang, Xiao-Wei; Zhou, Yi-Ming; Ge, Feng; Yang, Ming-Kun; Xiong, Qian; Guo, Shu-Juan; Le, Huang-Ying; Wu, Song-Fang; Yan, Wei; Liu, Bingya; Zhu, Heng; Chen, Zhu; Tao, Sheng-Ce

    2015-12-01

    Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies.

  14. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  15. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Schoolmeester, W.L.; White, D.R.

    1980-02-01

    Arsenic poisoning continues to require awareness of its diverse clinical manifestations. Industry is the major source of arsenic exposure. Although epidemiologic studies strongly contend that arsenic is carcinogenic, there are little supportive research data. Arsenic poisoning, both acute and chronic, is often overlooked initially in the evaluation of the patient with multisystem disease, but once it is suspected, many accurate methods are available to quantitate the amount and duration of exposure. Treatment with dimercaprol remains the mainstay of therapy, and early treatment is necessary to prevent irreversible complications.

  16. microRNAs expression profile in acute promyelocytic leukemia cell differentiation induced by all-trans retinoic acid and arsenic trioxide%全反式维甲酸和三氧化二砷诱导急性早幼粒细胞白血病细胞分化前后微小RNA表达变化

    Institute of Scientific and Technical Information of China (English)

    吴勇; 李先芳; 杨景辉; 廖晓莹; 陈元仲

    2012-01-01

    目的 研究急性早幼粒细胞白血病(APL)细胞分化前后微小RNA(miRNA,miR)表达变化.方法 采用全反式维甲酸(ATRA)和三氧化二砷(As2O3)诱导APL细胞系NB4 细胞分化,瑞氏-姬姆萨染色观察细胞形态,流式细胞术检测细胞表面标志CD11b的表达,用实时定量RT-PCR检测miRNA表达谱miR-15b、miR-16、miR-34a、miR-107、miR-124a、miR-146、miR-155、miR-181a、miR-223、miR-342、let7c等miRNA的表达水平,用2-△△Ct法计算miRNA相对表达水平.收集15例APL初诊和15例APL缓解期患者骨髓单个核细胞(MNC),用RT-PCR检测MNC miRNA 的表达水平,用2-△Ct法计算miRNA表达水平.结果 ATRA作用NB4细胞96 h,miR-15b、miR-16、miR-107、miR-223、miR-342表达水平均显著上调,分别为对照组的3.40、4.22、5.41、20.03和5.29倍,As2O3作用NB4细胞96 h,miR-15b、miR-16、miR-107、miR-223、miR-342表达水平也显著上调,分别为对照组的3.62、2.49、2.58、4.27和1.94倍,除miR-15b外,ATRA处理组miR-16、miR-107、miR-223和miR-342表达水平上调程度均高于As2O3处理组,其中尤以miR-223为甚.ATRA和As2O3治疗后缓解期APL患者miR-15b、miR-16、miR-107、miR-181a、miR-223和miR-342表达水平(2-△Ct值)分别为0.4137、0.6367、0.1260、0.0522、0.6611和0.0280,而APL初诊患者miR-15b、miR-16、miR-107、miR-181a、miR-223、miR-342表达水平分别为0.0751、0.2022、0.0425、0.3064、0.1733和0.0090,APL缓解期miR-15b、miR-16、miR-107、miR-223和miR-342表达水平高于APL初诊者(P值均<0.05),而APL缓解期miR-181a表达水平低于APL初诊者(P<0.05).结论 特定miRNA参与APL细胞分化过程.%Objective To study the expression profile of microRNAs in acute promyelocytic leukemia (APL) cells during differentiation. Methods Differentiation of APL cell line NB4 cells was induced by all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3). Morphological and immunological assay was performed by Wright-Giemsa staining and flow

  17. Adverse effect of arsenic trioxide treatment on vital organs in the process of treating childhood acute promyelocytic leukemia%三氧化二砷致小儿急性早幼粒细胞白血病器官功能损害的临床研究

    Institute of Scientific and Technical Information of China (English)

    王弘; 王晔; 李爽; 迟昨非; 郝良纯

    2014-01-01

    Objective To explore the adverse effect of arsenic trioxide (As2O3) on liver,kidney and heart function during treating children patients with acute promyelocytic leukemia (APL) at therapeutic dose.Methods Sixty-five APL cases received As2O3 by intravenous drip and organic toxicity were selected as our subjects.The indices of liver,heart and kidney were measured.Results Of all subjects,19 cases(29.2%) occurred liver damage,including 15 cases(23.1%) mild and 4 cases(6.2%) moderate toxicity.The levels of alanine aminotransferase of patients before treatment was (19.9 ±9.5) U/L,and (24.3 ± 11.8) U/L,(25.0 ± 14.4) U/L at 1 st and 2nd weeks after treatment,higher than those before the treatment (P < 0.05).However,level of alanine aminotransferase was back to normal at 3th weeks after treatment.Meanwhile the levels of aspartate aminotransferase at 1st,2nd and 3th weeks after treatment were (38.3 ± 16.5),(39.1 ± 15.5),(35.3 ± 20.6) U/L respectively,higher than that before treatment((28.5 ± 8.8) U/L,P < 0.05 or 0.01),and it was back to normal at 4th weeks.(2) The levels of urinary cystatin C were (2.51 ± 1.45) mg/L,(3.05 ± 1.13) mg/L,(2.46 ± 1.21) mg/L at 2nd,3th,4th weeks after treatment,significantly higher than that before treatment ((1.98 ±0.68) mg/L,P <0.05 or 0.01).And the levels of urinary β2 microglobulin at 2nd,3th,4th weeks after treatment were significantly higher than that before treatment (P <0.05 or 0.01) and back to normal at 5 weeks after treatment.(3) Nine cases at remission stage showed the symptoms of palpitation,precordial discomfort and increased heart rate,and all those symptoms were mild.And the symptoms disappear at the 3th week after the treatment.Creatine kinase at the 2nd weeks after treatment was (90.2 ± 32.5) U/L,higher than that before treatment ((78.5 ± 22.3) U/L).The levels of creatine kinase isoenzyme at 2nd,3th weeks after treatment were (8.3 ± 4.8) U/L,(8.5 ± 5.6) U/L,higher than that before treatment ((6.3

  18. Defect and electrical properties of nanocrystalline tungsten trioxide

    Institute of Scientific and Technical Information of China (English)

    Yang Xin-Sheng; Wang Yu; Dong Liang; Qi Li-Zhen; Zhang Feng

    2004-01-01

    Nanocrystalline tungsten trioxide particles were prepared by a wet-chemical method. Transmission electron microscope (TEM) analysis shows that the average grain size is about 15nm. The oxygen deficiency of nanometre-sized sample is higher than that of ordinary tungsten trioxide. The electric conductivity increases because of high oxygen deficiency. Ironic relaxation polarization and crystallographic shear (CS) planes theory were used to explain the unusual dielectric characteristic of nanocrystalline tungsten trioxide.

  19. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Low, D.G.

    1971-01-01

    The use of arsenic in ant poisons, herbicides, and insecticides affords the necessary contact with the poison by pets. Treatment was discussed in relation to two circumstances: very early poisoning in which the owner has observed ingestion of the arsenic, and when the signs of the poisoning are evident. Treatment for early ingestion involves emptying the stomach before the arsenic can pass in quantity into the intestine. This is followed with a 1% solution of sodium bicarbonate, with the administering of 3 to 6 mg of apomorphine. When signs of arsenic toxicity are already advanced, there is little advantage to be gained by either gastric lavage or administration of an emetic. The treatment then consists of the intramuscular administration of dimercaprol (BAL) at a dosage of 3 mg/lb of body weight three times a day until recovery. This is the specific antidote for arsenic. 1 reference.

  20. Sandwich heterostructures of antimony trioxide and bismuth trioxide films: Structural, morphological and optical analysis

    Science.gov (United States)

    Condurache-Bota, Simona; Praisler, Mirela; Gavrila, Raluca; Tigau, Nicolae

    2017-01-01

    Thin film heterostructures can be advantageous since they either exhibit novel or a combination of the properties of their components. Here we propose sandwich-type of heterostructures made of antimony trioxide and bismuth trioxide thin films, which were deposited on glass substrates by thermal vacuum deposition at three substrate temperatures, 50° Celsius apart. Their morphology and optical properties are studied as compared to the corresponding monolayers. It was found that even small substrate temperature changes strongly influence their morphology, increasing their roughness, while the optical transmittance shows a slight decrease as compared with the individual layers. The corresponding absorption coefficient exhibits intermediate values as compared to the component oxides, while the energy bandgaps for the indirect allowed transitions move towards the Infrared when overlapping the antimony and bismuth trioxides.

  1. Effects of arsenic poisoning on neuronal cell apoptosis and mRNA and protein expression of calpain 1,calpain 2,and cdk5/p25

    Institute of Scientific and Technical Information of China (English)

    李新

    2014-01-01

    Objective To study the effect of arsenic on neuronal cell apoptosis and the mRNA and protein expression of calpain 1,calpain 2,and cyclin-dependent kinases 5(cdk5)/p25 and to provide a scientific basis for the research on neurotoxic mechanism of arsenic trioxide(As2O3).Methods Primary cultured rat neurons were divided into untreated control group,dimethyl sulfoxide

  2. Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

    Science.gov (United States)

    Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

    2017-01-01

    Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As2O3). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues.

  3. Arsenic exposure disrupts the normal function of the FA/BRCA repair pathway.

    Science.gov (United States)

    Peremartí, Jana; Ramos, Facundo; Marcos, Ricard; Hernández, Alba

    2014-11-01

    Chronic arsenic exposure is known to enhance the genotoxicity/carcinogenicity of other DNA-damaging agents by inhibiting DNA repair activities. Interference with nucleotide excision repair and base excision repair are well documented, but interactions with other DNA repair pathways are poorly explored so far. The Fanconi anemia FA/BRCA pathway is a DNA repair mechanism required for maintaining genomic stability and preventing cancer. Here, interactions between arsenic compounds and the FA/BRCA pathway were explored by using isogenic FANCD2(-/-) (FA/BRCA-deficient) and FANCD2(+/+) (FA/BRCA-corrected) human fibroblasts. To study whether arsenic disrupts the normal FA/BRCA function, FANCD2(+/+) cells were preexposed to subtoxic concentrations of the trivalent arsenic compounds methylarsonous acid (MMA(III)) and arsenic trioxide (ATO) for 2 weeks. The cellular response to mitomicin-C, hydroxyurea, or diepoxybutane, typical inducers of the studied pathway, was then evaluated and compared to that of FANCD2(-/-) cells. Our results show that preexposure to the trivalent arsenicals MMA(III) and ATO induces in corrected cells, a cellular FA/BRCA-deficient phenotype characterized by hypersensitivity, enhanced accumulation in the G2/M compartment and increased genomic instability--measured as micronuclei. Overall, our data demonstrate that environmentally relevant arsenic exposures disrupt the normal function of the FA/BRCA activity, supporting a novel source of arsenic co- and carcinogenic effects. This is the first study linking arsenic exposure with the FA/BRCA DNA repair pathway.

  4. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Low, D.G.

    1974-01-01

    The use of arsenic in ant poisons, herbicides, and insecticides affords the necessary contact with the poison by pets. The gastrointestinal tract appears to suffer the greatest though there may also be injury to the liver and kidneys. The treatments discussed were in relation to very early poisoning in which the owner had observed ingestion of the arsenic, and when the signs of the poisoning were evident. Early observation treatment included emptying the stomach before the arsenic passed in quantity into the intestine. If the signs of toxicity were already advanced, then the treatment consisted of the intramuscular administration of dimercaprol (BAL) at a dosage of 3 mg/lb of body weight three times a day until recovery. l reference.

  5. Arsenic poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Furr, A.

    1977-01-01

    The route of arsenic exposure is usually by ingestion, thus the veterinarian is concerned with treating either an acute or a peracute condition. The arsenic compounds are considered to be highly toxic with a rapid onset of clinical signs. The toxicity and rapidity of onset are variable, depending upon the age and the species of animal. The chemical form and solubility of the toxicant also play a role in the course of the clinical syndrome. Inorganic arsenicals inhibit the sulfhydryl enzyme systems which are essential for normal cellular respiration and for metabolism of fats and carbohydrates. Therapeutic measures are intended to either remove or inactivate the unabsorbed material in the intestine, protect the alimentary tract, reverse the toxic syndrome and restore the homeostatic equilibrium of the animal. 5 references.

  6. Arsenic in Food

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Foodborne Illness & Contaminants Metals Arsenic Share ... of the Method used to Measure Arsenic in Foods Inductively Coupled Plasma-Mass Spectrometric Determination of Arsenic, ...

  7. An Aerosol Condensation Model for Sulfur Trioxide

    Energy Technology Data Exchange (ETDEWEB)

    Grant, K E

    2008-02-07

    This document describes a model for condensation of sulfuric acid aerosol given an initial concentration and/or source of gaseous sulfur trioxide (e.g. fuming from oleum). The model includes the thermochemical effects on aerosol condensation and air parcel buoyancy. Condensation is assumed to occur heterogeneously onto a preexisting background aerosol distribution. The model development is both a revisiting of research initially presented at the Fall 2001 American Geophysical Union Meeting [1] and a further extension to provide new capabilities for current atmospheric dispersion modeling efforts [2]. Sulfuric acid is one of the most widely used of all industrial chemicals. In 1992, world consumption of sulfuric acid was 145 million metric tons, with 42.4 Mt (mega-tons) consumed in the United States [10]. In 2001, of 37.5 Mt consumed in the U.S., 74% went into producing phosphate fertilizers [11]. Another significant use is in mining industries. Lawuyi and Fingas [7] estimate that, in 1996, 68% of use was for fertilizers and 5.8% was for mining. They note that H{sub 2}SO{sub 4} use has been and should continue to be very stable. In the United States, the elimination of MTBE (methyl tertiary-butyl ether) and the use of ethanol for gasoline production are further increasing the demand for petroleum alkylate. Alkylate producers have a choice of either a hydrofluoric acid or sulfuric acid process. Both processes are widely used today. Concerns, however, over the safety or potential regulation of hydrofluoric acid are likely to result in most of the growth being for the sulfuric acid process, further increasing demand [11]. The implication of sulfuric acid being a pervasive industrial chemical is that transport is also pervasive. Often, this is in the form of oleum tankers, having around 30% free sulfur trioxide. Although sulfuric acid itself is not a volatile substance, fuming sulfuric acid (referred to as oleum) is [7], the volatile product being sulfur trioxide

  8. Mineral trioxide aggregate apexification: A novel approach

    Science.gov (United States)

    Purra, Aamir Rashid; Ahangar, Fayaz Ahmed; Chadgal, Sachin; Farooq, Riyaz

    2016-01-01

    The treatment of choice for necrotic teeth with immature root is apexification, which is induction of apical closure to produce more favorable conditions for conventional root canal filling. The most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate (MTA). MTA offers the option of a two-visit apexification procedure so that the fragile tooth can be restored immediately. However, difficulty in placing the material in the wide apical area requires the use of an apical matrix. Materials such as collagen, calcium sulfate, and hydroxyapatite have been used for this purpose. This article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials. PMID:27563191

  9. THE SETTING MECHANISM OF MINERAL TRIOXIDE AGGREGATE

    Directory of Open Access Journals (Sweden)

    Halenur Altan

    2016-01-01

    Full Text Available Mineral trioxide aggregate (MTA is a powder containing calcium silicate composed of hydrophilic particles which harden at the presence of moisture. MTA was initially introduced as a root end filling material. Due its practical advantages that include superior biocompatility, effective sealing capability, and the ability to improve regeneration of the pulp and peripheral root tissues, it is used in different clinical applications such as pulp capping, apexification, pulpotomy and perforation. Despite being a promising material in endodontic treatment, MTA is not commonly used. Long setting time is the main clinical disadvantage of MTA. The aim of this review is to provide an overview of the current literature concerning the setting mechanism of MTA, accelerators and devices used to evaluate various steps of the hardening process.

  10. The chemical composition of mineral trioxide aggregate

    Directory of Open Access Journals (Sweden)

    Camilleri Josette

    2008-01-01

    Full Text Available Mineral trioxide aggregate (MTA is composed of Portland cement, with 4:1 addition of bismuth oxide added so that the material can be detected on a radiograph. The cement is made up of calcium, silicon and aluminium. The main constituent phases are tricalcium and dicalcium silicate and tricalcium aluminate. There are two commercial forms of MTA, namely the grey and the white. The difference between the grey and the white materials is the presence of iron in the grey material, which makes up the phase tetracalcium alumino-ferrite. This phase is absent in white MTA. Hydration of MTA occurs in two stages. The initial reaction between tricalcium aluminate and water in the presence of calcium sulphate results in the production of ettringite. Tricalcium and dicalcium silicate react with water to produce calcium silicate hydrate and calcium hydroxide, which is leached out of the cement with time.

  11. Determination of arsenic in antimony ingot and antimony trioxide by hydride generation-atomic fluorescence spectrometry%氢化物发生-原子荧光光谱法测定锑锭及三氧化二锑中的砷

    Institute of Scientific and Technical Information of China (English)

    钱光敏; 赵国杏

    2012-01-01

    The antimony slab and antimonous oxide samples were dissolved by sulfuric acid and hydrochloric acid, respectively. The Sb3+ in solution was precipitated with sodium hydroxide to separate trace arsenic from matrix antimony. The thiourea-ascorbic acid was added to reduce As5+ to As3+. Then, the arsenic in antimony slab and antimonous oxide was determined by atomic fluorescence spec-trometry. The hydride generation conditions were investigated: the concentration of reducing agent potassium borohydride was 25 g/L, the determination medium was 20% (V/V) hydrochloric acid, and the dosage of thiourea - ascorbic acid solution was 5 mL. The interference test of coexisting elements showed that, the interference of residual antimony in solution after precipitation could be fully eliminated by adding 1 mL of tartaric acid solution. Other impurity elements in sample did not interfere with the determination of arsenic after adding thiourea-ascorbic acid solution. The detection limit of method was 0. 156 ng/mL. The antimony slab and antimonous oxide samples were analyzed by the proposed method, and the relative standard deviation (RSD) was 0. 95%-1.2%. The determination results were consistent with those obtained by national standard methods.%采用硫酸溶解锑锭样品,盐酸溶解三氧化二锑样品,用氢氧化钠溶液使Sb3+沉淀从而使基体锑与微量砷分离,通过加入硫脲-抗坏血酸将As5+还原成As3+,然后在原子荧光仪上测定锑锭及三氧化二锑中的砷.对氢化物发生条件进行考察,确定还原剂硼氢化钾的浓度为25 g/L、测定介质为20%(V/V)盐酸、硫脲-抗坏血酸溶液用量为5 mL.共存元素干扰试验表明,沉淀后溶液中残留少量锑的干扰在加入1 mL酒石酸溶液后可以完全消除,而样品中其他杂质元素在加入硫脲-抗坏血酸溶液后不干扰砷的测定.方法的检出限为0.156 ng/mL.对锑锭及三氧化二锑样品进行分析,相对标准偏差为0.95%~1.2%,测定

  12. Down-regulation of wt1 expression in leukemia cell lines as part of apoptotic effect in arsenic treatment using two compounds.

    Science.gov (United States)

    Glienke, Wolfgang; Chow, Kai U; Bauer, Nina; Bergmann, Lothar

    2006-08-01

    Arsenic trioxide (As2O3) induces remission in patients with acute promyelocytic leukemia (APL). To better understand molecular mechanisms of arsenic actions, this study investigated the effect of two different arsenic compounds on gene expression of apoptosis and cellular proliferation related genes. The Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As2O3) and sodium arsenite (NaAsO2) at concentrations between 0 - 10 microM for up to 48 h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1 mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1 microM arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell lines HL-60 and K562. There were no major differences encountered between compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the up-regulation of par-4 may contribute to the induction of apoptosis rather than down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene.

  13. Earth Abides Arsenic Biotransformations

    Science.gov (United States)

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P.

    2015-01-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice. PMID:26778863

  14. Earth Abides Arsenic Biotransformations

    Science.gov (United States)

    Zhu, Yong-Guan; Yoshinaga, Masafumi; Zhao, Fang-Jie; Rosen, Barry P.

    2014-05-01

    Arsenic is the most prevalent environmental toxic element and causes health problems throughout the world. The toxicity, mobility, and fate of arsenic in the environment are largely determined by its speciation, and arsenic speciation changes are driven, at least to some extent, by biological processes. In this article, biotransformation of arsenic is reviewed from the perspective of the formation of Earth and the evolution of life, and the connection between arsenic geochemistry and biology is described. The article provides a comprehensive overview of molecular mechanisms of arsenic redox and methylation cycles as well as other arsenic biotransformations. It also discusses the implications of arsenic biotransformation in environmental remediation and food safety, with particular emphasis on groundwater arsenic contamination and arsenic accumulation in rice.

  15. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  16. Arsenic drinking water regulations in developing countries with extensive exposure.

    Science.gov (United States)

    Smith, Allan H; Smith, Meera M Hira

    2004-05-20

    The United States Public Health Service set an interim standard of 50 microg/l in 1942, but as early as 1962 the US Public Health Service had identified 10 microg/l as a goal which later became the World Health Organization Guideline for drinking water in 1992. Epidemiological studies have shown that about one in 10 people drinking water containing 500 microg/l of arsenic over many years may die from internal cancers attributable to arsenic, with lung cancer being the surprising main contributor. A prudent public health response is to reduce the permissible drinking water arsenic concentrations. However, the appropriate regulatory response in those developing countries with large populations with much higher concentrations of arsenic in drinking water, often exceeding 100 microg/l, is more complex. Malnutrition may increase risks from arsenic. There is mounting evidence that smoking and arsenic act synergistically in causing lung cancer, and smoking raises issues of public health priorities in developing countries that face massive mortality from this product. Also, setting stringent drinking water standards will impede short term solutions such as shallow dugwells. Developing countries with large populations exposed to arsenic in water might reasonably be advised to keep their arsenic drinking water standards at 50 microg/l.

  17. Acute arsenic self-poisoning for suicidal purpose in a dentist: a case report.

    Science.gov (United States)

    Yilmaz, Y; Armagan, E; Olmez, Of; Esen, M; Alkis, N; Dolar, E

    2009-01-01

    Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

  18. Pulp-Capping with Mineral Trioxide Aggregate

    Directory of Open Access Journals (Sweden)

    Peycheva Kalina

    2015-11-01

    Full Text Available There are two considerations for direct pulp capping - accidental mechanical pulp exposure and exposure caused by caries. Mineral trioxide aggregate (MTA was used as pulp-capping material to preserve the vitality of the pulpal tissues. Follow-up examinations revealed that treatment was successful in preserving pulpal vitality and continued development of the tooth. On the basis of available information, it appears that MTA is the material of choice for some clinical applications. Material and methods: Cases 18 - 8 teeth with grey MTA, 10 teeth with white MTA; diagnose: Pulpitis chronica ulcerosa, Electro pulpal test (EOD - 30-35 μA, pre-clinical X-ray - without changes in the structures, follow ups for 4 years. Successful treatments: without clinical symptoms and changes in the X-rays: 5 teeth with grey MTA, 8 teeth with white MTA for period of 4 years. Unsuccessful treatments: Clinical symptoms and sometimes changes in the X-ray: 3 with grey MTA, 2 with white MTA. MTA is an appropriate material for pulp-capping and follow-up examinations revealed that the treatment was successful in preserving pulpal vitality.

  19. Cryptic exposure to arsenic.

    Science.gov (United States)

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  20. Cryptic exposure to arsenic

    Directory of Open Access Journals (Sweden)

    Rossy Kathleen

    2005-01-01

    Full Text Available Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  1. Poisoning by coal smoke containing arsenic and fluoride

    Energy Technology Data Exchange (ETDEWEB)

    An, D.; He, Y.G.; Hu, Q.X. [Guizhou Sanitary and Epidemiological Station, Guiyang (China)

    1997-02-01

    An investigation was made into a disease involving skin pigmentation, keratosis of the hands and feet, dental discoloration, and generalized bone and joint pain, stiffness and rigidity, in the village of Bazhi, Zhijin County, Ghizhou Province, People`s Republic of China. Measurements were made of the arsenic and fluoride levels of coal, water, air, food, urine and hair in Bazhi and a control village, Xinzhai, in which coal with a low arsenic content was used. Up to 188 people, including children, in Bazhi and 752 in Xinzhai, were examined for the presence of chronic arsenium, skeletal fluorosis, dental fluorosis and electrocardiogram abnormalities. The coal in Bazhi was found to contain high levels of arsenic and fluoride resulting, after burning in homes without an adequate chimney systems, in pollution of air and food with arsenic and fluoride. The coal in Xinzhai did not cause arsenic pollution but did produce a higher level of fluoride pollution. It was concluded that the endemic disease in Bazhi was caused by pollution by coal smoke containing arsenic and fluoride. It is suggested that arsenic may act synergistically with fluoride so that a lower level of fluoride may produce fluoride toxicity with dental and skeletal fluorosis.

  2. Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy

    Science.gov (United States)

    Gibaud, Stéphane; Jaouen, Gérard

    Although arsenic is a poison and has a predominantly unfavorable reputation, it has been used as pharmaceutical agent since the first century BC. In 1786, Thomas Fowler reported the effects of arsenic in the cure of agues, remittent fevers, and periodic headaches. From this time on and despite abusive use, some interesting indications began to appear for trypanosomiasis, syphilis, and blood diseases. The first significant organoarsenical drug (atoxyl) was synthesized by Pierre Antoine Béchamp in 1859 by chemically reacting arsenic acid with aniline but additional experimentations on the properties of arsenic led Paul Ehrlich, the founder of chemotherapy, to the discovery of salvarsan in 1910. From the Second World War, Ernst A.H. Friedheim greatly improved the treatment of trypanosomiasis by melaminophenyl arsenicals. Until the 1990s some organoarsenicals were used for intestinal parasite infections but carcinogenic effects were displayed and all the drugs have been withdrawn in USA, in Europe, and elsewhere. In 2003, arsenic trioxide (Trisenox®) was re-introduced for the treatment of very specific hematological malignancies.

  3. Arsenic pollution sources.

    Science.gov (United States)

    Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

    2008-01-01

    Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

  4. Arsenic removal from water

    Science.gov (United States)

    Moore, Robert C.; Anderson, D. Richard

    2007-07-24

    Methods for removing arsenic from water by addition of inexpensive and commonly available magnesium oxide, magnesium hydroxide, calcium oxide, or calcium hydroxide to the water. The hydroxide has a strong chemical affinity for arsenic and rapidly adsorbs arsenic, even in the presence of carbonate in the water. Simple and commercially available mechanical methods for removal of magnesium hydroxide particles with adsorbed arsenic from drinking water can be used, including filtration, dissolved air flotation, vortex separation, or centrifugal separation. A method for continuous removal of arsenic from water is provided. Also provided is a method for concentrating arsenic in a water sample to facilitate quantification of arsenic, by means of magnesium or calcium hydroxide adsorption.

  5. Arsenic poisoning in livestock.

    Science.gov (United States)

    el Bahri, L; Ben Romdane, S

    1991-06-01

    Arsenic is an important heavy metal intoxicant to livestock. Arsenical pesticides present significant hazards to animal health. The toxicity of arsenic varies with several factors--its chemical form, oxidation states, solubility. The phenylarsonic compounds are the least toxic and are used as feed additives in swine and poultry rations. However, roxarsone has a higher absolute toxicity than arsanilic acid. The mechanism of action is related to its reaction with sulfhydryl groups values to enzyme function and to its ability to uncouple oxydative phosphorylation. Most animals excrete arsenic quite readily. Toxicoses caused by inorganic and aliphatic organic arsenicals result in a different clinical syndrome than that from the phenylarsonic compounds. Arsenic poisoning may be confused with other types of intoxication. The specific antidote for inorganic arsenical poisoning is dimercaprol (BAL).

  6. Summary of four scientific studies on Arsenicum album high dilution effect against Arsenic intoxication in mice

    Directory of Open Access Journals (Sweden)

    Laurence Terzan

    2012-09-01

    arsenic intoxication. Results: Compared to controls, Arsenicum album 30cH induced a significant decrease in accumulation of arsenic in 4 tissues namely liver, spleen, kidney and testis in intoxicated mice. In addition, both Arsenicum album 6cH, 30cH and 200cH reduced chromosome aberrations, sperm head abnormality frequencies and activities of acid and alkaline phosphatases, aspartate and alanine aminotransferases and lipid peroxidation, while mitotic index and activities of glutathione, catalase and succinate dehydrogenase were increased compared to controls. Conclusion: Altogether, theses results provide evidence of protective potentials of the Arsenicum album dilution against acute and chronic arsenic intoxication in mice. They also offer a new hypothesis that the mechanism of the homeopathic dilution could act through regulation of expression of certain genes. This explanation seems to be plausible because all biomarker tests are regulated by specific genetic regulatory mechanisms [6]. keywords: Arsenicum album, arsenic intoxication, enzymatic and biomarker toxicity. References: [1] WHO. WHO Guidelines for Drinking Water Quality, Vol. 2, 2nd edition. Geneva: WHO, 1996, 940–9. [2] Cazin JC, Cazin M, Gaborit JL, Chaoui A, Boiron J, Belon P, et al. A study of the effect of decimal and centesimal dilutions of arsenic on the retention and mobilization of arsenic in the rat. Hum Toxicol 1987;6:315–20. [3] Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30 in reducing toxic effects produced by of arsenic trioxide in mice. I. On rate accumulation of arsenic in certain vital organs. Comp Ther Med 1998;6:178–84. [4] Pathikrit Banerjee. Evidences of Protective Potentials of Microdoses of Ultra-high Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide. eCAM 2009; 1-10. [5] Pathikrit Banerjee, Comparative Efficacy of Two Microdoses of a

  7. Programming voltage reduction in phase change memory cells with tungsten trioxide bottom heating layer/electrode.

    Science.gov (United States)

    Rao, Feng; Song, Zhitang; Gong, Yuefeng; Wu, Liangcai; Feng, Songlin; Chen, Bomy

    2008-11-05

    A phase change memory cell with tungsten trioxide bottom heating layer/electrode is investigated. The crystalline tungsten trioxide heating layer promotes the temperature rise in the Ge(2)Sb(2)Te(5) layer which causes the reduction in the reset voltage compared to a conventional phase change memory cell. Theoretical thermal simulation and calculation for the reset process are applied to understand the thermal effect of the tungsten trioxide heating layer/electrode. The improvement in thermal efficiency of the PCM cell mainly originates from the low thermal conductivity of the crystalline tungsten trioxide material.

  8. Arsenic content in Portland cement: A literature review

    Directory of Open Access Journals (Sweden)

    Tenorio de Franca Talita

    2010-01-01

    Full Text Available Portland cement (PC is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

  9. Pulpotomy in deciduous tooth with mineral trioxid aggregate

    OpenAIRE

    Piva,Fabiane; Coelho de Souza, Fábio Herrmann; Meira, Raquel; ROTTA,Gabriela Taube; Volkweiss, Taytianne

    2015-01-01

    Several medicines have been tested and used in the conservative pulp therapy of deciduous teeth, however, the formocresol has being the elected material in the pulpotomies, even not assisting the biocompatibility demands and promoting the fixation of the vital pulp tissue and not its repair. After Mineral Trioxide Aggregate (MTA) appearance as a material with physico-chemical properties that promotes the tissue repair, allied to other important properties, such as the antimicrobial action and...

  10. Construction of a modular arsenic resistance operon in E. coli and the production of arsenic nanoparticles

    Directory of Open Access Journals (Sweden)

    Matthew Charles Edmundson

    2015-10-01

    Full Text Available Arsenic is a widespread contaminant of both land and water around the world. Current methods of decontamination such as phytoremediation and chemical adsorbents can be resource and time intensive, and may not be suitable for some areas such as remote communities where cost and transportation are major issues. Bacterial decontamination, with strict controls preventing environmental release, may offer a cost-effective alternative or provide a financial incentive when used in combination with other remediation techniques. In this study we have produced E. coli strains containing arsenic resistance genes from a number of sources, overexpressing them and testing their effects on arsenic resistance. While the lab E. coli strain JM109 (the wild-type is resistant up to 20 mM sodium arsenate the strain containing our plasmid pEC20 is resistant up to 80 mM. When combined with our construct pArsRBCC arsenic-containing nanoparticles were observed at the cell surface; the elements of pEC20 and pArsRBCC were therefore combined in a modular construct, pArs, in order to evaluate the roles and synergistic effects of the components of the original plasmids in arsenic resistance and nanoparticle formation. We also investigated the use of introducing the lac operator in order to more tightly control expression from pArs. We demonstrate that our strains are able to reduce toxic forms of arsenic into stable, insoluble metallic As(0, providing one way to remove arsenate contamination, and which may also be of benefit for other heavy metals.

  11. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    OpenAIRE

    Harris, Robin B.; Burgess, Jefferey L; Maria Mercedes Meza-Montenegro; Luis Enrique Gutiérrez-Millán; Mary Kay O’Rourke; Jason Roberge

    2012-01-01

    The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and...

  12. Mechanism of apoptosis of human osteosarcoma M-G63 induced by arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    XIAO Tao; LI Kang-hua; FANG Jian-zhen; WANG Wan-chun; LI Gui-yuan

    2005-01-01

    Objective To observe the apoptosis of osteosarcoma MG-63 cells induced by As2O3 and to explore its possible mechanisms. Methods The flowcytometric analysis and transmission electronmicroscope were performed to investigate the inducing apoptosis and inhibitative of As2O3 on osteosarcoma MG-63 cells. In order to study mechanism of apoptosis in MG-63 cells treated with As2 O3, microarray was performed. The down-regulated gene was confirmed by RT-PCR, Northern-blotting. Results After treated with As2O3, hypodiploid peak before G0/G1 phase was observed in MG-63 cells through FCM analysis. Loss of microvilli, condensation and fragmentation of nuclear chromatin, condensation of cytoplasmic organelles, dilatation of the endoplasmic reticulum shrinkage of cells and alterations in cell membranes and apoptosis bodies which were observed in MG-63 cells treated with As2O3 by transmission electronmicroscope. The results of microarray show that As2 O3 induced MG-63 cell apoptosis involves down-regulation of IEX-1 and the down-regulated gene is confirmed by RT-PCR and Northern-blotting.Conclusion The results show that As2 O3 selectively inhibits growth of the solid tumor MG-63 cells by triggering apoptosis and indicates MG-63 induced by As2O3 cell apoptosis may through the IEX-1 pathway.

  13. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  14. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    Science.gov (United States)

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  15. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-08

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  16. Clinical Effects of Arsenic Trioxide by Slowing-intravenous Infusion on Acute Promyelocyte Leukemia

    Institute of Scientific and Technical Information of China (English)

    Jin Zhou; Ran Meng; Bao-feng Yang

    2005-01-01

    @@ Although As2O3 is effective in the treatment of acute promyelocytic leukemia (APL), some side effects, such as leukocytosis which can increase the incidence of cerebral hemorrhage and early death rate, often occur during the early stage of As2O3 treatment. In this paper, the advantages of continuously slow intravenous As2O3 infusion on relieving leukocytosis and decreasing the incidence of cerebral hemorrhage and early death rate were observed clinically.

  17. Transcriptome Profiling of Wheat Seedlings following Treatment with Ultrahigh Diluted Arsenic Trioxide

    Directory of Open Access Journals (Sweden)

    Ilaria Marotti

    2014-01-01

    Full Text Available Plant systems are useful research tools to address basic questions in homeopathy as they make it possible to overcome some of the drawbacks encountered in clinical trials (placebo effect, ethical issues, duration of the experiment, and high costs. The objective of the present study was to test the hypothesis whether 7-day-old wheat seedlings, grown from seeds either poisoned with a sublethal dose of As2O3 or unpoisoned, showed different significant gene expression profiles after the application of ultrahigh diluted As2O3 (beyond Avogadro’s limit compared to water (control. The results provided evidence for a strong gene modulating effect of ultrahigh diluted As2O3 in seedlings grown from poisoned seeds: a massive reduction of gene expression levels to values comparable to those of the control group was observed for several functional classes of genes. A plausible hypothesis is that ultrahigh diluted As2O3 treatment induced a reequilibration of those genes that were upregulated during the oxidative stress by bringing the expression levels closer to the basal levels normally occurring in the control plants.

  18. Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

    Science.gov (United States)

    Moore, D F; O'Callaghan, C A; Berlyne, G; Ogg, C S; Davies, H A; House, I M; Henry, J A

    1994-01-01

    Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL). PMID:8089687

  19. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Watson, Walter H. [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Zhong, Hai [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2011-12-15

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

  20. Arsenic poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    Reagor, J.C.

    Reports of heavy metal intoxication submitted to the Texas Veterinary Medical Diagnostic Laboratory indicate that arsenic is the most common heavy metal intoxicant in Texas. The most frequent sources of arsenic are compounds used as herbicides and cotton defoliants. The misuse of these compounds and subsequent intoxication of cattle is discussed in this paper. 8 references, 1 table.

  1. Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29.

    Science.gov (United States)

    Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C; Han, Sung Gu

    2017-03-15

    Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40μM, 12h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5-10mM, 1h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

  2. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    Directory of Open Access Journals (Sweden)

    Robin B. Harris

    2012-03-01

    Full Text Available The Binational Arsenic Exposure Survey (BAsES was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001, urinary inorganic arsenic concentration (p < 0.001, and urinary sum of species (p < 0.001. Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  3. Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

    Science.gov (United States)

    Roberge, Jason; O'Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L; Harris, Robin B

    2012-04-01

    The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  4. Quantifying synergistic mutual information

    CERN Document Server

    Griffith, Virgil

    2012-01-01

    Quantifying cooperation among random variables in predicting a single target random variable is an important problem in many biological systems with 10s to 1000s of co-dependent variables. We review the prior literature of information theoretical measures of synergy and introduce a novel synergy measure, entitled *synergistic mutual information* and compare it against the three existing measures of cooperation. We apply all four measures against a suite of binary circuits to demonstrate our measure alone quantifies the intuitive concept of synergy across all examples.

  5. ENZYMOLOGY OF ARSENIC METHYLATION

    Science.gov (United States)

    Enzymology of Arsenic MethylationDavid J. Thomas, Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park...

  6. Toxic Substances Portal- Arsenic

    Science.gov (United States)

    ... a naturally occurring element widely distributed in the earth's crust. In the environment, arsenic is combined with ... workplace air (10 µg/m 3 ) for 8 hour shifts and 40 hour work weeks. top References ...

  7. EXAFS study on arsenic species and transformation in arsenic hyperaccumulator

    Institute of Scientific and Technical Information of China (English)

    HUANG Zechun; CHEN Tongbin; LEI Mei; HU Tiandou; HUANG Qifei

    2004-01-01

    Synchrotron radiation extended X-ray absorption fine structure (SR EXAFS) was employed to study the transformation of coordination environment and the redox speciation of arsenic in a newly discovered arsenic hyperaccumulator, Cretan brake (Pteris cretica L. var nervosa Thunb). It showed that the arsenic in the plant mainly coordinated with oxygen, except that some arsenic coordinated with S as As-GSH in root. The complexation of arsenic with GSH might not be the predominant detoxification mechanism in Cretan brake. Although some arsenic in root presented as As(V) in Na2HAsO4 treatments, most of arsenic in plant presented as As(III)-O in both treatments, indicating that As(V) tended to be reduced to As(III) after it was taken up into the root, and arsenic was kept as As(III) when it was transported to the above-ground tissues. The reduction of As(V) primarily proceeded in the root.

  8. Association between chronic arsenic exposure and nutritional status among the women of child bearing age: a case-control study in Bangladesh.

    Science.gov (United States)

    Milton, Abul H; Shahidullah, S M; Smith, Wayne; Hossain, Kazi S; Hasan, Ziaul; Ahmed, Kazi T

    2010-07-01

    The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI 50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

  9. Removal of cobalt from zinc sulphate solution using rude antimony trioxide as additive

    Institute of Scientific and Technical Information of China (English)

    戴军; 王德全; 姜澜; 金曼

    2002-01-01

    The process of cobalt removal from zinc sulphate solution using rude antimony trioxide as an additive was investigated. The rude antimony trioxide was produced in treatment of copper and lead anode mud and its main components are antimony trioxide, antimony arsenate and lead antimonate. Using the rude antimony trioxide as the additive of cobalt removal can not only decrease operation cost of purification but also find out a new way for utilization of the rude antimony trioxide. The effects of temperature, dosage of zinc dust, the rude antimony trioxide, copper ion and solution pH on removal of cobalt were studied. And experimental data using the rude Sb2O3 as additive were compared with those using Sb2O3. The results indicate that using rude Sb2O3 as additive, cobalt concentration in solution could be decreased from 24mg/L to below 1mg/L under about the same conditions as using Sb2O3.

  10. Mineral trioxide aggregate (MTA)-like materials: an update review.

    Science.gov (United States)

    Mohammadi, Zahed; Shalavi, Sousan; Soltani, Mohammad Karim

    2014-09-01

    Mineral trioxide aggregate (MTA) is a multi-application material used in endodontics. It is a mixture of a refined Portland cement and bismuth oxide and trace amounts of SiO₂, CaO, MgO, K₂SO₄, and Na₂SO₄. MTA powder is mixed with supplied sterile water in a 3:1 powder/liquid. Hydrated MTA has an initial pH of 10.2, which rises to 12.5 three hours after mixing. There are several materials derived from MTA such as Endo-CPM Sealer, Ortho MTA, MTA-Fillapex, DiaRoot BioAggregate, MTA Bio, light-cured MTA, tricalcium silicate, and iRoot SP. The purpose of this article is to review MTA-like materials.

  11. Arsenic and dichlorvos: Possible interaction between two environmental contaminants.

    Science.gov (United States)

    Flora, Swaran J S

    2016-05-01

    Metals are ubiquitously present in the environment and pesticides are widely used throughout the world. Environmental and occupational exposure to metal along with pesticide is an area of great concern to both the public and regulatory authorities. Our major concern is that combination of these toxicant present in environment may elicit toxicity either due to additive or synergistic interactions or 'joint toxic actions' among these toxicants. It poses a rising threat to human health. Water contamination particularly ground water contamination with arsenic is a serious problem in today's scenario since arsenic is associated with several kinds of health problems, such arsenic associated health anomalies are commonly called as 'Arsenism'. Uncontrolled use and spillage of pesticides into the environment has resulted in alarming situation. Moreover serious concerns are being addressed due to their persistence in the environmental matrices such as air, soil and surface water runoff resulting in continuous exposure of these harmful chemicals to human beings and animals. Bio-availability of these environmental toxicants has been enhanced much due to anthropological activities. Dreadfully very few studies are available on combined exposures to these toxicants on the animal or human system. Studies on the acute and chronic exposure to arsenic and DDVP are well reported and well defined. Arsenic is a common global ground water contaminant while dichlorvos is one of the most commonly and widely employed organophosphate based insecticide used in agriculture, horticulture etc. There is thus a real situation where a human may get exposed to these toxicants while working in a field. This review highlights the individual and combined exposure to arsenic and dichlorvos on health.

  12. THE SYNERGISTIC EFFECT OF HYBRID FLAME RETARDANTS ON PYROLYSIS BEHAVIOUR OF HYBRID COMPOSITE MATERIALS

    Directory of Open Access Journals (Sweden)

    M. T. ALBDIRY

    2012-06-01

    Full Text Available The aim of this investigation is to comprehensively understand the polymeric composite behavior under direct fire sources. The synergistic effects of hybrid flame retardant material on inhabiting the pyrolysis of hybrid reinforced fibers, woven roving (0°- 45° carbon and kevlar (50/50 wt/wt, and an araldite resin composites were studied. The composites were synthesised and coated primarily by zinc borate (2ZnO.3B2O3.3.5H2O and modified by antimony trioxide (Sb2O3 with different amounts (10-30 wt% of flame retardant materials. In the experiments, the composite samples were exposed to a direct flame source generated by oxyacetylene flame (~3000ºC at variable exposure distances of 10-20 mm. The synergic flame retardants role of antimony trioxide and zinc borate on the composite surface noticeably improves the flame resistance of the composite which is attributed to forming a protective mass and heat barrier on the composite surface and increasing the melt viscosity.

  13. Arsenic, Anaerobes, and Astrobiology

    Science.gov (United States)

    Stolz, J. F.; Oremland, R. S.; Switzer Blum, J.; Hoeft, S. E.; Baesman, S. M.; Bennett, S.; Miller, L. G.; Kulp, T. R.; Saltikov, C.

    2013-12-01

    Arsenic is an element best known for its highly poisonous nature, so it is not something one would associate with being a well-spring for life. Yet discoveries made over the past two decades have delineated that not only are some microbes resistant to arsenic, but that this element's primary redox states can be exploited to conserve energy and support prokaryotic growth ('arsenotrophy') in the absence of oxygen. Hence, arsenite [As(III)] can serve as an electron donor for chemo- or photo-autotrophy while arsenate [As(V)] will serve as an electron acceptor for chemo-heterotrophs and chemo-autotrophs. The phylogenetic diversity of these microbes is broad, encompassing many individual species from diverse taxonomic groups in the Domain Bacteria, with fewer representatives in the Domain Archaea. Speculation with regard to the evolutionary origins of the key functional genes in anaerobic arsenic transformations (arrA and arxA) and aerobic oxidation (aioB) has led to a disputation as to which gene and function is the most ancient and whether arsenic metabolism extended back into the Archaean. Regardless of its origin, robust arsenic metabolism has been documented in extreme environments that are rich in their arsenic content, such as hot springs and especially hypersaline soda lakes associated with volcanic regions. Searles Lake, CA is an extreme, salt-saturated end member where vigorous arsenic metabolism occurs, but there is no detectable sulfate-reduction or methanogenesis. The latter processes are too weak bio-energetically to survive as compared with arsenotrophy, and are also highly sensitive to the abundance of borate ions present in these locales. These observations have implications with respect to the search for microbial life elsewhere in the Solar System where volcanic-like processes have been operative. Hence, because of the likelihood of encountering dense brines in the regolith of Mars (formed by evapo-concentration) or beneath the ice layers of Europa

  14. [Arsenic - Poison or medicine?].

    Science.gov (United States)

    Kulik-Kupka, Karolina; Koszowska, Aneta; Brończyk-Puzoń, Anna; Nowak, Justyna; Gwizdek, Katarzyna; Zubelewicz-Szkodzińska, Barbara

    2016-01-01

    Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine.

  15. Arsenic-mediated nephrotoxicity.

    Science.gov (United States)

    Robles-Osorio, Ma Ludivina; Sabath-Silva, Elizabeth; Sabath, Ernesto

    2015-05-01

    Chronic kidney disease (CKD) is an important global health problem that affects 8-15% of the population according to epidemiological studies done in different countries. Essential to prevention is the knowledge of the environmental factors associated with this disease, and heavy metals such as lead and cadmium are clearly associated with kidney injury and CKD progression. Arsenic is one of the most abundant contaminants in water and soil, and many epidemiological studies have found an association between arsenic and type 2 diabetes mellitus, hypertension and cancer; however, there is a scarcity of epidemiological studies about its association with kidney disease, and the evidence linking urinary arsenic excretion with CKD, higher urinary excretion of low molecular proteins, albuminuria or other markers of renal in injury is still limited, and more studies are necessary to characterize the role of arsenic on renal injury and CKD progression. Global efforts to reduce arsenic exposure remain important and research is also needed to determine whether specific therapies are beneficial in susceptible populations.

  16. Chronic arsenic poisoning.

    Science.gov (United States)

    Hall, Alan H

    2002-03-10

    Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee's lines may be seen. Bone marrow depression is common. 'Blackfoot disease' has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud's phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS).

  17. Arsenic hyperaccumulator Pteris Vittata L. and its arsenic accumulation

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An arsenic hyperaccumulator Pteris vittata L. (Chinese brake) was first discovered in China by means of field survey and greenhouse cultivation. Field survey showed that Chinese brake had large accumulating capacity to arsenic; the orders of arsenic content in different parts of the fern were as follows: leaves>leafstalks>roots, which is totally different from that of ordinary plants; bioaccumulation coefficients of the above ground parts of the fern decreased as a power function of soil arsenic contents. In the control of pot trials with normal unpolluted soil containing 9 mg/kg of arsenic, the bioaccumulation coefficients of the above ground parts and rhizoids of Chinese brake were as high as 71 and 80 respectively. Greenhouse cultivation in the contaminated soil from mining areas has shown that more than 1 times greater arsenic can be accumulated in the leaves of the fern than that of field samples with the largest content of 5070 mg/kg As on a dry matter basis. During greenhouse cultivation, arsenic content in the leaves of the fern increased linearly with time prolonging. Not only has Chinese brake extraordinary tolerance and accumulation to arsenic, but it grew rapidly with great biomass, wide distribution and easy adaptation to different environmental conditions as well. Therefore, it has great potential in future remediation of arsenic contamination. It also demonstrates important value for studies of arsenic physiology and biochemistry such as arsenic absorption, translocation and detoxification mechanisms in plants.

  18. Construction of a Modular Arsenic-Resistance Operon in E. coli and the Production of Arsenic Nanoparticles.

    Science.gov (United States)

    Edmundson, Matthew Charles; Horsfall, Louise

    2015-01-01

    Arsenic is a widespread contaminant of both land and water around the world. Current methods of decontamination such as phytoremediation and chemical adsorbents can be resource and time intensive, and may not be suitable for some areas such as remote communities where cost and transportation are major issues. Bacterial decontamination, with strict controls preventing environmental release, may offer a cost-effective alternative or provide a financial incentive when used in combination with other remediation techniques. In this study, we have produced Escherichia coli strains containing arsenic-resistance genes from a number of sources, overexpressing them and testing their effects on arsenic resistance. While the lab E. coli strain JM109 (the "wild-type") is resistant up to 20 mM sodium arsenate, the strain containing our plasmid pEC20 is resistant up to 80 mM. When combined with our construct pArsRBCC arsenic--containing nanoparticles were observed at the cell surface; the elements of pEC20 and pArsRBCC were therefore combined in a modular construct, pArs, in order to evaluate the roles and synergistic effects of the components of the original plasmids in arsenic resistance and nanoparticle formation. We have also investigated introducing the lac operator in order to more tightly control expression from pArs. We demonstrate that our strains are able to reduce toxic forms of arsenic into stable, insoluble metallic As(0), providing one way to remove arsenate contamination, and which may also be of benefit for other heavy metals.

  19. Arsenic poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    McLennan, M.W.; Dodson, M.E.

    1972-06-01

    A case of acute arsenic poisoning in cattle was reported. The losses occurred on a property in the south east of South Australia. The weather had been hot for two or three days before the death occurred. The tank supplying the water trough had almost run dry. The cattle then attempted to meet their water requirements by drinking from the sheep dipping vat. A sample of rumen contents and a sample of water from the dipping vat were checked for arsenic. The rumen sample contained 45 ppM As/sub 2/O/sub 3/ and the sample of dipping fluid contained 200 ppM As. The lesions observed were similar to earlier reported arsenic poisoning. 5 references.

  20. Environmental source of arsenic exposure.

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  1. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    Science.gov (United States)

    Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

  2. Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yamanoshita, Osamu; Shimizu, Shingo; Ohnuma, Shoko; Furuta, Akio; Yajima, Ichiro; Nizam, Saika; Khalequzzaman, Md; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2013-03-01

    Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

  3. ARSENIC REMOVAL TREATMENT OPTIONS FOR SINGLE FAMILY HOMES

    Science.gov (United States)

    The presentation provides information on POU and POE arsenic removal drinking water treatment systems. The presentation provides information on the arsenic rule, arsenic chemistry and arsenic treatment. The arsenic treatment options proposed for POU and POE treatment consist prim...

  4. Sources and circulation of water and arsenic in the Giant Mine, Yellowknife, NWT, Canada.

    Science.gov (United States)

    Clark, Ian D; Raven, Kenneth G

    2004-06-01

    Recovery of gold from arsenopyrite-hosted ore in the Giant Mine camp, Yellowknife, NWT, Canada, has left a legacy of arsenic contamination that poses challenges for mine closure planning. Seepage from underground chambers storing some 237,000 tonnes of arsenic trioxide dust, has As concentrations exceeding 4000 ppm. Other potential sources and sinks of As also exist. Sources and movement of water and arsenic are traced using the isotopes of water and sulphate. Mine waters (16 ppm As; AsV/AsIII approximately 150) are a mixture of two principal water sources--locally recharged, low As groundwaters (0.5 ppm As) and Great Slave Lake (GSL; 0.004 ppm As) water, formerly used in ore processing and discharged to the northwest tailings impoundment (NWTP). Mass balance with delta18O shows that recirculation of NWTP water to the underground through faults and unsealed drillholes contributes about 60% of the mine water. Sulphate serves to trace direct infiltration to the As2O3 chambers. Sulphate in local, low As groundwaters (0.3-0.6 ppm As; delta34SSO4 approximately 4% and delta18OSO4 approximately -10%) originates from low-temperature aqueous oxidation of sulphide-rich waste rock. The high As waters gain a component of 18O-enriched sulphate derived from roaster gases (delta18OSO4) = + 3.5%), consistent with their arsenic source from the As2O3 chambers. High arsenic in NWTP water (approximately 8 ppm As; delta18OSO4 = -2%) derived from mine water, is attenuated to close to 1 ppm during infiltration back to the underground, probably by oxidation and sorption by ferrihydrite.

  5. The Role of Oxidative Stress in Gastrointestinal Tract Tissues Induced by Arsenic Toxicity in Cocks.

    Science.gov (United States)

    Guo, Ying; Zhao, Panpan; Guo, Guangyang; Hu, Zhibo; Tian, Li; Zhang, Kexin; Zhang, Wen; Xing, Mingwei

    2015-12-01

    Arsenic (As) is a widely distributed trace element which is known to be associated with numerous adverse effects on human beings and animals. Arsenic trioxide (As2O3) is an inorganic arsenical-containing toxic compound. The effect of excessive amounts of As2O3 exposure on gastrointestinal tract tissue damage in cocks is still unknown. This study was conducted to investigate the effect of As2O3 exposure on gastrointestinal tract tissue damage in cocks. In total, 72 1-day-old male Hyline cocks were randomly divided into four groups and fed either a commercial diet or an As2O3 supplement diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days and gastrointestinal tract tissue samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum) were collected at 30, 60, and 90 days. Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA) contents; and hydroxyl radical (OH·)-mediated inhibition were examined. Furthermore, the results demonstrated that MDA content in the gastrointestinal tract was increased, while the activities of CAT, GSH, and GSH-Px and the ability to resist OH· was decreased in the As2O3 treatment groups. Extensive damage was observed in the gastrointestinal tract. These findings indicated that As2O3 exposure caused oxidative damage in the gastrointestinal tract of cocks due to alterations in antioxidant enzyme activities and elevation of free radicals.

  6. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  7. Microbial Transformation of Arsenic

    Science.gov (United States)

    Stolz, J. F.

    2004-12-01

    Whether the source is natural or anthropogenic, it has become evident that arsenic is readily transformed by a great diversity of microbial species and has a robust biogeochemical cycle. Arsenic cycling primarily involves the oxidation of As(III) and the reduction of As(V). Over thirty arsenite oxidizing prokaryotes have been reported and include alpha, beta, and gamma Proteobacteria , Deinocci and Crenarchaeota. At least twenty species of arsenate-respiring prokaryotes are now known and include Crenarchaeota, thermophilic bacteria, low and high G+C gram positive bacteria, and gamma, delta, and epsilon Proteobacteria. These organisms are metabolically diverse, and depending on the species, capable of using other terminal electron acceptors (e.g., nitrate, selenate, fumarate, sulfate). In addition to inorganic forms (e.g., sodium arsenate) organoarsenicals can be utilized as a substrate. The feed additive roxarsone (3-nitro-4-hydroxyphenyl arsonic acid) has been shown to readily degrade leading to the release of inorganic arsenic (e.g., As(V)). Degradation proceeds via the cleavage of the arsenate functional group or the reduction of the nitro functional group and deamination. The rapid degradation (within 3 days) of roxarsone by Clostridium sp. strain OhILAs appears to follow the latter pathway and may involve Stickland reactions. The activities of these organisms affect the speciation and mobilization of arsenic, ultimately impacting water quality.

  8. Arsenic in shrimp from Kuwait

    Energy Technology Data Exchange (ETDEWEB)

    Bou-Olayan, A.H. [Kuwait Univ. (Kuwait); Al-Yakoob, S.; Al-Hossaini, M. [Kuwait Institute for Scientific Research (Kuwait)

    1995-04-01

    Arsenic is ubiquitous in the environment and can accumulate in food via contaminated soil, water or air. It enters the food chain through dry and wet atmospheric deposition. Combustion of oil and coal, use of arsenical fertilizers and pesticides and smelting of ores contributes significantly to the natural background of arsenic in soils and sediments. The metal can be transferred from soil to man through plants. In spite of variation in acute, subacute, and chronic toxic effects to plants and animals, evidence of nutritional essentiality of arsenic for rats, goats, and guinea pigs has been suggested, but has not been confirmed for humans. Adverse toxic effects of arsenic as well as its widespread distribution in the environment raises concern about levels of arsenic in man`s diet. Higher levels of arsenic in the diet can result in a higher accumulation rate. Arsenic levels in marine organisms are influenced by species differences, size of organism, and human activities. Bottom dwellers such as shrimp, crab, and lobster accumulate more arsenic than fish due to their frequent contact with bottom sediments. Shrimp constitute approximately 30% of mean total seafood consumption in Kuwait. This study was designed to determine the accumulation of arsenic in the commercially important jinga shrimp (Metapenaeus affinis) and grooved tiger prawn (Penaeus semisulcatus). 13 refs., 3 figs., 1 tab.

  9. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    Science.gov (United States)

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.

  10. Multidrug resistance protein 1 (ABCC1) confers resistance to arsenic compounds in human myeloid leukemic HL-60 cells.

    Science.gov (United States)

    Xu, Shi; Zhang, Yan Fang; Carew, Micheal W; Hao, Wen Hui; Loo, Jacky Fong Chuen; Naranmandura, Hua; Le, X Chris

    2013-06-01

    Arsenic trioxide (As(2)O(3)) is established as one of the most effective drugs for treatment of patients with acute promyelocytic leukemia, as well as other types of malignant tumors. However, HL-60 cells are resistant to As(2)O(3), and little is known about the underlying resistance mechanism for As(2)O(3) and its biomethylation products, namely, monomethylarsonous acid (MMA(III)) on the treatment of tumors. In the present study, we investigated the molecular mechanisms underlying iAs(III) and its intermediate metabolite MMA(III)-induced anticancer effects in the HL-60 cells. Here, we show that the HL-60 cells exhibit resistance to inorganic iAs(III) (IC(50) = 10 μM), but are relatively sensitive to its intermediate MMA(III) (IC(50) = 3.5 μM). Moreover, we found that the multidrug resistance protein 1 (MRP1), but not MRP2, is expressed in HL-60 cells, which reduced the intracellular arsenic accumulation, and conferred resistance to inorganic iAs(III) and MMA(III). Pretreatment of HL-60 with MK571, an inhibitor of MRP1, significantly increased iAs(III) and MMA(III)-induced cytotoxicity and arsenic accumulations, suggesting that the expression of MRP1/4 may lead to HL-60 cells resistance to trivalent arsenic compounds.

  11. Rural methods to mitigate arsenic contaminated water

    OpenAIRE

    Parajuli, Krishna

    2013-01-01

    Consumption of arsenic contaminated water is one of the burning issues in the rural world. Poor public awareness program about health effects of drinking arsenic contaminated water and the rural methods to mitigate this problem poses a great threat of arsenic poisoning many people of the rural world. In this thesis, arsenic removal efficiency and the working mechanism of four rural and economical arsenic mitigation technologies i.e. solar oxidation and reduction of arsenic (SORAS), Bucket tr...

  12. Mineral trioxide aggregate induces osteoblastogenesis via Atf6

    Directory of Open Access Journals (Sweden)

    Toyonobu Maeda

    2015-06-01

    Full Text Available Mineral trioxide aggregate (MTA has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III and matrix metalloproteinases (MMP-9 and MMP-13, suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin but not Bmp2 (bone morphogenetic protein-2 mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER stress response transcription factor mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6 markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

  13. Photocatalysis and photoelectrochemical properties of tungsten trioxide nanostructured films.

    Science.gov (United States)

    Lai, Chin Wei

    2014-01-01

    Tungsten trioxide (WO₃) possesses a small band gap energy of 2.4-2.8 eV and is responsive to both ultraviolet and visible light irradiation including strong absorption of the solar spectrum and stable physicochemical properties. Thus, controlled growth of one-dimensional (1D) WO₃ nanotubular structures with desired length, diameter, and wall thickness has gained significant interest. In the present study, 1D WO₃ nanotubes were successfully synthesized via electrochemical anodization of tungsten (W) foil in an electrolyte composed of 1 M of sodium sulphate (Na₂SO₄) and ammonium fluoride (NH₄F). The influence of NH₄F content on the formation mechanism of anodic WO₃ nanotubular structure was investigated in detail. An optimization of fluoride ions played a critical role in controlling the chemical dissolution reaction in the interface of W/WO₃. Based on the results obtained, a minimum of 0.7 wt% of NH₄F content was required for completing transformation from W foil to WO₃ nanotubular structure with an average diameter of 85 nm and length of 250 nm within 15 min of anodization time. In this case, high aspect ratio of WO₃ nanotubular structure is preferred because larger active surface area will be provided for better photocatalytic and photoelectrochemical (PEC) reactions.

  14. [Mineral trioxide aggregate (MTA) a success story in apical surgery].

    Science.gov (United States)

    von Arx, Thomas

    2016-01-01

    The objective of apical surgery is to retain teeth with persistent apical pathosis following orthograde root canal treatment if endodontic non-surgical revision is difficult or associated with risks, or is even declined by the patient. Since the most frequent cause of recurrent apical disease is bacterial reinfection from the (remaining) root canal system, the bacteria-tight root-end filling is the most important step in apical surgery. In the early 1990s, mineral trioxide aggregate (MTA) was developed at the Loma Linda University in California/USA. Preclinical studies clearly showed that MTA has a high sealing capability, a good material stability and an excellent biocompatbility. Multiple experimental studies in animals highlighted the mild tissue reactions observed adjacent to this material. Furthermore, histological analysis of the periapical regions demonstrated a frequent deposition of new cementum not only onto the resection plane (cut dentinal surface), but also directly onto MTA. For these reasons, MTA is considered a bioactive material. In 1997 MTA was cleared for clinical use in patients. Multiple prospective clinical and randomized studies have documented high and constant success rates of MTA-treated teeth in apical surgery. A recently published longitudinal study showed that MTA-treated teeth remained stable over five years; hence the high healed rates documented after one year are maintained during long-term observation.

  15. Exceptions in patterns of arsenic compounds in urine of acute promyelocytic leukaemia patients treated with As2O3.

    Science.gov (United States)

    Šlejkovec, Zdenka; Podgornik, Helena; Černelč, Peter; Falnoga, Ingrid

    2016-02-01

    Arsenic trioxide (As(III) in solution) has been shown to be the most active single agent in combating acute promyelocytic leukemia (APL). It is metabolized and excreted via urine as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V), along with excess As(III). In our study eight APL patients were treated (intravenously) with 0.15 mg As2O3/kg/day. During the therapy As(III) and its metabolites were followed in pre- and post-infusion urine using HPLC for separation followed by on-line detection using hydride generation-atomic fluorescence spectrometry. Five patients had a normal excretion pattern of residual arsenic compounds in morning pre-infusion urine, with 15-25% of As(III), 35-55% of DMA, 25-30% of MMA and 1-5% of As(V), while three patients showed unexpected exceptions from typical excretion patterns of arsenic compounds (i) a high DMA/MMA ratio (factor 5.3), (ii) severe As(III) oxidation (10.2% As(III) converted to As(V)) or (iii) the presence of an excessive amount of As(III) (average 30.4% of total arsenic). Intriguing was the occurrence of post-infusion oxidation of As(III) to As(V) observed in almost all patients and being especially high (>40%) in patient with increased residual As(V). Results indicate that arsenic metabolites patterns can be unpredictable. Observed high levels of un-metabolised As(III) are a warning signal for side effects and for routine determination of arsenic metabolites during first days of treatment. High or low percentages of MMA or DMA did not show any observable effect on treatment results, while clear presence of post-infusion As(V) supports theoretical claims of in vivo oxidation (detoxification) of As(III) to As(V) associated with various metabolic processes.

  16. Arsenic poisoning of Bangladesh groundwater

    Science.gov (United States)

    Nickson, Ross; McArthur, John; Burgess, William; Ahmed, Kazi Matin; Ravenscroft, Peter; Rahmanñ, Mizanur

    1998-09-01

    In Bangladesh and West Bengal, alluvial Ganges aquifers used for public water supply are polluted with naturally occurring arsenic, which adversely affects the health of millions of people. Here we show that the arsenic derives from the reductive dissolution of arsenic-rich iron oxyhydroxides, which in turn are derived from weathering of base-metal sulphides. This finding means it should now be possible, by sedimentological study of the Ganges alluvial sediments, to guide the placement of new water wells so they will be free of arsenic.

  17. Homicidal arsenic poisoning.

    Science.gov (United States)

    Duncan, Andrew; Taylor, Andrew; Leese, Elizabeth; Allen, Sam; Morton, Jackie; McAdam, Julie

    2015-07-01

    The case of a 50-year-old man who died mysteriously after being admitted to hospital is reported. He had raised the possibility of being poisoned prior to his death. A Coroner's post-mortem did not reveal the cause of death but this was subsequently established by post-mortem trace element analysis of liver, urine, blood and hair all of which revealed very high arsenic concentrations.

  18. Thiolated arsenicals in arsenic metabolism: Occurrence, formation, and biological implications.

    Science.gov (United States)

    Sun, Yuzhen; Liu, Guangliang; Cai, Yong

    2016-11-01

    Arsenic (As) is a notoriously toxic pollutant of health concern worldwide with potential risk of cancer induction, but meanwhile it is used as medicines for the treatment of different conditions including hematological cancers. Arsenic can undergo extensive metabolism in biological systems, and both toxicological and therapeutic effects of arsenic compounds are closely related to their metabolism. Recent studies have identified methylated thioarsenicals as a new class of arsenic metabolites in biological systems after exposure of inorganic and organic arsenicals, including arsenite, dimethylarsinic acid (DMA(V)), dimethylarsinous glutathione (DMA(III)GS), and arsenosugars. The increasing detection of thiolated arsenicals, including monomethylmonothioarsonic acid (MMMTA(V)), dimethylmonothioarsinic acid (DMMTA(V)) and its glutathione conjugate (DMMTA(V)GS), and dimethyldithioarsinic acid (DMDTA(V)) suggests that thioarsenicals may be important metabolites and play important roles in arsenic toxicity and therapeutic effects. Here we summarized the reported occurrence of thioarsenicals in biological systems, the possible formation pathways of thioarsenicals, and their toxicity, and discussed the biological implications of thioarsenicals on arsenic metabolism, toxicity, and therapeutic effects.

  19. A Phytoremediation Strategy for Arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Richard B.

    2005-06-01

    A Phytoremediation Strategy for Arsenic Progress Report May, 2005 Richard B. Meagher Principal Investigator Arsenic pollution affects the health of several hundred millions of people world wide, and an estimated 10 million Americans have unsafe levels of arsenic in their drinking water. However, few environmentally sound remedies for cleaning up arsenic contaminated soil and water have been proposed. Phytoremediation, the use of plants to extract and sequester environmental pollutants, is one new technology that offers an ecologically sound solution to a devastating problem. We propose that it is less disruptive to the environment to harvest and dispose of several thousand pounds per acre of contaminated aboveground plant material, than to excavate and dispose of 1 to 5 million pounds of contaminated soil per acre (assumes contamination runs 3 ft deep). Our objective is to develop a genetics-based phytoremediation strategy for arsenic removal that can be used in any plant species. This strategy requires the enhanced expression of several transgenes from diverse sources. Our working hypothesis is that organ-specific expression of several genes controlling the transport, electrochemical state, and binding of arsenic will result in the efficient extraction and hyperaccumulation of arsenic into aboveground plant tissues. This hypothesis is supported by theoretical arguments and strong preliminary data. We proposed six Specific Aims focused on testing and developing this arsenic phytoremediation strategy. During the first 18 months of the grant we made significant progress on five Specific Aims and began work on the sixth as summarized below. Specific Aim 1: Enhance plant arsenic resistance and greatly expand sinks for arsenite by expressing elevated levels of thiol-rich, arsenic-binding peptides. Hyperaccumulation of arsenic depends upon making plants that are both highly tolerant to arsenic and that have the capacity to store large amounts of arsenic aboveground

  20. Arsenic speciation in edible mushrooms.

    Science.gov (United States)

    Nearing, Michelle M; Koch, Iris; Reimer, Kenneth J

    2014-12-16

    The fruiting bodies, or mushrooms, of terrestrial fungi have been found to contain a high proportion of the nontoxic arsenic compound arsenobetaine (AB), but data gaps include a limited phylogenetic diversity of the fungi for which arsenic speciation is available, a focus on mushrooms with higher total arsenic concentrations, and the unknown formation and role of AB in mushrooms. To address these, the mushrooms of 46 different fungus species (73 samples) over a diverse range of phylogenetic groups were collected from Canadian grocery stores and background and arsenic-contaminated areas. Total arsenic was determined using ICP-MS, and arsenic speciation was determined using HPLC-ICP-MS and complementary X-ray absorption spectroscopy (XAS). The major arsenic compounds in mushrooms were found to be similar among phylogenetic groups, and AB was found to be the major compound in the Lycoperdaceae and Agaricaceae families but generally absent in log-growing mushrooms, suggesting the microbial community may influence arsenic speciation in mushrooms. The high proportion of AB in mushrooms with puffball or gilled morphologies may suggest that AB acts as an osmolyte in certain mushrooms to help maintain fruiting body structure. The presence of an As(III)-sulfur compound, for the first time in mushrooms, was identified in the XAS analysis. Except for Agaricus sp. (with predominantly AB), inorganic arsenic predominated in most of the store-bought mushrooms (albeit with low total arsenic concentrations). Should inorganic arsenic predominate in these mushrooms from contaminated areas, the risk to consumers under these circumstances should be considered.

  1. Molecular mechanisms of the antileukemia activities of retinoid and arsenic.

    Science.gov (United States)

    Nitto, Takeaki; Sawaki, Kohei

    2014-01-01

    Acute promyelocytic leukemia (APL) is characterized by the occurrence of translocations between chromosomes 15 and 17, resulting in generation of a fusion protein of promyelocytic leukemia (PML) and retinoid A receptor (RAR) α. APL cells are unable to differentiate into mature granulocytes since PML-RARα functions as a strong transcriptional repressor for a gene involved in granulocyte differentiation. All-trans retinoic acid (ATRA) is the first agent that has been developed to target specific disease-causing molecules, i.e., ATRA suppresses abnormal functions of oncogenic proteins. Moreover, ATRA facilitates the differentiation of APL cells toward mature granulocytes by changing epigenetic modifiers from corepressor complexes to co-activator complexes on target genes after binding to the ligand-binding domain at the RARα moiety of the PML-RARα oncoprotein. On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARα protein, causing oxidation and multimerization. ATO enhances the conjugation of small ubiquitin-like modifiers to PML-RARα, followed by ubiquitination and degradation, relieving the genes associated with granulocytic differentiation from suppressive restraint by the oncoprotein. Recent clinical studies have demonstrated that combination therapy with both ATRA and ATO is useful to achieve remission.

  2. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    Science.gov (United States)

    Exposure to inorganic arsenic remains a serious public health problem at many locations worldwide. If has often been noted that prevalences of signs and symptoms of chronic arsenic poisoning differ among various populations. For example, skin lesions or peripheral vascular dis...

  3. Arsenic Mobility and Groundwater Extraction in Bangladesh

    Science.gov (United States)

    Harvey, Charles F.; Swartz, Christopher H.; Badruzzaman, A. B. M.; Keon-Blute, Nicole; Yu, Winston; Ali, M. Ashraf; Jay, Jenny; Beckie, Roger; Niedan, Volker; Brabander, Daniel; Oates, Peter M.; Ashfaque, Khandaker N.; Islam, Shafiqul; Hemond, Harold F.; Ahmed, M. Feroze

    2002-11-01

    High levels of arsenic in well water are causing widespread poisoning in Bangladesh. In a typical aquifer in southern Bangladesh, chemical data imply that arsenic mobilization is associated with recent inflow of carbon. High concentrations of radiocarbon-young methane indicate that young carbon has driven recent biogeochemical processes, and irrigation pumping is sufficient to have drawn water to the depth where dissolved arsenic is at a maximum. The results of field injection of molasses, nitrate, and low-arsenic water show that organic carbon or its degradation products may quickly mobilize arsenic, oxidants may lower arsenic concentrations, and sorption of arsenic is limited by saturation of aquifer materials.

  4. Authentication of the 31 species of toxic and potent Chinese materia medica by microscopic technique assisted by ICP-MS analysis, part 4: four kinds of toxic and potent mineral arsenical CMMs.

    Science.gov (United States)

    Li, Qin; Chu, Chu; Wang, Ya-Qiong; Chen, Hu-Biao; Li, Ping; Zhao, Zhong-Zhen

    2011-01-01

    Toxic and Potent Chinese Materia Medica (T/PCMM) is a special and very important category of Chinese medicines. They have long been used in traditional medical practice and are being used more and more widely throughout the world in recent years. As there may be many fatal toxic effects caused by misusing or confusion of T/PCMM, their quality and safety control arouse increasing attention internationally. Researches on the accurate identification to ensure the safe use of T/PCMM are acquired; however, there are few reports on authentication. We are carrying out a series of studies on 31 T/PCMM originating from plants, animals, minerals, and secreta. In our previous studies, we proved that modern microscopic authentication is a simple, fast, effective, low cost, and less toxic method for identifying animal, seed, and flower T/PCMM. In the present study, we focused on the authentication of four kinds of mineral arsenicals, including orpiment (mainly containing As₂S₃), realgar (mainly containing As₄S₄), arsenolite, and arsenic trioxide (mainly containing As₂O₃). We examined the macroscopic and microscopic characteristics of the above minerals and found that they all can be easily identified and authenticated by using light microscopy coupled with polarized microscopy. Moreover, the authentication results for arsenolite and arsenic trioxide are confirmed by ICP-MS analysis. We are sure that the morphological and microscopic characteristics indicated here are indispensable to establishing standards for these four mineral T/PCMMs.

  5. Relativistic Multireference Quantum Chemical Study of the Electronic Structure of Actinide Trioxide Molecules.

    Science.gov (United States)

    Kovács, Attila

    2017-03-17

    Actinide trioxide (AnO3, An = U, Np, Pu, Am, Cm) molecules have been investigated by relativistic multireference quantum chemical calculations with the goal to elucidate their electronic structures. The molecular geometries of the ground and selected excited electronic states have been optimized at the spin-orbit-free complete active space second-order perturbation theory (SF-CASPT2) level. The low-lying vertical excitation states have been computed and characterized by CASPT2 calculations taking into account spin-orbit coupling. The reason for the considerable lengthening of the equatorial An-O bond in AmO3 and CmO3 with respect to the other trioxides has been analyzed on the basis of valence molecular orbitals of the SF ground electronic states. For the bond in question a singly occupied π orbital has been identified, this orbital is doubly occupied in the other (An = U, Np, Pu) trioxides. The clarified electronic structures of the investigated AnO3 molecules confirmed the pentavalent character of Am and Cm in their trioxides in contrast to the hexavalent character of U, Np, and Pu.

  6. 78 FR 59679 - Antimony Trioxide TSCA Chemical Risk Assessment; Notice of Public Meetings and Opportunity To...

    Science.gov (United States)

    2013-09-27

    ... Scientific Consulting Group (SCG), Inc., has identified a panel of scientific experts to conduct a peer... Chemical Risk Assessment for Antimony Trioxide.'' EPA will hold three peer review meetings by web connect... speakers providing oral comments during any or all of the peer review meetings as discussed in this...

  7. Use of a matrix for apexification procedure with mineral trioxide aggregate

    Directory of Open Access Journals (Sweden)

    Khatavkar Roheet

    2010-01-01

    Full Text Available This articles describes a technique for placement of a matrix barrier prior to use of mineral trioxide aggregate (MTA as an artificial root-end barrier. The technique also demonstrates the use of a delivery system utilizing large-bore needles for the predictable and precise placement of the barrier materials at the apex of the tooth.

  8. Arsenic transport by zebrafish aquaglyceroporins

    Directory of Open Access Journals (Sweden)

    Landfear Scott M

    2009-11-01

    Full Text Available Abstract Background Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (AsIII is one of the major species that exists environmentally. The transport of AsIII has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct AsIII and its organic metabolite, monomethylarsenite (MAsIII. However, the transport of AsIII and MAsIII in in any fish species has not been characterized. Results In this study, five members of the aquaglyceroporin family from zebrafish (Danio rerio were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (AsIII and MAsIII and antimonite (SbIII was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named aqp3, aqp3l, aqp9a, aqp9b and aqp10 according to their similarities to the corresponding human AQPs. Expression of aqp9a, aqp9b, aqp3, aqp3l and aqp10 in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from Xenopus leavis. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic AsIII, MAsIII and SbIII. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye

  9. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  10. Synergistic effect of radon and sodium arsenite on DNA damage in HBE cells.

    Science.gov (United States)

    Liu, Xing; Sun, Bin; Wang, Xiaojuan; Nie, Jihua; Chen, Zhihai; An, Yan; Tong, Jian

    2016-01-01

    Human epidemiological studies showed that radon and arsenic exposures are major risk factors for lung cancer in Yunnan tin miners. However, biological evidence for this phenomenon is absent. In this study, HBE cells were exposed to different concentrations of sodium arsenite, different radon exposure times, or a combination of these two factors. The results showed a synergistic effect of radon and sodium arsenite in cell cytotoxicity as determined by cell viability. Elevated intracellular ROS levels and increased DNA damage indexed by comet assay and γ-H2AX were detected. Moreover, DNA HR repair in terms of Rad51 declined when the cells were exposed to both radon and sodium arsenite. The synergistic effect of radon and sodium arsenite in HBE cells may be attributed to the enhanced DSBs and inhibited HR pathway upon co-exposure.

  11. Association between Chronic Arsenic Exposure and Nutritional Status among the Women of Child Bearing Age: A Case-Control Study in Bangladesh

    Directory of Open Access Journals (Sweden)

    Abul H. Milton

    2010-07-01

    Full Text Available The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 µg/L through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5 and 360 controls (BMI 18.5–24.99 were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant’s age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 µg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1–3.6 increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20–45 years.

  12. Arsenic toxicity to cladocerans isolated and associated with iron: implications for aquatic environments

    Directory of Open Access Journals (Sweden)

    SUELLEN C.M. SALES

    2016-01-01

    Full Text Available ABSTRACT Arsenic is an ametal ubiquitous in nature and known by its high toxicity. Many studies have tried to elucidate the arsenic metabolism in the cell and its impact to plants, animals and human health. In aqueous phase, inorganic arsenic is more common and its oxidation state (As III and As V depends on physical and chemical environmental conditions. The aim of this study was to evaluate toxicity of arsenic to Daphnia similis and Ceriodaphnia silvestrii, isolated and associated with iron. The results showed differences in toxicity of As III and As V to both species. Effective concentration (EC50 mean values were 0.45 mg L-1 (As III and 0.54 mg L-1 (As V for D. similis, and 0.44 mg L-1 (As III and 0.69 mg L-1 (As V for C. silvestrii. However, As V IC25 mean value was 0.59 mg L-1, indicating that C. silvestrii has mechanisms to reduce arsenic toxicity. On the other hand, when associated with iron at 0.02 and 2.00 mg L-1, EC50 values decreased for D. similis (0.34 and 0.38 mg L-1 as well as C. silvestrii (0.37 and 0.37 mg L-1, showing synergistic effect of these substances.

  13. Dynamic effects of autophagy on arsenic trioxide-induced death of human leukemia cell line HL60 cells

    Institute of Scientific and Technical Information of China (English)

    Ya-ping YANG; Zhong-qin LIANG; Bo GAO; Yan-li JIA; Zheng-hong QIN

    2008-01-01

    Aim: To evaluate the contribution of an autophagic mechanism to the As2O3-induced death of human acute myeloid leukaemia cell line HL60 cells. Methods: The growth inhibition of HL60 cells induced by As2O3 was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazohum bromide colorimetric assay. The ac-tivation of autophagy was determined with monodansylcadaverine labeling and transmission electron microscope. The role of autophagy in the As2O3-induced death of HL60 cells was assessed using autophagic and lysosomal inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms. Results: After treatment with As2O3, the proliferation of HL60 cells was significantly inhibited and the formation of autophagosomes increased. The blockade of autophagy maturation with the autophagy-specific inhibitor 3-methyladenine (3-MA) or the lysosome-neutraliz-ing agent NH4C11 h before As2O3 potentiated the As2O3-induced death of HL60 cells. In contrast, 3-MA attenuated As2O3-induced death when administered 30 min after As2O3. 3-MA and NH4Cl also inhibited As2O3-induced upregulation of microtubule-associated protein 1 light chain 3, the protein required for autophagy in mammalian cells. Following As2O3, lysosomes were activated as indicated by increased levels of cathepsins B and L. The apoptotic response of HL60 cells to As2O3 was suggested by the collapse of mitochondrial membrane potential, re-lease of cytochrome c from mitochondria, and the activation of caspase-3. Pre-treatment with 3-MA prior to As2O3 amplified these apoptotic signals, while post-treatment with 3-MA 30 min after As2O3 attenuated the apoptotic pathways. Conclusion: Autophagy plays complex roles in the As2O3-induced death of HL60 cells; it inhibits As2O3-induced apoptosis in the initiation stage, but amplifies the AS2O3-mediated apoptotic program if it is persistently activated.

  14. The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species

    Institute of Scientific and Technical Information of China (English)

    Fei GAO; Jing YI; Jing Qi YUAN; Gui Ying SHI; Xue Ming TANG

    2004-01-01

    Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry,with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI),indicated that As2O3 (2 μM) could induce apoptosis in NB4 cells prevailingly from G2/M phase,and this efficacy was enhanced upon co-administration of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (2.5 μM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determin the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.

  15. A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Ling He

    2016-01-01

    Full Text Available Primary hepatic carcinoma (PHC is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P<0.01, decreasing the value of alpha-fetoprotein (P<0.01, increasing the one-year survival rate (P<0.01, and improving the quality of life of PHC patients (P<0.01. Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed.

  16. Microbial responses to environmental arsenic.

    Science.gov (United States)

    Páez-Espino, David; Tamames, Javier; de Lorenzo, Víctor; Cánovas, David

    2009-02-01

    Microorganisms have evolved dynamic mechanisms for facing the toxicity of arsenic in the environment. In this sense, arsenic speciation and mobility is also affected by the microbial metabolism that participates in the biogeochemical cycle of the element. The ars operon constitutes the most ubiquitous and important scheme of arsenic tolerance in bacteria. This system mediates the extrusion of arsenite out of the cells. There are also other microbial activities that alter the chemical characteristics of arsenic: some strains are able to oxidize arsenite or reduce arsenate as part of their respiratory processes. These type of microorganisms require membrane associated proteins that transfer electrons from or to arsenic (AoxAB and ArrAB, respectively). Other enzymatic transformations, such as methylation-demethylation reactions, exchange inorganic arsenic into organic forms contributing to its complex environmental turnover. This short review highlights recent studies in ecology, biochemistry and molecular biology of these processes in bacteria, and also provides some examples of genetic engineering for enhanced arsenic accumulation based on phytochelatins or metallothionein-like proteins.

  17. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (parsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; parsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  18. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  19. 采用硫化砷渣制备三氧化二砷工艺%Preparation of arsenic trioxide from arsenic sulfide slag

    Institute of Scientific and Technical Information of China (English)

    郑雅杰; 刘万宇; 白猛; 张传福

    2008-01-01

    硫化砷渣经氢氧化钠溶液浸出、空气氧化脱硫和SO2还原制备得到As2O3.研究结果表明:当NaOH与As2S3物质的量比为7.2-1,固体质量与液体体积之比为1-6,反应温度为90 ℃,反应时间为2 h,转速为300 r/min时,用氢氧化钠溶液浸取硫化砷渣,其砷的浸取率达到95.90%;过滤后在碱浸液中通空气脱除碱浸液中Na3AsS3中的硫;当反应时间为10 h,反应温度为30 ℃,空气流量为120 L/h,对苯二酚和高锰酸钾质量浓度分别为1.5 g/L和0.5 g/L,木质素磺酸钠质量浓度为0.13 g/L时,脱硫率可达到96.00%;当pH值为0,反应时间为1 h,反应温度为30 ℃,砷质量浓度为60.00 g/L时通入SO2还原溶液中AsO43-,产物中As2O3含量和砷回收率分别达到92.14%和95.21%;稀硫酸洗涤后,As2O3纯度达95.14%.

  20. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  1. Discovery of the Arsenic Isotopes

    CERN Document Server

    Shore, A; Heim, M; Schuh, A; Thoennessen, M

    2009-01-01

    Twenty-nine arsenic isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  2. New Arsenic Cross Section Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Toshihiko [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-04

    This report presents calculations for the new arsenic cross section. Cross sections for 73,74,75 As above the resonance range were calculated with a newly developed Hauser-Feshbach code, CoH3.

  3. Arsenic Exposure and Prevalence of the Varicella Zoster Virus in the United States: NHANES (2003–2004 and 2009–2010)

    Science.gov (United States)

    Cardenas, Andres; Smit, Ellen; Houseman, E. Andres; Kerkvliet, Nancy I.; Bethel, Jeffrey W.

    2015-01-01

    Background Arsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide. Objective We evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S. population. Methods We analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2009–2010 pooled survey cycles. Participants were eligible if they were 6–49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine. Results The overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively. Conclusions In this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S. population. This finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms. Citation Cardenas A, Smit E, Houseman EA, Kerkvliet NI, Bethel JW, Kile ML. 2015. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003–2004 and 2009–2010). Environ Health Perspect 123:590–596;

  4. Arsenic removal by lime softening

    DEFF Research Database (Denmark)

    Kaosol, T.; Suksaroj, C.; Bregnhøj, Henrik

    2002-01-01

    This paper focuses on the study of arsenic removal for drinking water by lime softening. The initial arsenic (V) concentration was 500 and 1,000 ug/L in synthetic groundwater. The experiments were performed as batch tests with varying lime dosages and mixing time. For the synthetic groundwater......, arsenic (V) removal increased with increasing lime dosage and mixing time, as well as with the resulting pH. The residual arsenic (V) in all cases was lower than the WHO guideline of 10 ug/L at pH higher than 11.5. Kinetic of arsenic (V) removal can be described by a first-order equation as C1 = C0*e......^-k*t. The relation between the constant (k value) and increasing lime dosage was found to be linear, described by k = 0.0034 (Dlime). The results support a theory from the literature that the arsenic (V) was removed by precipitation af Ca3(AsO4)2. The results obtained in the present study suggest that lime...

  5. Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program

    Science.gov (United States)

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H.

    2013-01-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from…

  6. Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    Xiao Jing WANG; Jie YANG; Hui CANG; Yan Qiong ZOU; Jing YI

    2005-01-01

    Emodin (1,3,8-trihydroxy-6-methylanthraquinone) could enhance the sensitivity of tumor cells to arsenic trioxide (As2O3)-induced apoptosis via generation of ROS,but the molecular mechanism has not been elucidated.Here,we carried out cDNA microarray-based global transcription profiling of HeLa cells in response to As2O3/emodin cotreatment,comparing with As2O3-only treatment.The results showed that the expression of a number of genes was substantially altered at two time points.These genes are involved in different aspects of cell function.In addition to redox regulation and apoptosis,ROS affect genes encoding proteins associated with cell signaling,organelle functions,cell cycle,cytoskeleton,etc.These data suggest that based on the cytotoxicity of As2O3,emodin mobilize every genomic resource through which the As2O3-induced apoptosis is facilitated.

  7. Phytoremediation of arsenic contaminated soil by arsenic accumulators: a three year study.

    Science.gov (United States)

    Raj, Anshita; Singh, Nandita

    2015-03-01

    To investigate whether phytoremediation can remove arsenic from the contaminated area, a study was conducted for three consecutive years to determine the efficiency of Pteris vittata, Adiantum capillus veneris, Christella dentata and Phragmites karka, on arsenic removal from the arsenic contaminated soil. Arsenic concentrations in the soil samples were analysed after harvesting in 2009, 2010 and 2011 at an interval of 6 months. Frond arsenic concentrations were also estimated in all the successive harvests. Fronds resulted in the greatest amount of arsenic removal. Root arsenic concentrations were analysed in the last harvest. Approximately 70 % of arsenic was removed by P. vittata which was recorded as the highest among the four plant species. However, 60 % of arsenic was removed by A. capillus veneris, 55.1 % by C. dentata and 56.1 % by P. karka of arsenic was removed from the contaminated soil in 3 years.

  8. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species.

    Science.gov (United States)

    Norton, Gareth J; Adomako, Eureka E; Deacon, Claire M; Carey, Anne-Marie; Price, Adam H; Meharg, Andrew A

    2013-06-01

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic.

  9. Phytoextraction by arsenic hyperaccumulator Pteris vittata L. from six arsenic-contaminated soils: Repeated harvests and arsenic redistribution

    Energy Technology Data Exchange (ETDEWEB)

    Gonzaga, Maria I.S.; Santos, Jorge A.G. [Department of Soil Chemistry, Universidade Federal da Bahia, Cruz das Almas, 44380000 (Brazil); Ma, Lena Q. [Soil and Water Science Department, University of Florida, 2169 McCarty Hall, Gainesville, FL 32611-0290 (United States)], E-mail: lqma@ifas.ufl.edu

    2008-07-15

    This greenhouse experiment evaluated arsenic removal by Pteris vittata and its effects on arsenic redistribution in soils. P. vittata grew in six arsenic-contaminated soils and its fronds were harvested and analyzed for arsenic in October, 2003, April, 2004, and October, 2004. The soil arsenic was separated into five fractions via sequential extraction. The ferns grew well and took up arsenic from all soils. Fern biomass ranged from 24.8 to 33.5 g plant{sup -1} after 4 months of growth but was reduced in the subsequent harvests. The frond arsenic concentrations ranged from 66 to 6,151 mg kg{sup -1}, 110 to 3,056 mg kg{sup -1}, and 162 to 2,139 mg kg{sup -1} from the first, second and third harvest, respectively. P. vittata reduced soil arsenic by 6.4-13% after three harvests. Arsenic in the soils was primarily associated with amorphous hydrous oxides (40-59%), which contributed the most to arsenic taken up by P. vittata (45-72%). It is possible to use P. vittata to remediate arsenic-contaminated soils by repeatedly harvesting its fronds. - Pteris vittata was effective in continuously removing arsenic from contaminated soils after three repeated harvests.

  10. RARE CASE REPORT OF CHRONIC ARSENIC POISONING

    OpenAIRE

    Mundle; Neelima; Sushrut; Yogesh; Shukan; Shalik; Siddharth

    2014-01-01

    Today, arsenic is primarily used in the produc tion of glass and semiconductors., Arsenic may be found as a water or food contaminant, particularly in shellfish and other seafood, and often contaminates fruits and vegetables, particularly rice

  11. Inorganic arsenic poisoning in pastured feeder lambs

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, H.A.; Crane, M.R.; Tomson, K.

    1971-01-01

    Clinical signs and necropsy findings in a group of feeder lambs were suggestive of inorganic arsenic poisoning. Source of exposure was established and toxic concentrations of arsenic were detected in the tissues. 13 references, 1 table.

  12. RARE CASE REPORT OF CHRONIC ARSENIC POISONING

    Directory of Open Access Journals (Sweden)

    Mundle

    2014-12-01

    Full Text Available Today, arsenic is primarily used in the produc tion of glass and semiconductors., Arsenic may be found as a water or food contaminant, particularly in shellfish and other seafood, and often contaminates fruits and vegetables, particularly rice

  13. [Periapical regeneration. About one case of necrotic immature tooth treated with mineral trioxide aggregate (MTA)].

    Science.gov (United States)

    Dhaimy, S; Lahlou, K; Karami, M; Elmerini, H; Elouazzani, A

    2013-09-01

    Therapeutic of apexification with calcium hydroxide has been extensively used in clinical practice, but this technique has some drawbacks (long duration of treatment, weakening of the radicular walls). Different studies have proposed to close the apex opened with MTA (Mineral trioxide Aggregate) which is biocompatible, bacteriostatic, this material induces regeneration of the periapical region through the formation of cementum, bone and periodontal ligament (1, 2). This case report describes the technique of setting up in a single step of the Mineral trioxide Aggregate as an apical barrier for immature permanent roots. This method has allowed us an immediate apical sealing and a root canal filling and a coronary restore permanently as soon as possible. The radiological control confirmed that this type of apexification could be successful with periapical regeneration ad-integrum.

  14. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F. [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Chen, Yu [Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Rees, Judy R.; Zens, M. Scot [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Karagas, Margaret R., E-mail: margaret.r.karagas@dartmouth.edu [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  15. Insights into arsenic multi-operons expression and arsenic resistance mechanisms in Rhodopseudomonas palustris CGA009

    OpenAIRE

    Chungui eZhao; Yi eZhang; Zhuhua eChan; Shicheng eChen; Suping eYang

    2015-01-01

    Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2 and ars3) in R. palustris. In this study, we i...

  16. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  17. Success Rate of Formocresol Pulpotomy versus Mineral Trioxide Aggregate in Human Primary Molar Tooth

    Directory of Open Access Journals (Sweden)

    S E Jabbarifar

    2004-12-01

    Full Text Available Background: In spite of long time and broad use of formaldehyde derivates (Fixation agent in primary tooth pulp treatment, There is some concerns about these derivates such as variability, inconsistency success rate, mutagenicity, cytotoxicity, alergenicity, and some other potential health hazards of them. Therefore other alternative pulpotomy procedures like Bioactive glass (BAG, Glutaraldehyde (2%, Hydroxyappetite (HA, Bone dried freezed (BDF, ferric sulfate (15%, laser, Electrosurgery (ES, Bone Morphogenic proteins (BMP, recombinant protein-1 (RP1, and Mineral Trioxide Aggregate (MTA have been compared. The purpose of this clinical trial is to assess radiographic and clinical success rate of Formocresol (FC pulpotomy in compare with MTA in human primary molar teeth. Methods: 64 molars were pulpotomized equally and randomly with mineral trioxide Aggregate and Formocresol. Prior to trial, we defined a case as failure, when one or more of the events such as external root resorption, internal root resorption, periapical and furca lucency, pain, swelling, mobility, dental abscess, or early extraction appeared. Every treated tooth was defined as successful, if any noted evident was not shown. Results: Totally, 60 teeth treatment (92.2 percent were successful and 7.8 percent were failed. Failure and success rates for MTA group were 6.3 and 93.7 percent, respectively. Failure and success rates in FC group were 8.4 and 90.2 percent respectively. The difference between MTA and FC treatment methods was not significant (Fisher Exact test. Conclusion: Findings of this study show that mineral trioxide aggregate can be an alternative procedure for FC pulpotomy of primary tooth. Keywords: Mineral trioxide aggregate, formocresol, pulpotomy, success and failure rate.

  18. In vitro biocompatibility tests of two commercial types of mineral trioxide aggregate

    OpenAIRE

    Ribeiro,Daniel Araki; Matsumoto,Mariza Akemi; Marco Antonio Húngaro DUARTE; Marques, Mariangela Esther Alencar; Salvadori,Daisy Maria Favero

    2005-01-01

    Recently, regular and white mineral trioxide aggregate (MTA) are being used in Dentistry as retrofilling materials. Genotoxicity and cytotoxicity tests form an important part of cancer research and risk assessment of potential carcinogens. Thus, the goal of this study was to examine the genotoxicity and cytotoxicity of regular and white MTA in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Mouse lymphoma cells were exposed to two presentation forms of...

  19. Dissolution kinetics and thermodynamic analysis of vanadium trioxide during pressure oxidation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    The dissolution kinetics of vanadium trioxide in sulphuric acid-oxygen medium was examined. It was determined that the concentration of sulphuric acid and stirring speed above 800 r min 1 did not significantly affect vanadium extraction. The dissolution rate increased with increasing temperature and oxygen partial pressure, but decreased with increasing particle size. The dissolution kinetics was controlled by the chemical reaction at the surface with the estimated activation energy of 43.46 kJ·mol-1. The l...

  20. Optical characteristics of aerosol trioxide dialuminum at the IR wavelength range

    Science.gov (United States)

    Voitsekhovskaya, O. K.; Shefer, O. V.; Kashirskii, D. E.

    2015-11-01

    In this work, a numerical study of the transmission function, extinction coefficient, scattering coefficient, and absorption coefficient of the aerosol generated by the jet engine emissions was performed. Analyzing the calculation results of the IR optical characteristics of anthropogenic emissions containing the dialuminum trioxide was carried out. The spectral features of the optical characteristics of the medium caused by the average size, concentration and complex refractive index of the particles were illustrated.

  1. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Science.gov (United States)

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-01-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic’s effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. PMID:26048586

  2. Efficient photoelectrochemical hydrogen production from bismuth vanadate-decorated tungsten trioxide helix nanostructures

    Science.gov (United States)

    Shi, Xinjian; Choi, Il Yong; Zhang, Kan; Kwon, Jeong; Kim, Dong Yeong; Lee, Ja Kyung; Oh, Sang Ho; Kim, Jong Kyu; Park, Jong Hyeok

    2014-09-01

    Tungsten trioxide/bismuth vanadate heterojunction is one of the best pairs for solar water splitting, but its photocurrent densities are insufficient. Here we investigate the advantages of using helical nanostructures in photoelectrochemical solar water splitting. A helical tungsten trioxide array is fabricated on a fluorine-doped tin oxide substrate, followed by subsequent coating with bismuth vanadate/catalyst. A maximum photocurrent density of ~5.35±0.15 mA cm-2 is achieved at 1.23 V versus the reversible hydrogen electrode, and related hydrogen and oxygen evolution is also observed from this heterojunction. Theoretical simulations and analyses are performed to verify the advantages of this helical structure. The combination of effective light scattering, improved charge separation and transportation, and an enlarged contact surface area with electrolytes due to the use of the bismuth vanadate-decorated tungsten trioxide helical nanostructures leads to the highest reported photocurrent density to date at 1.23 V versus the reversible hydrogen electrode, to the best of our knowledge.

  3. Electrosprayed molybdenum trioxide aqueous solution and its application in organic photovoltaic cells.

    Science.gov (United States)

    Suzuki, Katsumi; Fukuda, Takeshi; Liao, Yingjie

    2014-01-01

    A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

  4. Electrosprayed molybdenum trioxide aqueous solution and its application in organic photovoltaic cells.

    Directory of Open Access Journals (Sweden)

    Katsumi Suzuki

    Full Text Available A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

  5. Synthesis and performance of bismuth trioxide nanoparticles for high energy gas generator use.

    Science.gov (United States)

    Martirosyan, K S; Wang, L; Vicent, A; Luss, D

    2009-10-01

    Our experiments showed that the combustion of an Al-Bi2O3 nanoparticle mixture generated the highest pressure pulse among common nanothermite reactions and can potentially be used as a nanoenergetic gas generator. The combustion front propagation velocity and rate of energy release increased by up to three orders of magnitude when the particle size was reduced to a nanosize range for both the aluminum and the oxidizer. We developed a novel one-step (metal nitrate-glycine) combustion synthesis of nanostructured amorphous-like and highly crystalline bismuth trioxide nanoparticles. The combustion synthesis was conducted using a solution of molten bismuth nitrate as an oxidizer and glycine as a fuel. The glycine was completely combusted during the thermal decomposition of the bismuth nitrate pentahydrate and generated a temperature front that propagated through the sample. Increasing the fuel concentration increased the maximum combustion temperature from 280 to 1200 degrees C and the Bi2O3 particle size from 20 to 100 nm. The oxidizer/fuel ratio had a strong impact on the bismuth trioxide particle crystallinity. At low temperature (280 degrees C), amorphous-like bismuth trioxide nanoparticles formed, while at T > or =370 degrees C the structures were crystalline. A peak pressure of approximately 12 MPa and a thermal front propagating velocity of approximately 2500 m s(-1) were achieved during the combustion of an Al-Bi2O3 mixture containing 80 wt% of the synthesized Bi2O3 crystalline nanoparticles (size: 40-50 nm).

  6. ARSENIC SEPARATION FROM WATER USING ZEOLITES

    Science.gov (United States)

    Arsenic is known to be a hazardous contaminant in drinking water. The presence of arsenic in water supplies has been linked to arsenical dermatosis and skin cancer . Zeolites are well known for their ion exchange capacities. In the present work, the potential use of a variety of ...

  7. Arsenic - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Arsenic URL of this page: https://medlineplus.gov/languages/arsenic.html Other topics A-Z A B C ... V W XYZ List of All Topics All Arsenic - Multiple Languages To use the sharing features on ...

  8. 21 CFR 556.60 - Arsenic.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND... New Animal Drugs § 556.60 Arsenic. Tolerances for total residues of combined arsenic (calculated as...

  9. Flourescence Humic Substances in Arsenic Contaminated Groundwater of Bangladesh

    Directory of Open Access Journals (Sweden)

    SHAFI M. TAREQ

    2012-06-01

    Full Text Available In the past, only arsenic (As concentrations in groundwater of Bangladesh were considered as having direct effects on the epidemical degrees of different types of diseases including arsenicosis, but the results of the present investigation indicated that fluorescence humic substance (HS is also an important component of dissolved organic matter in groundwater of Bangladesh. Therefore, it is suspected that both fluorescent HS and As in groundwater may have effects on the biological toxicity. The evidence of presence of high fluorescent HS and As in groundwater of Faridpur supports the above synergistic effect. The spatial distribution of fluorescence HS and As in groundwater of Faridpur indicated that the variations may be related to local hydrogeological conditions.

  10. Pyrolysis of waste electrical and electronic equipment: effect of antinomy trioxide on the pyrolysis of styrenic polymers.

    Science.gov (United States)

    Hall, W J; Bhaskar, T; Merpati, N M M; Muto, A; Sakata, Y; Williams, P T

    2007-09-01

    This work has investigated the effect that antimony trioxide has on the pyrolysis of styrenic polymers and the effect that different types of brominated flame retardants used in plastics have on the composition of the pyrolysis products. Brominated high impact polystyrene (Br-HIPS) which contained either 5% or 0% antimony trioxide and either decabromodiphenyl oxide (DDO) or decabromodiphenyl ethane (DDE) was pyrolysed in a fixed bed reactor at 430 degrees C. Some experiments on the fixed bed reactor involved mixing the Br-HIPS with polystyrene. The gaseous products were analysed by GC-FID and GC-TCD and it was found that antimony trioxide caused an increase in the proportion of ethane and ethene and suppressed the proportion of butane and butene. When DDE was the flame retardant increased proportions of ethane and ethene were found in the pyrolysis gas compared to when DDO used. When polystyrene was mixed with the Br-HIPS it suppressed the trends observed in the gas composition during the pyrolysis of Br-HIPS. The pyrolysis oils were characterised using FT-IR, GC-MS, GC-FID, and GC-ECD. It was found that the plastic which did not contain antimony trioxide pyrolysed to form mainly toluene, ethylbenzene, styrene, cumene, and alpha-methylstyrene. The oils produced from the pyrolysis of the plastic that contained antimony trioxide did not contain any styrene or alpha-methylstyrene, but instead contained greater concentrations of ethylbenzene and cumene. The absence of styrene and alpha-methylstyrene from the pyrolysis oil occurred even when the Br-HIPS was mixed with polystyrene. GC-ECD analysis of the oils showed that the plastics which did not contain antimony trioxide pyrolysed to form (1-bromoethyl)benzene, which was totally absent from the pyrolysis oils when antimony trioxide was present in the plastic.

  11. Arsenic removal by using colloidal adsorption flotation utilizing Fe(OH)3 floc in a dissolved air flotation system; Eliminacion de arsenico mediante flotacion por adsorcion coloidal utilizando floculos de Fe(OH){sub 3} en un sistema de flotacion por aire disuelto

    Energy Technology Data Exchange (ETDEWEB)

    Pavez, O.; Palacios, J. M.; Aguilar, C.

    2009-07-01

    In the present work, the influence of Fe/As ratio on the As removal, from aqueous solutions, applying flotation by colloidal adsorption was studied. Ferric chloride was used as coagulant and dodec il sulfate as collector, and arsenic trioxide was utilized to preparing the solutions. The obtained results show that the highest arsenic removal was accomplished in the range of pH between 4 and 5,5, and the increasing of the initial concentration of Fe(III), increases the removal of arsenic from the solution. However, with the decreasing of the initial concentration of arsenic in the solution, it is required a larger Fe/As ratio for its removal. For solutions containing: 13,73, 1,71 and 0,105 mg/L of arsenic, it was shown that to remove around 95% of the dissolved arsenic, a Fe/As ratios of approximately 6/1, 18/1 and 800/1, respectively, are required. (Author) 31 refs.

  12. Quantifying synergistic information remains an unsolved problem

    CERN Document Server

    Griffith, Virgil

    2011-01-01

    We review the prior literature of information theoretical measures of synergy or synergistic information. We draw the hereto unnamed conceptual distinction between synergistic and holistic information and analyze six prior measures based on whether they aim to quantify synergy or holism. We apply all measures against a suite of examples to demonstrate no existing measure correctly quantifies synergy under all circumstances.

  13. Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Ren, Dawei

    between plasmid host range and composition of the recipient community was investigated in Manuscript 5 by comparing plasmid permissiveness in single populations and in a microbial community composed of 15 soil strains. By use of flow cytometry (FCM) and 16S rRNA gene sequencing, the IncP1 plasmid, pKJK10...... bacterial species, the study to elucidate the impact of interaction networks on the multispecies biofilms in natural ecosystems, especially in soil, is still at an early stage. The diverse patterns of interactions within the mixed communities as well as the predatorprey relationship between protozoa...... interactions in this four-species biofilm model community. Manuscript 2 presents the further application of this developed approach on evaluating the synergistic/antagonistic interactions in multispecies biofilms composed of seven soil isolates. 63% of the four-species biofilms were found to interact...

  14. Arsenic – Poison or medicine?

    Directory of Open Access Journals (Sweden)

    Karolina Kulik-Kupka

    2016-04-01

    Full Text Available Arsenic (As is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine. Med Pr 2016;67(1:89–96

  15. Stress proteins induced by arsenic.

    Science.gov (United States)

    Del Razo, L M; Quintanilla-Vega, B; Brambila-Colombres, E; Calderón-Aranda, E S; Manno, M; Albores, A

    2001-12-01

    The elevated expression of stress proteins is considered to be a universal response to adverse conditions, representing a potential mechanism of cellular defense against disease and a potential target for novel therapeutics. Exposure to arsenicals either in vitro or in vivo in a variety of model systems has been shown to cause the induction of a number of the major stress protein families such as heat shock proteins (Hsp). Among them are members with low molecular weight, such as metallotionein and ubiquitin, as well as ones with masses of 27, 32, 60, 70, 90, and 110 kDa. In most of the cases, the induction of stress proteins depends on the capacity of the arsenical to reach the target, its valence, and the type of exposure, arsenite being the biggest inducer of most Hsp in several organs and systems. Hsp induction is a rapid dose-dependent response (1-8 h) to the acute exposure to arsenite. Thus, the stress response appears to be useful to monitor the sublethal toxicity resulting from a single exposure to arsenite. The present paper offers a critical review of the capacity of arsenicals to modulate the expression and/or accumulation of stress proteins. The physiological consequences of the arsenic-induced stress and its usefulness in monitoring effects resulting from arsenic exposure in humans and other organisms are discussed.

  16. 三氧化二砷和顺铂联用对乳腺癌裸鼠移植瘤生长抑制作用%Inhibition of combined application of arsenic trfoxide and cisplatin on the growth of MCF - 7 xenografted tumors in mude mice

    Institute of Scientific and Technical Information of China (English)

    温连英; 李海新

    2011-01-01

    Objective To study whether arsenic trioxide could potentiate the anti - tumor effect of cisplatin (DDP) on xenografted tumor growth of human breast cancer cell line MCF -7 in nude mice. Methods Human breast cancer cells ( MCF - 7 cells) were transplanted subcutaneously to BALB/C nude mice to generate tumors.Twenty- four nude mice bearing human breast cancer MCF -7 xenngrafted tumor were randomly divided into 4 groups,control group,arsenic trioxide group, cisplatin group and combination group. The model mice in four groups were respectively given 0.9% NaCl solution,3.0 mg/kg As2O3,0.2 mL once two days,3.0 mg/kg DDP,0. 2 mL twice a week,and combination of 1. 5 mg/kg As2O3 ,0. 2 mL once two days and 1. 5 mg/kg DDP,0. 2 mL twice a week. The tumor volumes and weight were measured respectively during the treatment. Tumor growth inhibition rate was calculated. Transmission electron microscopy was used to detect cellular ultrastructure of implanted tumor cells.Results The tumor weight and volume of the combination group were significantly different from those of other 3 groups ( P <0. 05). The nuclear fragmentation, ehromatin condensation and margination occurred in combination group. Conclusion Arsenic trioxide and cisplatin can significantly inhibit tumor growth in nude mice bearing human breast cancer cell line MCF -7 and their combination can produce a synergistic action.%目的 观察三氧化二砷(As2O3)和顺铂(DDP)联用对人乳腺癌细胞系MCF-7裸鼠移植瘤生长抑制有无增效作用.方法 建立裸鼠人乳腺癌MCF-7细胞移植瘤动物模型,成瘤后动物随机分为4组:对照组、As2O3组、DDP组、As2O3+DDP组.对照组予0.9%氯化钠注射液0.2 mL,隔日1次腹腔注射,共8次.As2O3组予As2O3 3.0 mg/kg,0.2 mL/次,隔日1次腹腔注射,共8次.DDP组予DDP 3.0 mg/kg,0.2 mL/次,每周2次腹腔注射,共4次.As2O3+DDP组予As2O3 1.5 mg/kg,0.2 mL/次,隔日1次腹腔注射,共8次;DDP 1.5 mg/kg,0.2 mL/次,每周2次腹腔注射,共4

  17. Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic.

    Science.gov (United States)

    Dickerson, Aisha S; Rahbar, Mohammad H; Bakian, Amanda V; Bilder, Deborah A; Harrington, Rebecca A; Pettygrove, Sydney; Kirby, Russell S; Durkin, Maureen S; Han, Inkyu; Moyé, Lemuel A; Pearson, Deborah A; Wingate, Martha Slay; Zahorodny, Walter M

    2016-07-01

    Lead, mercury, and arsenic are neurotoxicants with known effects on neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder apparent by early childhood. Using data on 4486 children with ASD residing in 2489 census tracts in five sites of the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring (ADDM) Network, we used multi-level negative binomial models to investigate if ambient lead, mercury, and arsenic concentrations, as measured by the US Environmental Protection Agency National-Scale Air Toxics Assessment (EPA-NATA), were associated with ASD prevalence. In unadjusted analyses, ambient metal concentrations were negatively associated with ASD prevalence. After adjusting for confounding factors, tracts with air concentrations of lead in the highest quartile had significantly higher ASD prevalence than tracts with lead concentrations in the lowest quartile (prevalence ratio (PR) = 1.36; 95 '% CI: 1.18, 1.57). In addition, tracts with mercury concentrations above the 75th percentile (>1.7 ng/m(3)) and arsenic concentrations below the 75th percentile (≤0.13 ng/m(3)) had a significantly higher ASD prevalence (adjusted RR = 1.20; 95 % CI: 1.03, 1.40) compared to tracts with arsenic, lead, and mercury concentrations below the 75th percentile. Our results suggest a possible association between ambient lead concentrations and ASD prevalence and demonstrate that exposure to multiple metals may have synergistic effects on ASD prevalence.

  18. When Parasites Are Good for Health: Cestode Parasitism Increases Resistance to Arsenic in Brine Shrimps.

    Directory of Open Access Journals (Sweden)

    Marta I Sánchez

    2016-03-01

    Full Text Available Parasites and pollutants can both affect any living organism, and their interactions can be very important. To date, repeated studies have found that parasites and heavy metals or metalloids both have important negative effects on the health of animals, often in a synergistic manner. Here, we show for the first time that parasites can increase host resistance to metalloid arsenic, focusing on a clonal population of brine shrimp from the contaminated Odiel and Tinto estuary in SW Spain. We studied the effect of cestodes on the response of Artemia to arsenic (acute toxicity tests, 24h LC50 and found that infection consistently reduced mortality across a range of arsenic concentrations. An increase from 25°C to 29°C, simulating the change in mean temperature expected under climate change, increased arsenic toxicity, but the benefits of infection persisted. Infected individuals showed higher levels of catalase and glutathione reductase activity, antioxidant enzymes with a very important role in the protection against oxidative stress. Levels of TBARS were unaffected by parasites, suggesting that infection is not associated with oxidative damage. Moreover, infected Artemia had a higher number of carotenoid-rich lipid droplets which may also protect the host through the "survival of the fattest" principle and the antioxidant potential of carotenoids. This study illustrates the need to consider the multi-stress context (contaminants and temperature increase in which host-parasite interactions occur.

  19. Mineral resource of the month: arsenic

    Science.gov (United States)

    Brooks, William E.

    2008-01-01

    Arsenic has a long and varied history: Although it was not isolated as an element until the 13th century, it was known to the ancient Chinese, Egyptians and Greeks in compound form in the minerals arsenopyrite, realgar and orpiment. In the 1400s, “Scheele’s Green” was first used as an arsenic pigment in wallpaper, and leached arsenic from wallpaper may have contributed to Napoleon’s death in 1821. The 1940s play and later movie, Arsenic and Old Lace, dramatizes the metal’s more sinister role. Arsenic continues to be an important mineral commodity with many modern applications.

  20. Arsenic mobility in contaminated lake sediments

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaidis, Nikolaos P.; Dobbs, Gregory M.; Chen, Jing; Lackovic, Jeffrey

    2004-06-01

    An arsenic contaminated lake sediment near a landfill in Maine was used to characterize the geochemistry of arsenic and assess the influence of environmental conditions on its mobility. A kinetic model was developed to simulate the leaching ability of arsenic in lake sediments under different environmental conditions. The HM1D chemical transport model was used to model the column experiments and determine the rates of arsenic mobility from the sediment. Laboratory studies provided the information to construct a conceptual model to demonstrate the mobility of arsenic in the lake sediment. The leaching ability of arsenic in lake sediments greatly depends on the flow conditions of ground water and the geochemistry of the sediments. Large amounts of arsenic were tightly bound to the sediments. The amount of arsenic leaching out of the sediment to the water column was substantially decreased due to iron/arsenic co-precipitation at the water-sediment interface. Overall, it was found that arsenic greatly accumulated at the ground water/lake interface and it formed insoluble precipitates. - Arsenic accumulates at the ground water/lake interface, where it forms insoluble precipitates.

  1. Arsenic-cadmium interaction in rats.

    Science.gov (United States)

    Díaz-Barriga, F; Llamas, E; Mejía, J J; Carrizales, L; Santoyo, M E; Vega-Vega, L; Yáñez, L

    1990-11-01

    Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.

  2. Speciation analysis of arsenic in groundwater from Inner Mongolia with an emphasis on acid-leachable particulate arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Gong Zhilong [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Lu Xiufen [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Watt, Corinna [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Wen Bei [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); He Bin [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada); Mumford, Judy [National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Human Studies Division, Epidemiology and Biomarkers Branch, Research Triangle Park, NC 27711 (United States); Ning Zhixiong [Ba Men Anti-Epidemic Station, Lin He, Inner Mongolia (China); Xia Yajuan [Inner Mongolia Center for Endemic Disease Control and Research, Huhhot, Inner Mongolia (China); Le, X. Chris [Department of Public Health Sciences, University of Alberta, 10-102 Clinical Sciences Building, Edmonton, Alta., T6G 2G3 (Canada)]. E-mail: xc.le@ualberta.ca

    2006-01-05

    Arsenic in drinking water affects millions of people around the world. While soluble arsenic is commonly measured, the amount of particulate arsenic in drinking water has often been overlooked. We report here determination of the acid-leachable particulate arsenic and soluble arsenicals in well water from an arsenic-poisoning endemic area in Inner Mongolia, China. Water samples (583) were collected from 120 wells in Ba Men, Inner Mongolia, where well water was the primary drinking water source. Two methods were demonstrated for the determination of soluble arsenic species (primarily inorganic arsenate and arsenite) and total particulate arsenic. The first method used solid phase extraction cartridges and membrane filters to separate arsenic species on-site, followed by analysis of the individual arsenic species eluted from the cartridges and filters. The other method uses liquid chromatography separation with hydride generation atomic fluorescence detection to determine soluble arsenic species. Analysis of acidified water samples using inductively coupled plasma mass spectrometry provided the total arsenic concentration. Arsenic concentrations in water samples from the 120 wells ranged from <1 to {approx}1000 {mu}g L{sup -1}. On average, particulate arsenic accounted for 39 {+-} 38% (median 36%) of the total arsenic. In some wells, particulate arsenic was six times higher than the soluble arsenic concentration. Particulate arsenic can be effectively removed using membrane filtration. The information on particulate and soluble arsenic in water is useful for optimizing treatment options and for understanding the geochemical behavior of arsenic in groundwater.

  3. Silica ecosystem for synergistic biotransformation

    Science.gov (United States)

    Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

    2016-06-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system.

  4. Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

    Directory of Open Access Journals (Sweden)

    Linsheng Yang

    2011-06-01

    Full Text Available In contrast to arsenic (As poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions, who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China, were reported. The urinary arsenic species, including inorganic arsenic (iAs [arsenite (iAsIII and arsenate (iAsV], monomethylarsonic acid (MMAV and dimethylarsinic acid (DMAV, were determined by high-performance liquid chromatography (HPLC combined with inductively coupled plasma mass spectroscopy (ICP-MS. The relative distributions of arsenic species, the primary methylation index (PMI = MMAV/iAs and the secondary methylation index (SMI = DMAV/MMAV were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  5. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J.; Zheng, B.S.; Aposhian, H.V.; Zhou, Y.S.; Chen, M.L.; Zhang, A.H.; Waalkes, M.P. [NIEHS, Research Triangle Park, NC (USA)

    2002-07-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China was investigated. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such over exposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  6. Flame-retardancy of a Cellulosic Fabric by the Application of Synergistic Effect between Ammonium Bromide and Antimony (Ⅲ)Oxide

    Institute of Scientific and Technical Information of China (English)

    MOSTASHARI Seyed Morteza; MOAFI Hadi Fallah

    2009-01-01

    The synergistic effect between ammonium bromide and antimony(Ⅲ) oxide as a nondurable finish on the flammability of 100% woven plain cotton fabric(with a density of 144 g/m2,the number of yarns 21 per 10 mm),has been investigated in this study. The laundered totally-dried, weighed specimens were impregnated with suitable concentration individual aqueous ammonium bromide and/or antimony (Ⅲ)oxide suspension solutions and some sets weIle impregnated with appropriate admixed solutions of the both chemicals.A vertical flame spread test Was then carried-out to characterize the flammability of the samples.An acceptable synergistic effect was then experi.enced by using an admixed bath containing 0.1 molar ammonium bromide and O.05 unit formal antimony trioxide solutions for impartation of flame.retardancy to a cotton fabric.The optimum mass of the mixture required to lm.Dart flame-retardancy was about 3.64 g of anhydrous additives per 100 g of fabric.The results obtained are in favor 0f Wall Effect Theory.Moreover synergistic eflfect indicating dehydration of the treated substrate by using this combination via thermogravimetry could be deduced.

  7. Methanogenic inhibition by arsenic compounds.

    Science.gov (United States)

    Sierra-Alvarez, Reyes; Cortinas, Irail; Yenal, Umur; Field, Jim A

    2004-09-01

    The acute acetoclastic methanogenic inhibition of several inorganic and organic arsenicals was assayed. Trivalent species, i.e., methylarsonous acid and arsenite, were highly inhibitory, with 50% inhibitory concentrations of 9.1 and 15.0 microM, respectively, whereas pentavalent species were generally nontoxic. The nitrophenylarsonate derivate, roxarsone, displayed moderate toxicity.

  8. Acute arsenic poisoning diagnosed late.

    Science.gov (United States)

    Shumy, Farzana; Anam, Ahmad Mursel; Kamruzzaman, A K M; Amin, Md Robed; Chowdhury, M A Jalil

    2016-04-01

    Acute arsenicosis, although having a 'historical' background, is not common in our times. This report describes a case of acute arsenic poisoning, missed initially due to its gastroenteritis-like presentation, but suspected and confirmed much later, when the patient sought medical help for delayed complications after about 2 months.

  9. The microbial genomics of arsenic.

    Science.gov (United States)

    Andres, Jérémy; Bertin, Philippe N

    2016-03-01

    Arsenic, which is a major contaminant of many aquatic ecosystems worldwide, is responsible for serious public health issues. However, life has evolved various strategies for coping with this toxic element. In particular, prokaryotic organisms have developed processes enabling them to resist and metabolize this chemical. Studies based on genome sequencing and transcriptome, proteome and metabolome profiling have greatly improved our knowledge of prokaryotes' metabolic potential and functioning in contaminated environments. The increasing number of genomes available and the development of descriptive and comparative approaches have made it possible not only to identify several genetic determinants of the arsenic metabolism, but also to elucidate their phylogenetic distribution and their modes of regulation. In addition, studies using functional genomic tools have established the pleiotropic character of prokaryotes' responses to arsenic, which can be either common to several species or species-specific. These approaches also provide promising means of deciphering the functioning of microbial communities including uncultured organisms, the genetic transfers involved and the possible occurrence of metabolic interactions as well as the evolution of arsenic resistance and metabolism.

  10. Sequestration of arsenic in ombrotrophic peatlands

    Science.gov (United States)

    Rothwell, James; Hudson-Edwards, Karen; Taylor, Kevin; Polya, David; Evans, Martin; Allott, Tim

    2014-05-01

    Peatlands can be important stores of arsenic but we are lacking spectroscopic evidence of the sequestration pathways of this toxic metalloid in peatland environments. This study reports on the solid-phase speciation of anthropogenically-derived arsenic in atmospherically contaminated peat from the Peak District National Park (UK). Surface and sub-surface peat samples were analysed by synchrotron X-ray absorption spectroscopy on B18 beamline at Diamond Light Source (UK). The results suggest that there are contrasting arsenic sequestration mechanisms in the peat. The bulk arsenic speciation results, in combination with strong arsenic-iron correlations at the surface, suggest that iron (hydr)oxides are key phases for the immobilisation of arsenic at the peat surface. In contrast, the deeper peat samples are dominated by arsenic sulphides (arsenopyrite, realgar and orpiment). Given that these peats receive inputs solely from the atmosphere, the presence of these sulphide phases suggests an in-situ authigenic formation. Redox oscillations in the peat due to a fluctuating water table and an abundant store of legacy sulphur from historic acid rain inputs may favour the precipitation of arsenic sequestering sulphides in sub-surface horizons. Oxidation-induced loss of these arsenic sequestering sulphur species by water table drawdown has important implications for the mobility of arsenic and the quality of waters draining peatlands.

  11. Arsenic chemistry in soils and sediments

    Energy Technology Data Exchange (ETDEWEB)

    Fendorf, S.; Nico, P.; Kocar, B.D.; Masue, Y.; Tufano, K.J.

    2009-10-15

    Arsenic is a naturally occurring trace element that poses a threat to human and ecosystem health, particularly when incorporated into food or water supplies. The greatest risk imposed by arsenic to human health results from contamination of drinking water, for which the World Health Organization recommends a maximum limit of 10 {micro}g L{sup -1}. Continued ingestion of drinking water having hazardous levels of arsenic can lead to arsenicosis and cancers of the bladder, skin, lungs and kidneys. Unfortunately, arsenic tainted drinking waters are a global threat and presently having a devastating impact on human health within Asia. Nearly 100 million people, for example, are presently consuming drinking water having arsenic concentrations exceeding the World Health Organization's recommended limit (Ahmed et al., 2006). Arsenic contamination of the environment often results from human activities such as mining or pesticide application, but recently natural sources of arsenic have demonstrated a devastating impact on water quality. Arsenic becomes problematic from a health perspective principally when it partitions into the aqueous rather than the solid phase. Dissolved concentrations, and the resulting mobility, of arsenic within soils and sediments are the combined result of biogeochemical processes linked to hydrologic factors. Processes favoring the partitioning of As into the aqueous phase, potentially leading to hazardous concentrations, vary extensively but can broadly be grouped into four categories: (1) ion displacement, (2) desorption (or limited sorption) at pH values > 8.5, (3) reduction of arsenate to arsenite, and (4) mineral dissolution, particularly reductive dissolution of Fe and Mn (hydr)oxides. Although various processes may liberate arsenic from solids, a transition from aerobic to anaerobic conditions, and commensurate arsenic and iron/manganese reduction, appears to be a dominant, but not exclusive, means by which high concentrations of

  12. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    Science.gov (United States)

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.Didecyldimethylammonium chloride [DDAC] was...

  13. Furcal-perforation repair with mineral trioxide aggregate: Two years follow-up

    Directory of Open Access Journals (Sweden)

    Emmanuel João Nogueira Leal da Silva

    2012-01-01

    Full Text Available Furcal perforations are significant iatrogenic complications of endodontic treatment and could lead to endodontic failure. Mineral trioxide aggregate (MTA has been regarded as an ideal material for perforation repair, retrograde filling, pulp capping, and apexification. This case report describes a furcal perforation in a maxillary first molar, which was repaired using MTA. The tooth was endodontically treated and coronally restored with resin composite. After 2 years, the absence of periradicular radiolucent lesions, pain, and swelling along with functional tooth stability indicated a successful outcome of sealing the perforation using MTA.

  14. White mineral trioxide aggregate pulpotomies: Two case reports with long-term follow-up

    Directory of Open Access Journals (Sweden)

    Sen Tunc Emine

    2011-01-01

    Full Text Available This case report describes the partial pulpotomy treatment of complicated crown fractures of two cases by using white mineral trioxide aggregate (WMTA with long-term follow-up. In the cases presented here, to injured incisor teeth were open apices and the pulp exposure site was large, so it was decided to perform vital pulpotomy with WMTA. Long-term follow-up examinations revealed that the treatment preserved pulpal vitality with continued root development and apex formation. WMTA may be considered as an alternative option for the treatment of traumatized immature permanent teeth.

  15. Electrodeposition-Based Fabrication and Characteristics of Tungsten Trioxide Thin Film

    OpenAIRE

    Li Lin; Chin-Pao Cheng; Tun-Ping Teng

    2016-01-01

    In this study, tungsten trioxide (WO3) thin films were electrodeposited on indium tin oxide (ITO) glass to form WO3-coated glass. The electrodeposition (ED) time (tED) and ED current (IED) were varied to control the film thickness and morphology. Furthermore, the crystallization of the thin films was controlled by annealing them at 250°C, 500°C, and 700°C. The results showed that the thickness of the WO3 thin films increased with tED and IED. The as-deposited thin films and those annealed at ...

  16. Obturating teeth with wide open apices using mineral trioxide aggregate: a case report.

    Science.gov (United States)

    Levenstein, H

    2002-07-01

    The conventional approach in handling a tooth with a wide open apex requiring endodontic treatment is by means of a procedure called apexification. The objective of treatment is to introduce calcium hydroxide mixed with sterile water or local anaesthetic into the root canal to create a hard-tissue-like formation or an apical plug to prevent extrusion of filling materials during obturation of teeth with wide open apices. This procedure may take anything from 6 months to 2 years. In 1999 a new material called mineral trioxide aggregate (MTA) was introduced to the dental profession for clinical use which has the ability to create an apical plug within a few weeks.

  17. The effect of variable environmental arsenic contamination on urinary concentrations of arsenic species.

    OpenAIRE

    Kalman, D A; Hughes, J; BELLE, G.; Burbacher, T; Bolgiano, D; Coble, K; Mottet, N. K.; Polissar, L

    1990-01-01

    Urinary arsenic species have been determined for approximately 3000 urine samples obtained from residents of a community surrounding an arsenic-emitting copper smelter. Levels of inorganic, monomethylated and dimethylated arsenic species ranged from less than 1 microgram/L (the instrumental detection limit) to 180 micrograms/L seen for dimethyl arsenic. Comparison of a subsample of this population that had the least environmental contamination with the subsample having highest environmental a...

  18. Arsenic adsorption of lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil

    OpenAIRE

    Wuthiphun, L.; Towatana, P.; Arrykul, S.; Chongsuvivatwong, V

    2007-01-01

    Arsenic adsorption efficiency of soil covering materials (lateritic soil, limestone powder, lime and fly ash) on arsenic-contaminated soil obtained from Ronpiboon District, Nakhon Sri Thammarat Province tosolve arsenic air pollution problem was investigated using batch experiments. The four types of the aforementioned soil covering materials were examined to determine their arsenic adsorption efficiency, equilibriumtime as well as adsorption isotherms.The results revealed that among soil cove...

  19. Mineral sources and transport pathways for arsenic release in a coastal watershed, USA

    Science.gov (United States)

    Foley, Nora K.; Ayuso, Robert A.

    2008-01-01

    Metasedimentary bedrock of coastal Maine contains a diverse suite of As-bearing minerals that act as significant sources of elements found in ground and surface waters in the region. Arsenic sources in the Penobscot Formation include, in order of decreasing As content by weight: löllingite and realgar (c.70%), arsenopyrite, cobaltite, glaucodot, and gersdorffite (in the range of 34–45%), arsenian pyrite ( glaucodot, arsenopyrite-cobaltian > arsenopyrite, cobaltite, gersdorffite, fine-grained pyrite, Ni-pyrite > coarse-grained pyrite. Reactions illustrate that oxidation of Fe-As disulphide group and As-sulphide minerals is the primary release process for As. Liberation of As by carbonation of realgar and orpiment in contact with high-pH groundwaters may contribute locally to elevated contents of As in groundwater, especially where As is decoupled from Fe. Released metals are sequestered in secondary minerals by sorption or by incorporation in crystal structures. Secondary minerals acting as intermediate As reservoirs include claudetite (c.75%), orpiment (61%), scorodite (c. 45%), secondary arsenopyrite (c. 46%), goethite (<4490 ppm), natrojarosite (<42 ppm), rosenite, melanterite, ferrihydrite, and Mn-hydroxide coatings. Some soils also contain Fe-Co-Ni-arsenate, Ca-arsenate, and carbonate minerals. Reductive dissolution of Fe-oxide minerals may govern the ultimate release of iron and arsenic – especially As(V) – to groundwater; however, dissolution of claudetite (arsenic trioxide) may directly contribute As(III). Processes thought to explain the release of As from minerals in bedrock include oxidation of arsenian pyrite or arsenopyrite, or carbonation of As-sulphides, and most models based on these generally rely on discrete minerals or on a fairly limited series of minerals. In contrast, in the Penobscot Formation and other metasedimentary rocks of coastal Maine, oxidation of As-bearing Fe-cobalt-nickel-sulphide minerals, dissolution (by reduction) of

  20. Outbreak of arsenic and toxaphene poisoning in Kenyan cattle. [Arsenic was detected in cattle dips

    Energy Technology Data Exchange (ETDEWEB)

    Maitai, C.K.; Kamau, J.A.; Gacuhi, D.M.; Njoroge, S.

    1975-02-15

    In a case of poisoning involving 70 cattle analysis of specimens obtained during post mortem examination showed that the toxic substances were arsenic and toxaphene. This was consistent with both the clinical and post mortem findings. Arsenic was detected in water from an abandoned cattle dip in the farm. Soil samples collected in the vicinity of the dip contained both arsenic and toxaphene.

  1. Method of arsenic removal from water

    Energy Technology Data Exchange (ETDEWEB)

    Gadgil, Ashok (El Cerrito, CA)

    2010-10-26

    A method for low-cost arsenic removal from drinking water using chemically prepared bottom ash pre-treated with ferrous sulfate and then sodium hydroxide. Deposits on the surface of particles of bottom ash form of activated iron adsorbent with a high affinity for arsenic. In laboratory tests, a miniscule 5 grams of pre-treated bottom ash was sufficient to remove the arsenic from 2 liters of 2400 ppb (parts per billion) arsenic-laden water to a level below 50 ppb (the present United States Environmental Protection Agency limit). By increasing the amount of pre-treated bottom ash, even lower levels of post-treatment arsenic are expected. It is further expected that this invention supplies a very low-cost solution to arsenic poisoning for large population segments.

  2. Arsenic geochemistry of groundwater in Southeast Asia.

    Science.gov (United States)

    Kim, Kyoung-Woong; Chanpiwat, Penradee; Hanh, Hoang Thi; Phan, Kongkea; Sthiannopkao, Suthipong

    2011-12-01

    The occurrence of high concentrations of arsenic in the groundwater of the Southeast Asia region has received much attention in the past decade. This study presents an overview of the arsenic contamination problems in Vietnam, Cambodia, Lao People's Democratic Republic and Thailand. Most groundwater used as a source of drinking water in rural areas has been found to be contaminated with arsenic exceeding the WHO drinking water guideline of 10 μg·L(-1). With the exception of Thailand, groundwater was found to be contaminated with naturally occurring arsenic in the region. Interestingly, high arsenic concentrations (> 10 μg·L(-1)) were generally found in the floodplain areas located along the Mekong River. The source of elevated arsenic concentrations in groundwater is thought to be the release of arsenic from river sediments under highly reducing conditions. In Thailand, arsenic has never been found naturally in groundwater, but originates from tin mining activities. More than 10 million residents in Southeast Asia are estimated to be at risk from consuming arsenic-contaminated groundwater. In Southeast Asia, groundwater has been found to be a significant source of daily inorganic arsenic intake in humans. A positive correlation between groundwater arsenic concentration and arsenic concentration in human hair has been observed in Cambodia and Vietnam. A substantial knowledge gap exists between the epidemiology of arsenicosis and its impact on human health. More collaborative studies particularly on the scope of public health and its epidemiology are needed to conduct to fulfill the knowledge gaps of As as well as to enhance the operational responses to As issue in Southeast Asian countries.

  3. Arsenic stress after the Proterozoic glaciations

    OpenAIRE

    Chi Fru, Ernest; Arvestål, Emma; Callac, Nolwenn; El Albani, Abderrazak; Kilias, Stephanos; Argyraki, Ariadne; Jakobsson, Martin

    2015-01-01

    Protection against arsenic damage in organisms positioned deep in the tree of life points to early evolutionary sensitization. Here, marine sedimentary records reveal a Proterozoic arsenic concentration patterned to glacial-interglacial ages. The low glacial and high interglacial sedimentary arsenic concentrations, suggest deteriorating habitable marine conditions may have coincided with atmospheric oxygen decline after ~2.1 billion years ago. A similar intensification of near continental mar...

  4. Presence of Arsenic in Commercial Beverages

    Directory of Open Access Journals (Sweden)

    Jason Roberge

    2009-01-01

    Full Text Available Problem statement: This study’s goal was to assess the arsenic concentration of various beverages and broths purchased from a local chain supermarket. A source of chronic arsenic exposure occurs via food and beverage consumption. Groundwater levels of total arsenic are regulated (-1 by the Environmental Protection Agency (EPA but few studies have examined arsenic concentrations in common beverages. Approach: In the initial analysis of 19 items, total arsenic concentration was assessed from a variety of fruit juices, sports drinks, sodas and broths. Items found to contain levels of total arsenic ≥5.0 µg L-1 were further evaluated. Additional analysis included purchasing multiple brands of items ≥5.0 µg L-1and analyzing them for total arsenic and chemical species of arsenic. Results: Among the beverages in the initial analysis, apple juice (10.79 µg L-1 and grape juice (49.87 µg L-1 contained the highest levels of total arsenic. Upon examination of items with As concentrations above 5.0 µg L-1, varying concentrations of total arsenic were found in apple cider (range: 5.41-15.27 µg L-1, apple juice (range: 10.67-22.35 µg L-1, baby fruit juice (range: 13.91-16.51 µg L-1 and grape juice (range: 17.69-47.59 µg L-1. Conclusion: Many commercially available juices contained concentrations of arsenic that were higher than the standard for total arsenic allowed in groundwater as set forth by the EPA. The concentration of As in these juices varied between and within brands. In general, those consuming apple and grape juices are the young and elderly and it is these populations that may be more vulnerable to over exposure of heavy metals.

  5. Arsenic and antimony transporters in eukaryotes.

    Science.gov (United States)

    Maciaszczyk-Dziubinska, Ewa; Wawrzycka, Donata; Wysocki, Robert

    2012-01-01

    Arsenic and antimony are toxic metalloids, naturally present in the environment and all organisms have developed pathways for their detoxification. The most effective metalloid tolerance systems in eukaryotes include downregulation of metalloid uptake, efflux out of the cell, and complexation with phytochelatin or glutathione followed by sequestration into the vacuole. Understanding of arsenic and antimony transport system is of high importance due to the increasing usage of arsenic-based drugs in the treatment of certain types of cancer and diseases caused by protozoan parasites as well as for the development of bio- and phytoremediation strategies for metalloid polluted areas. However, in contrast to prokaryotes, the knowledge about specific transporters of arsenic and antimony and the mechanisms of metalloid transport in eukaryotes has been very limited for a long time. Here, we review the recent advances in understanding of arsenic and antimony transport pathways in eukaryotes, including a dual role of aquaglyceroporins in uptake and efflux of metalloids, elucidation of arsenic transport mechanism by the yeast Acr3 transporter and its role in arsenic hyperaccumulation in ferns, identification of vacuolar transporters of arsenic-phytochelatin complexes in plants and forms of arsenic substrates recognized by mammalian ABC transporters.

  6. In-tank recirculating arsenic treatment system

    Science.gov (United States)

    Brady, Patrick V.; Dwyer, Brian P.; Krumhansl, James L.; Chwirka, Joseph D.

    2009-04-07

    A low-cost, water treatment system and method for reducing arsenic contamination in small community water storage tanks. Arsenic is removed by using a submersible pump, sitting at the bottom of the tank, which continuously recirculates (at a low flow rate) arsenic-contaminated water through an attached and enclosed filter bed containing arsenic-sorbing media. The pump and treatment column can be either placed inside the tank (In-Tank) by manually-lowering through an access hole, or attached to the outside of the tank (Out-of-Tank), for easy replacement of the sorption media.

  7. Certain cases of poisoning by arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Cristol, P.; Fourcade, J.; Ravoire, J.; Bezenech, C.

    1939-05-01

    Cases of acute and chronic poisoning by arsenic are reported. Diffuse pains, angor, edema of the limbs and genitals, complicated by heptic insufficiency and chronic bronchitis were determined in a subject having lived near an industrial plant processing arseniferous ores for several years. The plant emitted several hundred kg of finely dispersed arsenic oxide daily which settled on forage and vegetables. Symptoms of poisoning by arsenic were also detected in cattle in the same area. The installation of Cottrell type dust separators has helped to suppress the arsenic oxide emissions.

  8. Arsenic-bound excitons in diamond

    Science.gov (United States)

    Barjon, J.; Jomard, F.; Morata, S.

    2014-01-01

    A set of new excitonic recombinations is observed in arsenic-implanted diamond. It is composed of two groups of emissions at 5.355/5.361 eV and at 5.215/5.220/5.227 eV. They are respectively attributed to the no-phonon and transverse-optical phonon-assisted recombinations of excitons bound to neutral arsenic donors. From the Haynes rule, an ionization energy of 0.41 eV is deduced for arsenic in diamond, which shows that arsenic is a shallower donor than phosphorus (0.6 eV), in agreement with theory.

  9. Arsenic speciation and sorption in natural environments

    Science.gov (United States)

    Campbell, Kate M.; Nordstrom, D. Kirk

    2014-01-01

    Aqueous arsenic speciation, or the chemical forms in which arsenic exists in water, is a challenging, interesting, and complicated aspect of environmental arsenic geochemistry. Arsenic has the ability to form a wide range of chemical bonds with carbon, oxygen, hydrogen, and sulfur, resulting in a large variety of compounds that exhibit a host of chemical and biochemical properties. Besides the intriguing chemical diversity, arsenic also has the rare capacity to capture our imaginations in a way that few elements can duplicate: it invokes images of foul play that range from sinister to comedic (e.g., “inheritance powder” and arsenic-spiked elderberry wine). However, the emergence of serious large-scale human health problems from chronic arsenic exposure in drinking water has placed a high priority on understanding environmental arsenic mobility, toxicity, and bioavailability, and chemical speciation is key to these important questions. Ultimately, the purpose of arsenic speciation research is to predict future occurrences, mitigate contamination, and provide successful management of water resources.

  10. Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

    Science.gov (United States)

    Rivera-Núñez, Zorimar; Meliker, Jaymie R; Meeker, John D; Slotnick, Melissa J; Nriagu, Jerome O

    2012-01-01

    The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (Pwater were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, Pwater was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

  11. The nature of chemical bond in trioxide Mi-UO3

    Directory of Open Access Journals (Sweden)

    Teterin Yury A.

    2002-01-01

    Full Text Available Low-energy X-ray photoelectron and conversion electron spectra from uranium trioxide were measured, and calculations were done for the [UO2O4]-6 (D4b cluster which reflects the structure of uranium close environment in MI-UO3 in the non-relativistic and relativistic Xa-DVM approximation. This enabled a satisfactory qualitative and in some cases quantitative agreement between the experimental and theoretical data, and interpretation of such spectra. Despite the traditional opinion that before participation in the chemical binding, the U5f electrons could be promoted to the higher (for example - U6d levels, it was theoretically proved and experimentally confirmed that the U5f electrons (about two U5f electrons are able to participate directly in the chemical bond formation in uranium trioxide. The filled U5f states proved to be localized in the outer valence molecular orbitals energy range 4-9 eV, while the vacant U5f states were generally localized in the low-energy range (0-6 eV above zero. It was experimentally shown that U6p electrons not only participate effectively in the inner valence molecular orbital formation but also participate strongly (more than 1 U6p electron in the formation of die filled outer valence molecular orbitals.

  12. Direct Hydrothermal Precipitation of Pyrochlore-Type Tungsten Trioxide Hemihydrate from Alkaline Sodium Tungstate Solution

    Science.gov (United States)

    Li, Xiaobin; Li, Jianpu; Zhou, Qiusheng; Peng, Zhihong; Liu, Guihua; Qi, Tiangui

    2012-04-01

    Pyrochlore-type tungsten trioxide hemihydrate (WO3·0.5H2O) powder with the average particle size of 0.5 μm was prepared successfully from the weak alkaline sodium tungstate solution by using organic substances of sucrose or cisbutenedioic acid as the acidification agent. The influences of solution pH and acidification agents on the precipitation process were investigated. The results showed that organic acidification agents such as sucrose and cisbutenedioic acid could improve the precipitation of pyrochlore WO3·0.5H2O greatly from sodium tungstate solution compared with the traditional acidification agent of hydrochloric acid. In addition, the pH value of the hydrothermal system played a critical role in the precipitation process of WO3·0.5H2O, and WO3·0.5H2O precipitation mainly occured in the pH range of 7.0 to 8.5. The precipitation rate of tungsten species in the sodium tungstate solution could reach up to 98 pct under the optimized hydrothermal conditions. This article proposed also the hydrothermal precipitation mechanism of WO3·0.5H2O from the weak alkaline sodium tungstate solution. The novel method reported in this study has a great potential to improve the efficiency of advanced tungsten trioxide-based functional material preparation, as well as for the pollution-reducing and energy-saving tungsten extractive metallurgy.

  13. [Tracing for arsenic exposure--a differentiation of arsenic compounds is essential for the health assessment].

    Science.gov (United States)

    Weistenhöfer, Wobbeke; Ochsmann, Elke; Drexler, Hans; Göen, Thomas; Klotz, Katrin

    2016-01-01

    Arsenic is ubiquitous and harmful to health in occupation and environment. Arsenic exposure is measured through analysis of arsenic compounds in urine. The identification of several arsenic species is necessary to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. To estimate the extent of an occupational exposure to arsenic, arsenic species were evaluated for the first time by the working group "Setting of Threshold Limit Values in Biological Material" of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area and Biologische Arbeitsstoffreferenzwerte (BAR) of 0.5 μg / L urine for arsenic (III), 0.5 μg / L urine for arsenic (V), 2 μg / L urine for monomethylarsonic acid (MMA) and 10 μg / L urine for dimethylarsinic acid (DMA) were set. If the reference value for total arsenic is exceeded, a further differentiation of arsenic species now enables to estimate the individual health risks taking into account special influences such as seafood consumption.

  14. Chromosome analysis of arsenic affected cattle

    Directory of Open Access Journals (Sweden)

    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  15. Interactions between arsenic species and marine algae

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, J.G.

    1978-01-01

    The arsenic concentration and speciation of marine algae varies widely, from 0.4 to 23 ng.mg/sup -1/, with significant differences in both total arsenic content and arsenic speciation occurring between algal classes. The Phaeophyceae contain more arsenic than other algal classes, and a greater proportion of the arsenic is organic. The concentration of inorganic arsenic is fairly constant in macro-algae, and may indicate a maximum level, with the excess being reduced and methylated. Phytoplankton take up As(V) readily, and incorporate a small percentage of it into the cell. The majority of the As(V) is reduced, methylated, and released to the surrounding media. The arsenic speciation in phytoplankton and Valonia also changes when As(V) is added to cultures. Arsenate and phosphate compete for uptake by algal cells. Arsenate inhibits primary production at concentrations as low as 5 ..mu..g.1/sup -1/ when the phosphate concentration is low. The inhibition is competitive. A phosphate enrichment of > 0.3 ..mu..M alleviates this inhibition; however, the As(V) stress causes an increase in the cell's phosphorus requirement. Arsenite is also toxic to phytoplankton at similar concentrations. Methylated arsenic species did not affect cell productivity, even at concentrations of 25 ..mu..g.1/sup -1/. Thus, the methylation of As(V) by the cell produces a stable, non-reactive compound which is nontoxic. The uptake and subsequent reduction and methylation of As(V) is a significant factor in determining the arsenic biogeochemistry of productive systems, and also the effect that the arsenic may have on algal productivity. Therefore, the role of marine algae in determining the arsenic speciation of marine systems cannot be ignored. (ERB)

  16. Arsenic Removal by Liquid Membranes

    Directory of Open Access Journals (Sweden)

    Tiziana Marino

    2015-03-01

    Full Text Available Water contamination with harmful arsenic compounds represents one of the most serious calamities of the last two centuries. Natural occurrence of the toxic metal has been revealed recently for 21 countries worldwide; the risk of arsenic intoxication is particularly high in Bangladesh and India but recently also Europe is facing similar problem. Liquid membranes (LMs look like a promising alternative to the existing removal processes, showing numerous advantages in terms of energy consumption, efficiency, selectivity, and operational costs. The development of different LM configurations has been a matter of investigation by several researching groups, especially for the removal of As(III and As(V from aqueous solutions. Most of these LM systems are based on the use of phosphine oxides as carriers, when the metal removal is from sulfuric acid media. Particularly promising for water treatment is the hollow fiber supported liquid membrane (HFSLM configuration, which offers high selectivity, easy transport of the targeted metal ions, large surface area, and non-stop flow process. The choice of organic extractant(s plays an essential role in the efficiency of the arsenic removal. Emulsion liquid membrane (ELM systems have not been extensively investigated so far, although encouraging results have started to appear in the literature. For such LM configuration, the most relevant step toward efficiency is the choice of the surfactant type and its concentration.

  17. SENSITIVITY OF LEUKEMIC CELL LINE HL-60 TO COMBINATION OF NEFERINE AND ARSENIC

    Institute of Scientific and Technical Information of China (English)

    LIU Ge-xiu; ZHANG Yuan; HE Dong-mei

    2006-01-01

    Objective: To determine whether neferine (Nef) enhances the sensitivity of human myeloid leukemia HL-60 cells to arsenic trioxide (ATO). Methods: Apoptosis was detected by DNA electrophoresis. Giemsa staining was used to observe the apoptotic cells under microscope. The apoptotic rates of cells were analyzed using flow cytometry. The inhibitory rates of cell growth were assayed by MTT, and the expression of P-gp was determined by flow cytometry. Results: Low doses of ATO (1.0 (mol/L) only partially inhibitory percentage of cell growth at 72 h was (9.92(3.03) % (P>0.05, vs control). The combination of 1.0 (mol/L ATO with 2.0 (mol/L Nef inhibited (45.27(4.93) % of cell growth, and induced apoptosis in leukemic cells more significantly than wither ATO or Nef on their own (P<0.01). Moreover, ATO-induced expression of P-gp in leukemic cells was inhibited significantly by Nef. Conclusion: These results indicate that Nef significantly increases sensitivity of leukemic cells to ATO, which might be associated with inhibitory expression of P-gp gene. Combined use of the two agents could be a novel and attractive strategy in leukemia treatment.

  18. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

    Science.gov (United States)

    Liu, Jie; Zheng, Baoshan; Aposhian, H Vasken; Zhou, Yunshu; Chen, Ming-Liang; Zhang, Aihua; Waalkes, Michael P

    2002-02-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  19. Bioaccumulation of Arsenic by Fungi

    Directory of Open Access Journals (Sweden)

    Ademola O. Adeyemi

    2009-01-01

    Full Text Available Problem statement: Arsenic is a known toxic element and its presence and toxicity in nature is a worldwide environmental problem. The use of microorganisms in bioremediation is a potential method to reduce as concentration in contaminated areas. Approach: In order to explore the possible bioremediation of this element, three filamentous fungi-Aspergillus niger, Serpula himantioides and Trametes versicolor were investigated for their potential abilities to accumulate (and possibly solubilize arsenic from an agar environment consisting of non buffered mineral salts media amended with 0.2, 0.4, 0.6 and 0.8% (w/v arsenopyrite (FeAsS. Growth rates, dry weights, arsenic accumulation and oxalate production by the fungi as well as the pH of the growth media were all assessed during this study. Results: There was no visible solubilization of FeAsS particles underneath any of the growing fungal colonies or elsewhere in the respective agar plates. No specific patterns of growth changes were observed from the growth ratios of the fungi on agar amended with different amounts of FeAsS although growth of all fungi was stimulated by the incorporation of varying amounts of FeAsS into the agar with the exception of A. niger on 0.4% (w/v amended agar and T. versicolor on 0.8% (w/v amended agar. The amounts of dry weights obtained for all three fungi also did not follow any specific patterns with different amounts of FeAsS and the quantities obtained were in the order A. niger > S. himantioides > T. versicolor. All fungi accumulated as in their biomasses with all amounts of FeAsS although to varying levels and T. versicolor was the most effective with all amounts of FeAsS while A. niger was the least effective. Conclusion: The accumulation of arsenic in the biomasses of the test fungi as shown in this study may suggested a role for fungi through their bioaccumulating capabilities as agents in the possible bioremediation of arsenic contaminated environments.

  20. Biotechnology based processes for arsenic removal

    NARCIS (Netherlands)

    Huisman, J.; Olde Weghuis, M.; Gonzalez-Contreras, P.A.

    2011-01-01

    The regulations for arsenic control have become strict. Therefore, better technologies to remove arsenic from bleeds and effluents are desired. In addition, no single solution is suitable for all cases. The properties of the process streams and the storage facilities are major factors determining th

  1. 29 CFR 1926.1118 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  2. 29 CFR 1915.1018 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  3. 29 CFR 1910.1018 - Inorganic arsenic.

    Science.gov (United States)

    2010-07-01

    ...) Engineering plans and studies used to determine methods selected for controlling exposure to inorganic arsenic... such exposures. The following three sections quoted from “Occupational Diseases: A Guide to Their.... Arsenic; chronic human intoxication. J. Occup. Med. 2:137. Elkins, H. B. 1959. The Chemistry of...

  4. Hijacking membrane transporters for arsenic phytoextraction.

    Science.gov (United States)

    LeBlanc, Melissa S; McKinney, Elizabeth C; Meagher, Richard B; Smith, Aaron P

    2013-01-10

    Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator.

  5. Arsenic and human health effects: A review.

    Science.gov (United States)

    Abdul, Khaja Shameem Mohammed; Jayasinghe, Sudheera Sammanthi; Chandana, Ediriweera P S; Jayasumana, Channa; De Silva, P Mangala C S

    2015-11-01

    Arsenic (As) is ubiquitous in nature and humans being exposed to arsenic via atmospheric air, ground water and food sources are certain. Major sources of arsenic contamination could be either through geological or via anthropogenic activities. In physiological individuals, organ system is described as group of organs that transact collectively and associate with other systems for conventional body functions. Arsenic has been associated with persuading a variety of complications in body organ systems: integumentary, nervous, respiratory, cardiovascular, hematopoietic, immune, endocrine, hepatic, renal, reproductive system and development. In this review, we outline the effects of arsenic on the human body with a main focus on assorted organ systems with respective disease conditions. Additionally, underlying mechanisms of disease development in each organ system due to arsenic have also been explored. Strikingly, arsenic has been able to induce epigenetic changes (in utero) and genetic mutations (a leading cause of cancer) in the body. Occurrence of various arsenic induced health effects involving emerging areas such as epigenetics and cancer along with their respective mechanisms are also briefly discussed.

  6. ARSENIC EFFECTS ON TELOMERE AND TELOMERASE ACTIVITY

    Science.gov (United States)

    Arsenic effects on telomere and telomerase activity. T-C. Zhang, M. T. Schmitt, J. Mo, J. L. Mumford, National Research Council and U.S Environmental Protection Agency, NHEERL, Research Triangle Park, NC 27711Arsenic is a known carcinogen and also an anticancer agent for acut...

  7. Arsenic pesticides and environmental pollution: exposure, poisoning, hazards and recommendations.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Mohammad, Amina El-Hosini; Morsy, Tosson A

    2013-08-01

    Arsenic is a metalloid element. Acute high-dose exposure to arsenic can cause severe systemic toxicity and death. Lower dose chronic arsenic exposure can result in subacute toxicity that can include peripheral sensorimotor neuropathy, skin eruptions, and hepatotoxicity. Long-term effects of arsenic exposure include an in Due to the physiologic effects of the arsenic on all body systems, thus, chronic arsenic-poisoned patient is a major nursing challenge. The critical care nurse provides valuable assessment and interventions that prevent major multisystem complications from arsenic toxicity.

  8. Arsenic Uptake by Muskmelon (Cucumis melo) Plants from Contaminated Water.

    Science.gov (United States)

    Hettick, Bryan E; Cañas-Carrell, Jaclyn E; Martin, Kirt; French, Amanda D; Klein, David M

    2016-09-01

    Arsenic is a carcinogenic element that occurs naturally in the environment. High levels of arsenic are found in water in some parts of the world, including Texas. The aims of this study were to determine the distribution of arsenic in muskmelon (Cucumis melo) plants accumulated from arsenic spiked water and to observe effects on plant biomass. Plants were grown and irrigated using water spiked with variable concentrations of arsenic. Inductively coupled plasma mass spectrometry was used to quantify arsenic in different parts of the plant and fruit. Under all conditions tested in this study, the highest concentrations of arsenic were found in the leaves, soil, and roots. Arsenic in the water had no significant effect on plant biomass. Fruits analyzed in this study had arsenic concentrations of 101 μg/kg or less. Consuming these fruits would result in less arsenic exposure than drinking water at recommended levels.

  9. Arsenic burden survey among refuse incinerator workers

    Directory of Open Access Journals (Sweden)

    Chao Chung-Liang

    2005-01-01

    Full Text Available Background: Incinerator workers are not considered to have arsenic overexposure although they have the risk of overexposure to other heavy metals. Aim: To examine the relationship between arsenic burden and risk of occupational exposure in employees working at a municipal refuse incinerator by determining the concentrations of arsenic in the blood and urine. Settings and Design: The workers were divided into three groups based on their probability of contact with combustion-generated residues, namely Group 1: indirect contact, Group 2: direct contact and Group 3: no contact. Healthy age- and sex-matched residents living in the vicinity were enrolled as the control group. Materials and Methods: Heavy metal concentrations were measured by atomic absorption spectrophotometer. Downstream rivers and drinking water of the residents were examined for environmental arsenic pollution. A questionnaire survey concerning the contact history of arsenic was simultaneously conducted. Statistical analysis: Non-parametric tests, cross-tabulation and multinomial logistic regression. Results: This study recruited 122 incinerator workers. The urine and blood arsenic concentrations as well as incidences of overexposure were significantly higher in the workers than in control subjects. The workers who had indirect or no contact with combustion-generated residues had significantly higher blood arsenic level. Arsenic contact history could not explain the difference. Airborne and waterborne arsenic pollution were not detected. Conclusion: Incinerator workers run the risk of being exposed to arsenic pollution, especially those who have incomplete protection in the workplace even though they only have indirect or no contact with combustion-generated pollutants.

  10. Both Phosphorus Fertilizers and Indigenous Bacteria Enhance Arsenic Release into Groundwater in Arsenic-Contaminated Aquifers.

    Science.gov (United States)

    Lin, Tzu-Yu; Wei, Chia-Cheng; Huang, Chi-Wei; Chang, Chun-Han; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2016-03-23

    Arsenic (As) is a human carcinogen, and arsenic contamination in groundwater is a worldwide public health concern. Arsenic-affected areas are found in many places but are reported mostly in agricultural farmlands, yet the interaction of fertilizers, microorganisms, and arsenic mobilization in arsenic-contaminated aquifers remains uncharacterized. This study investigates the effects of fertilizers and bacteria on the mobilization of arsenic in two arsenic-contaminated aquifers. We performed microcosm experiments using arsenic-contaminated sediments and amended with inorganic nitrogenous or phosphorus fertilizers for 1 and 4 months under aerobic and anaerobic conditions. The results show that microcosms amended with 100 mg/L phosphorus fertilizers (dipotassium phosphate), but not nitrogenous fertilizers (ammonium sulfate), significantly increase aqueous As(III) release in arsenic-contaminated sediments under anaerobic condition. We also show that concentrations of iron, manganese, potassium, sodium, calcium, and magnesium are increased in the aqueous phase and that the addition of dipotassium phosphate causes a further increase in aqueous iron, potassium, and sodium, suggesting that multiple metal elements may take part in the arsenic release process. Furthermore, microbial analysis indicates that the dominant microbial phylum is shifted from α-proteobacteria to β- and γ-proteobacteria when the As(III) is increased and phosphate is added in the aquifer. Our results provide evidence that both phosphorus fertilizers and microorganisms can mediate the release of arsenic to groundwater in arsenic-contaminated sediments under anaerobic condition. Our study suggests that agricultural activity such as the use of fertilizers and monitoring phosphate concentration in groundwater should be taken into consideration for the management of arsenic in groundwater.

  11. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Hui Shen

    2016-02-01

    Full Text Available Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001 following arsenic exposure: inorganic arsenic (iAs, monomethyl arsenic (MMA, dimethyl arsenic (DMA, and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD: 1.00; 95% confidence interval (CI: 0.60–1.40; p< 0.00001 and MMA (SMD: 0.49; 95% CI: 0.21–0.77; p = 0.0006 also increase, while the percentage of DMA (SMD: −0.57; 95% CI: −0.80–−0.31; p< 0.0001, primary methylation index (SMD: −0.57; 95% CI: −0.94–−0.20; p = 0.002, and secondary methylation index (SMD: −0.27; 95% CI: −0.46–−0.90; p = 0.004 decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  12. Evaluation of Exposure to Arsenic in Residential Soil

    OpenAIRE

    Tsuji, JS; Van Kerkhove, MD; Kaetzel, RS; Scrafford, CG; Mink, PJ; Barraj, LM; Crecelius, EA; Goodman, M.

    2005-01-01

    In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between...

  13. Synergistic effects in mixed Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Holler, B.M.; Molin, Søren

    2006-01-01

    the pathways governing development of more complex heterogeneous communities. In this study, we established a laboratory model where biofilm-stimulating effects due to interactions between genetically diverse strains of Escherichia coli were monitored. Synergistic induction of biofilm formation resulting from...

  14. Modelling synergistic effects of appetite regulating hormones

    DEFF Research Database (Denmark)

    Schmidt, Julie Berg; Ritz, Christian

    2016-01-01

    We briefly reviewed one definition of dose addition, which is applicable within the framework of generalized linear models. We established how this definition of dose addition corresponds to effect addition in case only two doses per compound are considered for evaluating synergistic effects. The....... The link between definitions was exemplified for an appetite study where two appetite hormones were studied....

  15. Cellular distribution of arsenic and other elements in hyperaccumulator Pteris nervosa and their relations to arsenic accumulation

    Institute of Scientific and Technical Information of China (English)

    CHEN Tongbin; HUANG Zechun; HUANG Yuying; XIE Hua; LIAO Xiaoyong

    2003-01-01

    Synchrotron radiation X-ray fluorescencespectroscopy (SRXRF) was used to study the cellular distri-butions of arsenic and other elements in root, petiole, pinna of a newly discovered arsenic hyperaccumulator, Pteris nervosa. It was shown that there was a trend in P. nervosa totransport arsenic from cortex tissue to vascular tissue in root, and keep arsenic in vascular during transportation in petiole, and transport arsenic from vascular tissue to adaxial cortex tissues in midrib of pinnae. More arsenic was accumulated in mesophyll than in epidermis in pinnae. The distributions of some elements, such as K, Ca, Mn, Fe, Cu, Zn, in petiole, midrib and pinna were similar to that of arsenic, indicating that those cations might cooperate with arsenic in those transportation processes; whereas the distributions of Cl and Br in pinna were the reverse of that of arsenic, indicating that those anions might compete with arsenic in pinna of P. nervosa.

  16. Human pulpal response to mineral trioxide aggregate (MTA): a histologic study.

    Science.gov (United States)

    Chacko, Varghese; Kurikose, Sobha

    2006-01-01

    The purpose of this study was to study the histologic changes in the dental pulp following pulpotomy with Mineral Trioxide Aggregate (MTA) and Calcium hydroxide. Pulpotomies were performed on premolar teeth that were to be extracted for orthodontic reasons. The radicular pulp was capped with either MTA or Calcium hydroxide and restored with IRM. The teeth were extracted at 4 and 8 week intervals, fixed in 10% formalin and then kept in 5% nitric acid for 28 days for demineralization. Longitudinal sections were then prepared and viewed under light microscope. The pulps capped with MTA (at the end of 4 weeks and 8 weeks) showed dentin bridge formation which was more homogenous and continuous with the original dentin when compared to the pulps capped with calcium hydroxide. The pulpal inflammation was also less in the MTA group as compared to the calcium hydroxide group at the end of 4 and 8 weeks.

  17. Mineral trioxide aggregate as pulp capping agent for primary teeth pulpotomy: 2 year follow up study.

    Science.gov (United States)

    Subramaniam, Priya; Konde, Sapna; Mathew, Somy; Sugnani, Sony

    2009-01-01

    The aim of the present study was to clinically and radiographically evaluate Mineral Trioxide Aggregate (MTA) as an agent for pulpotomy in primary teeth and to compare it with that of formocresol (FC) pulpotomy. Nineteen children between the ages of 6 to 8 years with 40 carious primary molars were treated with pulpotomy using either FC or MTA. All the molars were evaluated clinically and radiographically at regular intervals over a twenty four month period. The observations were tabulated and statistically analyzed. Eighty five percent success was observed with FC pulpotomy whereas MTA showed 95% success. MTA showed a higher clinical and radiographic success rate than FC. MTA may be a favorable material for pulpotomy in primary teeth whose pulps have been compromised by a carious or mechanical pulp exposure.

  18. Nonsurgical Endodontic Retreatment of Advanced Inflammatory External Root Resorption Using Mineral Trioxide Aggregate Obturation

    Directory of Open Access Journals (Sweden)

    Shivani Utneja

    2012-01-01

    Full Text Available Inflammatory external root resorption is one of the major complications after traumatic dental injury. In this case report, we describe treatment of a maxillary central incisor affected by severe, perforating external root resorption. An 18-year-old patient presented with a previously traumatized, root-filled maxillary central incisor associated with pain and sinus tract. Radiographic examination revealed periradicular lesion involving pathologic resorption of the apical region of the root and lateral root surface both mesially and distally. After removal of the root canal filling, the tooth was disinfected with intracanal triple antibiotic paste for 2 weeks. The antibiotic dressing was then removed, and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 18 months, significant osseous healing of the periradicular region and lateral periodontium had occurred with arrest of external root resorption, and no clinical symptoms were apparent.

  19. Treatment of severe inflammatory root resorption in a young permanent incisor with mineral trioxide aggregate.

    Science.gov (United States)

    Guzeler, Irem; Uysal, Serdar; Cehreli, Zafer C

    2011-01-01

    Inflammatory root resorption is a pathologic condition caused by several etiologic factors including traumatic dental injury. In this case report, we describe treatment of a maxillary lateral incisor affected by severe, perforating inflammatory root resorption. An 11-year-old patient presented with a previously traumatized, root-filled maxillary lateral incisor associated with pain, mobility and a sinus tract. Radiographic examination revealed a large periradicular lesion involving pathologic resorption of the apical region of the root. After removal of the root canal filling, the tooth was treated with intracanal calcium hydroxide for 2 weeks. The calcium hydroxide dressing was then removed and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 1 year, advanced osseous healing of the periradicular region had occurred and no clinical symptoms were apparent.

  20. Joint effects of microwave and chromium trioxide on root tip cells of Vicia faba

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The mutagenic effects of microwave and chromium trioxide (CrO3) on Viciafaba root tip were studied. Micronucleus assay and chromosomal aberration assay were used to determine the mitotic index, the micronucleus frequency and chromosomal aberration frequency of Vicia faba root tip cells induced by microwave and CrO3. The results showed that the micronucleus frequency decreased, and that the mitotic index and chromosomal aberration frequency showed linear dose responses to CrO3, in treatment of microwave for 5 s. In microwave of 25 s, the mitotic index decreased, the micronucleus frequency and chromosomal aberration frequency increased with increase of CrO3 concentration. We concluded that microwave and CrO3 had antagonistic effect on the mitotic index of Vicia faba root tip cells, but had synergetic effect on micronucleus frequency and chromosomal aberration frequency of Vicia faba root tip cells.

  1. Mutagenic effects of chromium trioxide on root tip cells of Vicia faba

    Institute of Scientific and Technical Information of China (English)

    钱晓薇

    2004-01-01

    In this study on the mutagenic effects of different concentrations of chromium trioxide (CrO3) on Vicia faba root tip, micronucleus assay and chromosome aberration assay were used to determine the mitotic indexes, micronucleus rate and chromosome aberration rate of Viciafaba root tip cells. The results showed that the effects of CrO3 concentration on the mitotic indexes were complicated. CrO3 increases the micronucleus rate of Vicia faba root tip cells. It was found that within certain range of CrO3 concentration the micronucleus rate increased systematically with increased concentration of CrO3, but that the micronucleus rate decreased at higher level of CrO3 and that CrO3 also caused various types of chromosome aberration at a rate which increased systematically with increased concentration of CrO3. We concluded that CrO3 has significant mutagenic effect on Viciafaba root tip cells.

  2. Mutagenic effects of chromium trioxide on root tip cells of Vicia faba

    Institute of Scientific and Technical Information of China (English)

    钱晓徽

    2004-01-01

    In this study on the mutagenic effects of different concentrations of chromium trioxide (CrO3) on Vicia faba root tip, micronucleus assay and chromosome aberration assay were used to determine the mitotic indexes, micronucleus rate and chromosome aberration rate of Vicia faba root tip cells. The results showed that the effects of CrO3 concentration on the mitotic indexes were complicated. CrO3 increases the micronucleus rate of Vicia faba root tip cells. It was found that within certain range of CrO3 concentration the micronucleus rate increased systematically with increased concentration of CrO3, but that the micronucleus rate decreased at higher level of CrO3 and that CrO3 also caused various types of chromosome aberration at a rate which increased systematically with increased concentration of CrO3. We concluded that CrO3 has significant mutagenic effect on Vicia faba root tip cells.

  3. Mineral trioxide aggregate pulpotomy: An ideal treatment option for management of talon cusp

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2012-01-01

    Full Text Available To use mineral trioxide aggregate (MTA in prophylactic management of talon cusp. Talon cusp is an endodontic oddity that possesses a treatment challenge to the clinician, especially when it causes esthetic and functional problems. Management ranges from periodic gradual reduction to radical removal followed by vital pulp/endodontic therapy. MTA has replaced calcium hydroxide as pulp capping material because of its superior properties. A 12-year-old boy reported with a complaint of irregular teeth. Clinical and radiographic examination revealed talon cusp on maxillary left central incisor. Radical removal of talon cusp and MTA pulpotomy was performed. The 4-year follow-up showed the positive pulp vitality test without any radiographic changes, emphasizing the use of MTA pulpotomy in successful management of talon cusp.

  4. Histology of Irreversible pulpitis premolars treated with mineral trioxide aggregate pulpotomy.

    Science.gov (United States)

    Chueh, Ling-Huey; Chiang, Chun-Pun

    2010-01-01

    Studies show that human permanent teeth with carious pulpal exposures can result in a high clinical success rate when treated with pulpotomy and direct pulp capping with mineral trioxide aggregate (MTA pulpotomy). In this case report, a 19-year-old female patient with a second premolar with irreversible pulpitis and symptomatic apical periodontitis was treated with MTA pulpotomy. Follow-up electric pulp tests showed viability of the tooth at three and 10 months. Ten months after the initial treatment, the tooth was extracted for orthodontic reasons and processed for histological examination. Microscopically, the pulpal wound treated with MTA was free from inflammation and covered with a thin layer of reparative dentin. The authors conclude that, when caries and bacterial contamination can be removed from the dentin-pulp complex, the inflamed but vital pulp of a permanent tooth may have a chance to return to a healthy, functional status after MTA pulpotomy.

  5. Preparation of nanometer δ-and β-bismuth trioxide by vacuum vapor-phase oxidation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A stable δ- and β-bismuth trioxide was prepared at room temperature by vacuum vapor-phase oxidation. The average crystal size of products was 14.6 nm (by XRD), the d(0.5) value was in the range from 62 nm to 69 nm, and geometric standard deviation(GSD)was from 1.42 to 1.64. The results show that δ-Bi2O3 is formed when quenching rates is rapid and β-Bi2O3 is formed when it is slow. The size of grains increases with rising reaction temperature, flow rate of carrier gas, residual pressure of system and longer growing time of grains.

  6. AC conductivity and dielectric properties of bulk tungsten trioxide (WO{sub 3})

    Energy Technology Data Exchange (ETDEWEB)

    El-Nahass, M.M. [Department of Physics, Faculty of Education, Ain Shams University, Roxy 11757, Cairo (Egypt); Ali, H.A.M., E-mail: hend2061@yahoo.com [Department of Physics, Faculty of Education, Ain Shams University, Roxy 11757, Cairo (Egypt); Saadeldin, M.; Zaghllol, M. [Physics Department, Faculty of Science, Cairo University, Giza 12613 (Egypt)

    2012-11-15

    AC conductivity and dielectric properties of tungsten trioxide (WO{sub 3}) in a pellet form were studied in the frequency range from 42 Hz to 5 MHz with a variation of temperature in the range from 303 K to 463 K. AC conductivity, {sigma}{sub ac}({omega}) was found to be a function of {omega}{sup s} where {omega} is the angular frequency and s is the frequency exponent. The values of s were found to be less than unity and decrease with increasing temperature, which supports the correlated barrier hopping mechanism (CBH) as the dominant mechanism for the conduction in WO{sub 3}. The dielectric constant ({epsilon} Prime ) and dielectric loss ({epsilon} Double-Prime ) were measured. The Cole-Cole diagram determined complex impedance for different temperatures.

  7. The effect of using propylene glycol as a vehicle on the microhardness of mineral trioxide aggregate.

    Science.gov (United States)

    Salem Milani, Amin; Banifatemeh, Alireza; Rahimi, Saeed; Jafarabadi, Mohammad Asghari

    2015-01-01

    While it has been proven that the handling properties of mineral trioxide aggregate (MTA) are improved upon mixing it with propylene glycol (PG), this study sought to evaluate how PG affects the microhardness of MTA in terms of setting quality. MTA was mixed with different proportions of distilled water (DW) and PG to prepare 5 groups (n = 30). The DW/PG percent proportions used in Groups 1-5 were 100/0, 80/20, 50/50, 20/80, and 0/100, respectively. The mixed MTA was condensed into acrylic molds. Half of the samples of each group were evaluated on Day 4, the other half on Day 28. The results indicated that PG reduces the microhardness of MTA, thus adversely affecting its setting process. Group 2 (80% DW/20% PG) best improved the handling of MTA without a significant reduction in setting quality.

  8. Fracture resistance and histological findings of immature teeth treated with mineral trioxide aggregate

    DEFF Research Database (Denmark)

    Hatibovic-Kofman, S.; Raimundo, L.; Zheng, L.

    2008-01-01

    The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time. Immature mandibular incisors from sheep were extracted and the pulps were extirpated using an apical approach...... with a barbed broach, and the teeth were divided into three experimental groups. Group 1: untreated teeth. Group 2: the root canals were filled with calcium hydroxide paste. Group 3: the root canals were filled with MTA. All specimens were kept in saline with 1% antibiotics at 4 degrees C for certain periods...... for a histological study, examining matrix metalloproteinases (MMP2 and MMP14) and tissue inhibitor of metalloproteinase (TIMP). The results showed the mean fracture strengths decreased over time for all the three groups. Although the untreated teeth showed the highest value (45.5 MPa) at 2 weeks, the fracture...

  9. Management of External Invasive Cervical Resorption Tooth with Mineral Trioxide Aggregate: A Case Report

    Directory of Open Access Journals (Sweden)

    Anuja Ikhar

    2013-01-01

    Full Text Available Invasive cervical resorption is entirely uncommon entities and the etiology is poorly understood. A 19 year old patient presented with fractured upper left central incisor and sinus tract opening on the distobuccal aspect in cervical region. Radiographic examination shows irregular radiolucency over the coronal one-third and it extended externally towards the external invasive resorption. After sectional obturation, the defect was accessed surgically. The resorption area was chemomechanically debrided using irrigant solution. Fibre post placement using flowable composite resin and Mineral Trioxide Aggregate (MTA was used to fill the resorptive defect, and the coronal access was temporarily sealed. Composite restoration was subsequently replaced with ceramic crown after 4 years. Radiographs at 1 and 4 years showed adequate repair of the resorption and endodontic success. Clinically and radiographically the tooth was asymptomatic, and no periodontal pocket was found after a 4-year followup.

  10. Dissolution of a mineral trioxide aggregate sealer in endodontic solvents compared to conventional sealers

    Directory of Open Access Journals (Sweden)

    Hanan ALZRAIKAT

    2016-01-01

    Full Text Available Abstract The aim of this study is to evaluate the solubility of a Mineral Trioxide Aggregate sealer (MTA-Fillapex compared with five other sealers, calcium hydroxide (Sealapex, resin (Realseal, zinc oxide-eugenol (Tubli-Seal, and two epoxy resins (AH-26 and AH-Plus, in chloroform and eucalyptoil in static and ultrasonic environments. Samples of each sealer were prepared (n = 180 and then divided into 12 groups that were immersed in solvents for 5 and 10 min in static and ultrasonic environments. The mean weight loss was determined, and the values were compared using Student’s t-test, One-way ANOVA, and Tukey’s HSD post-hoc test (p 0.05. In conclusion, MTA-Fillapex was not sufficiently dissolved in either solvent. Ultrasonic activation had limited effectiveness on MTA-Fillapex dissolution, whereas it significantly increased the efficiency of solvents in dissolving a number of endodontic sealers.

  11. Treatment of inflammatory root resorption using mineral trioxide aggregate: A case report

    Directory of Open Access Journals (Sweden)

    Roohollah Sharifi

    2014-01-01

    Full Text Available Introduction: This report presents a case to show inflammatory root resorption can be successfully treated by using mineral trioxide aggregate (MTA. Case Report: A central maxillary incisor of an eight-year-old boy was avulsed associated with crown fracture secondary to a fall. The tooth was stored in ice. Early attempts at pulpal revascularization of the replanted tooth proved unsuccessful. To stop inflammatory root resorption, long-term calcium hydroxide therapy was employed. Despite the use of calcium hydroxide, resorption continued. Subsequent to the failure of that treatment, MTA was used as a root canal filling material. At 20-month follow-up, the tooth was asymptomatic and had clinical signs of ankylosis but external inflammatory root resorption had stopped. Discussion: MTA may be considered as an alternative option for the treatment of continuous external inflammatory root resorption.

  12. Management of immature teeth with apical infections using mineral trioxide aggregate

    Directory of Open Access Journals (Sweden)

    Sivakumar Nuvvula

    2010-01-01

    Full Text Available Traumatic injuries to the young permanent teeth lead to devitalization of the pulp with concomitant arrest in further development of the immature root of the involved tooth. Hermetic seal of the root canal system during obturation is not possible in such cases, due to the lack of an apical constriction. The traditional management technique in such cases has been apexification involving induction of a calcific barrier at the apex using calcium hydroxide, which in turn facilitates obturation of the root canal. However this becomes complicated when there is persistent infection leading to periapical changes. This case report describes the use of mineral trioxide aggregate (MTA for management of a periapically compromised immature tooth.

  13. Geostatistical modelling of arsenic in drinking water wells and related toenail arsenic concentrations across Nova Scotia, Canada.

    Science.gov (United States)

    Dummer, T J B; Yu, Z M; Nauta, L; Murimboh, J D; Parker, L

    2015-02-01

    Arsenic is a naturally occurring class 1 human carcinogen that is widespread in private drinking water wells throughout the province of Nova Scotia in Canada. In this paper we explore the spatial variation in toenail arsenic concentrations (arsenic body burden) in Nova Scotia. We describe the regional distribution of arsenic concentrations in private well water supplies in the province, and evaluate the geological and environmental features associated with higher levels of arsenic in well water. We develop geostatistical process models to predict high toenail arsenic concentrations and high well water arsenic concentrations, which have utility for studies where no direct measurements of arsenic body burden or arsenic exposure are available. 892 men and women who participated in the Atlantic Partnership for Tomorrow's Health Project provided both drinking water and toenail clipping samples. Information on socio-demographic, lifestyle and health factors was obtained with a set of standardized questionnaires. Anthropometric indices and arsenic concentrations in drinking water and toenails were measured. In addition, data on arsenic concentrations in 10,498 private wells were provided by the Nova Scotia Department of Environment. We utilised stepwise multivariable logistic regression modelling to develop separate statistical models to: a) predict high toenail arsenic concentrations (defined as toenail arsenic levels ≥0.12 μg g(-1)) and b) predict high well water arsenic concentrations (defined as well water arsenic levels ≥5.0 μg L(-1)). We found that the geological and environmental information that predicted well water arsenic concentrations can also be used to accurately predict toenail arsenic concentrations. We conclude that geological and environmental factors contributing to arsenic contamination in well water are the major contributing influences on arsenic body burden among Nova Scotia residents. Further studies are warranted to assess appropriate

  14. Arsenic Induction of Metallothionein and Metallothionein Induction Against Arsenic Cytotoxicity.

    Science.gov (United States)

    Rahman, Mohammad Tariqur; De Ley, Marc

    Human exposure to arsenic (As) can lead to oxidative stress that can become evident in organs such as the skin, liver, kidneys and lungs. Several intracellular antioxidant defense mechanisms including glutathione (GSH) and metallothionein (MT) have been shown to minimize As cytotoxicity. The current review summarizes the involvement of MT as an intracellular defense mechanism against As cytotoxicity, mostly in blood. Zinc (Zn) and selenium (Se) supplements are also proposed as a possible remediation of As cytotoxicity. In vivo and in vitro studies on As toxicity were reviewed to summarize cytotoxic mechanisms of As. Intracellular antioxidant defense mechanisms of MT are linked in relation to As cytotoxicity. Arsenic uses a different route, compared to major metal MT inducers such as Zn, to enter/exit blood cells. A number of in vivo and in vitro studies showed that upregulated MT biosynthesis in blood components are related to toxic levels of As. Despite the cysteine residues in MT that aid to bind As, MT is not the preferred binding protein for As. Nonetheless, intracellular oxidative stress due to As toxicity can be minimized, if not eliminated, by MT. Thus MT induction by essential metals such as Zn and Se supplementation could be beneficial to fight against As toxicity.

  15. Social implications of arsenic poisoning in Bangladesh.

    Science.gov (United States)

    Hassan, M Manzurul; Atkins, Peter J; Dunn, Christine E

    2005-11-01

    Besides its toxicity, groundwater arsenic contamination creates widespread social problems for its victims and their families in Bangladesh. There is, for instance, a tendency to ostracise arsenic-affected people, arsenicosis being thought of as a contagious disease. Within the community, arsenic-affected people are barred from social activities and often face rejection, even by their immediate family members. Women with visible arsenicosis symptoms are unable to get married and some affected housewives are divorced by their husbands. Children with symptoms are not sent to school in an effort to hide the problem. This paper employs mainly qualitative methods to interpret people's understandings about the toxic impact of groundwater arsenic poisoning on their social lives. Arsenic-affected patients in southwest Bangladesh were asked to determine their 'own priorities' in measuring arsenic toxicity on their social activities and to explore their perceptions about their own survival strategies. We found that patients' experiences reveal severe negative social impacts, and a sharp difference of perceptions about arsenic and social issues between arsenicosis patients and unaffected people.

  16. [Competitive Microbial Oxidation and Reduction of Arsenic].

    Science.gov (United States)

    Yang, Ting-ting; Bai, Yao-hui; Liang, Jin-song; Huo, Yang; Wang, Ming-xing; Yuan, Lin-ijang

    2016-02-15

    Filters are widely applied in drinking water treatment plants. Our previous study, which explored the asenic redox in a filter of drinking water plant treating underground water, found that As3+ could be oxidized to As5+ by biogenic manganese oxides, while As5+ could be reduced to As3+ by some microbial arsenic reductases in the biofilter system. This microbial competition could influence the system stability and treatment efficiency. To explore its mechanism, this study selected a manganese-oxidizing bacterial strain (Pseudomonas sp. QJX-1) and a arsenic-reducing strain (Brevibacterium sp. LSJ-9) to investigate their competitive relationship in nutrient acquisition and arsenic redox in the presence of Mn2+, As3+ or As5+ The results revealed that the concentration and valence of Mn and As varied with different reaction time; biological manganese oxides dominated the arsenic redox by rapidly oxidizing the As3+ in the existing system and the As3+ generated by arsenic reductase into As. PCR and RT-PCR results indicated that the arsenic reductase (arsC) was inhibited by the manganese oxidase (cumA). The expression of 16S rRNA in QJX-1 was two orders of magnitude higher than that in LSJ-9, which implied QJX-1 was dominant in the bacterial growth. Our data revealed that hydraulic retention time was critical to the valence of arsenic in the effluent of filter in drinking water treatment plant.

  17. Identification of an Arsenic Resistance and Arsenic-Sensing System in Campylobacter jejuni▿ †

    OpenAIRE

    Wang, Liping; Jeon, Byeonghwa; Sahin, Orhan; Zhang, Qijing

    2009-01-01

    Arsenic is commonly present in the natural environment and is also used as a feed additive for animal production. Poultry is a major reservoir for Campylobacter jejuni, a major food-borne human pathogen causing gastroenteritis. It has been shown that Campylobacter isolates from poultry are highly resistant to arsenic compounds, but the molecular mechanisms responsible for the resistance have not been determined, and it is unclear if the acquired arsenic resistance affects the susceptibility o...

  18. Arsenic adsorption of lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil

    Directory of Open Access Journals (Sweden)

    Wuthiphun, L.

    2007-05-01

    Full Text Available Arsenic adsorption efficiency of soil covering materials (lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil obtained from Ronpiboon District, Nakhon Sri Thammarat Province tosolve arsenic air pollution problem was investigated using batch experiments. The four types of the aforementioned soil covering materials were examined to determine their arsenic adsorption efficiency, equilibriumtime as well as adsorption isotherms.The results revealed that among soil covering materials mixed with arsenic-contaminated soil at 10% w/w, the efficiency of arsenic adsorption of fly ash, lateritic soil, lime and limestone powder were 84, 60,38 and 1% respectively. The equilibrium time for lateritic soil at pH 4 was achieved within 4 hrs, whereas pH 7 and 12, the equilibrium time was 6 hrs. For fly ash, 2 hrs were required to reach the equilibrium at pH 12, while the equilibrium time was attained within 6 hrs at pH 4 and 7. Furthermore, lateritic soil possessedhigh arsenic adsorption efficiency at pH 7 and 4 and best fit with the Langmuir isotherm. The fly ash showing high arsenic adsorption efficiency at pH 12 and 7 fit the Freundlich isotherm at pH 12 and Langmuirisotherm at pH 7.This indicated that lateritic soil was suitable for arsenic adsorption at low pH, whilst at high pH,arsenic was well adsorbed by fly ash. The Freundlich and Langmuir isotherm could be used to determine quantities of soil covering materials for arsenic adsorption to prevent arsenic air pollution from arseniccontaminated soils.

  19. Arsenic in North Carolina: public health implications.

    Science.gov (United States)

    Sanders, Alison P; Messier, Kyle P; Shehee, Mina; Rudo, Kenneth; Serre, Marc L; Fry, Rebecca C

    2012-01-01

    Arsenic is a known human carcinogen and relevant environmental contaminant in drinking water systems. We set out to comprehensively examine statewide arsenic trends and identify areas of public health concern. Specifically, arsenic trends in North Carolina private wells were evaluated over an eleven-year period using the North Carolina Department of Health and Human Services database for private domestic well waters. We geocoded over 63,000 domestic well measurements by applying a novel geocoding algorithm and error validation scheme. Arsenic measurements and geographical coordinates for database entries were mapped using Geographic Information System techniques. Furthermore, we employed a Bayesian Maximum Entropy (BME) geostatistical framework, which accounts for geocoding error to better estimate arsenic values across the state and identify trends for unmonitored locations. Of the approximately 63,000 monitored wells, 7712 showed detectable arsenic concentrations that ranged between 1 and 806μg/L. Additionally, 1436 well samples exceeded the EPA drinking water standard. We reveal counties of concern and demonstrate a historical pattern of elevated arsenic in some counties, particularly those located along the Carolina terrane (Carolina slate belt). We analyzed these data in the context of populations using private well water and identify counties for targeted monitoring, such as Stanly and Union Counties. By spatiotemporally mapping these data, our BME estimate revealed arsenic trends at unmonitored locations within counties and better predicted well concentrations when compared to the classical kriging method. This study reveals relevant information on the location of arsenic-contaminated private domestic wells in North Carolina and indicates potential areas at increased risk for adverse health outcomes.

  20. Determination of total arsenic, inorganic and organic arsenic species in wine.

    Science.gov (United States)

    Herce-Pagliai, C; Moreno, I; González, G; Repetto, M; Cameán, A M

    2002-06-01

    Forty-five wine samples from the south of Spain of different alcoholic strength were analysed for total arsenic and its inorganic [As(III), As(V)] and organic (monomethylarsonic acid [MMAA], dimethylarsinic acid [DMAA]) species. The As levels of the wine samples ranged from 2.1 to 14.6 microg l(-1). The possible effect of the alcoholic fermentation process on the levels of the total arsenic and arsenical species was studied. The average total arsenic levels for the different samples were very similar, without significant differences between all types of wines. In table wines and sherry, the percentages of total inorganic arsenic were 18.6 and 15.6%, with DMAA or MMAA being the predominant species, respectively. In most samples, DMAA was the most abundant species, but the total inorganic aresenic fraction was considerable, representing 25.4% of the total concentration of the element. The estimated daily intakes of total arsenic and total inorganic arsenic for average Spanish consumers were 0.78 and 0.15 microg/person day(-1), respectively. The results suggest that the consumption of these types of wines makes no significant contribution to the total and inorganic arsenic intake for normal drinkers. However, wine consumption contributes a higher arsenic intake than through consumption of beers and sherry brandies.

  1. Electrochemical arsenic remediation for rural Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Addy, Susan Amrose [Univ. of California, Berkeley, CA (United States)

    2008-01-01

    Arsenic in drinking water is a major public health problem threatening the lives of over 140 million people worldwide. In Bangladesh alone, up to 57 million people drink arsenic-laden water from shallow wells. ElectroChemical Arsenic Remediation(ECAR) overcomes many of the obstacles that plague current technologies and can be used affordably and on a small-scale, allowing for rapid dissemination into Bangladesh to address this arsenic crisis. In this work, ECAR was shown to effectively reduce 550 - 580 μg=L arsenic (including both As[III]and As[V]in a 1:1 ratio) to below the WHO recommended maximum limit of 10 μg=L in synthetic Bangladesh groundwater containing relevant concentrations of competitive ions such as phosphate, silicate, and bicarbonate. Arsenic removal capacity was found to be approximately constant within certain ranges of current density, but was found to change substantially between ranges. In order of decreasing arsenic removal capacity, the pattern was: 0.02 mA=cm2> 0.07 mA=cm2> 0.30 - 1.1 mA=cm2> 5.0 - 100 mA=cm2. Current processing time was found to effect arsenic removal capacity independent of either charge density or current density. Electrode polarization studies showed no passivation of the electrode in the tested range (up to current density 10 mA=cm2) and ruled out oxygen evolution as the cause of decreasing removal capacity with current density. Simple settling and decantation required approximately 3 days to achieve arsenic removal comparable to filtration with a 0.1 mu m membrane. X-ray Absorption Spectroscopy (XAS) showed that (1) there is no significant difference in the arsenic removal mechanism of ECAR during operation at different current densities and (2) the arsenic removal mechanism in ECAR is consistent with arsenate adsorption onto a homogenous Fe(III)oxyhydroxide similar in structure to 2-line ferrihydrite. ECAR effectively reduced high arsenic concentrations (100

  2. Arsenic in rice: A cause for concern

    DEFF Research Database (Denmark)

    Hojsak, Iva; Braegger, Christian; Bronsky, Jiri

    2015-01-01

    Inorganic arsenic intake is likely to affect long-term health. High concentrations are found in some rice-based foods and drinks widely used in infants and young children. In order to reduce exposure we recommend avoidance of rice drinks for infants and young children. For all rice products, strict...... regulation should be enforced regarding arsenic content. Moreover, infants and young children should consume a balanced diet including a variety of grains as carbohydrate sources. While rice protein based infant formulas are an option for infants with cows' milk protein allergy, the inorganic arsenic content...

  3. Current research of the relationship between arsenic and eye disease%砷与眼科疾病关系的研究现状

    Institute of Scientific and Technical Information of China (English)

    李建国

    2012-01-01

    Traditionally,arsenic is thought to be a strong toxicant,especially arsenic trioxide (As2O3 ).As2O3 leads to the damage of ocular surface,such as cornea,conjunctiva etc.,and the evidence of its damage to retinal function also has been found.However,arsenic is a double-edged sword,because it possesses well- remedial effect on some eye diseases,including proliferative diabetic retinopathy,lens posterior capsular opaciffcation,keratopathy,meIanoma and bleb scarring.At present,there is still few research literature was seen about the active mechanism of arsenic agents on eye damage or therapeutic effect.Some relative studies are still in an experimental stage.This offers us the new research direction in clinical treatment of eye diseases.It is believed that arsenic will play an incalculable role on experiment and clinical treatment of eye diseases as further development and research of technology.The relationship between arsenic and eye disease is summed by consulting internal and external literature.%传统的认识认为砷是一种剧毒物质,尤其是As2O3,不仅能导致眼表的损害,还可影响视网膜的功能.随着研究的深入,目前认为砷是一把双刃剑,其对眼部疾病亦可发挥治疗作用,如砷类制剂对视网膜病变、后发性白内障、角膜病变、黑色素瘤、滤过泡瘢痕化等的治疗效果较好.总的来说,砷对眼部的损伤作用以及对眼病治疗作用的机制研究均较少,多数研究仍处于实验阶段,但这些研究为一些眼科疾病的临床治疗提供了新的研究方向,砷与眼部疾病的实验与临床研究结果正在引起更多的关注.就砷对眼部疾病的损伤和治疗作用进行综述.

  4. Mathematical model insights into arsenic detoxification

    Directory of Open Access Journals (Sweden)

    Nijhout H Frederik

    2011-08-01

    Full Text Available Abstract Background Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs, which then undergoes hepatic methylation to methylarsonic acid (MMAs and a second methylation to dimethylarsinic acid (DMAs. Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation. Methods We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects. Results We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic

  5. Flexible neutron shielding composite material of EPDM rubber with boron trioxide: Mechanical, thermal investigations and neutron shielding tests

    Science.gov (United States)

    Özdemir, T.; Güngör, A.; Reyhancan, İ. A.

    2017-02-01

    In this study, EPDM and boron trioxide composite was produced and mechanical, thermal and neutron shielding tests were performed. EPDM rubber (Ethylene Propylene Diene Monomer) having a considerably high hydrogen content is an effective neutron shielding material. On the other hand, the materials containing boron components have effective thermal neutron absorption crossection. The composite of EPDM and boron trioxide would be an effective solution for both respects of flexibility and effectiveness for developing a neutron shielding material. Flexible nature of EPDM would be a great asset for the shielding purpose in case of intervention action to a radiation accident. The theoretical calculations and experimental neutron absorption tests have shown that the results were in parallel and an effective neutron shielding has been achieved with the use of the developed composite material.

  6. An ex-vivo comparative study of root-end marginal adaptation using grey mineral trioxide aggregate, white mineral trioxide aggregate, and Portland cement under scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Akash Kumar Baranwal

    2015-01-01

    Full Text Available Context: Where nonsurgical endodontic intervention is not possible, or it will not solve the problem, surgical endodontic treatment must be considered. A major cause of surgical endodontic failures is an inadequate apical seal, so the use of the suitable substance as root-end filling material that prevents egress of potential contaminants into periapical tissue is very critical. Aims: The aim of the present ex-vivo study was to compare and evaluate the three root-end filling materials of mineral trioxide aggregate (MTA family (white MTA [WMTA], grey MTA [GMTA] and Portland cement [PC] for their marginal adaptation at the root-end dentinal wall using scanning electron microscopy (SEM. Materials and Methods: Sixty human single-rooted teeth were decoronated, instrumented, and obturated with Gutta-percha. After the root-end resection and apical cavity preparation, the teeth were randomly divided into three-experimental groups (each containing 20 teeth and each group was filled with their respective experimental materials. After longitudinal sectioning of root, SEM examination was done to determine the overall gap between retrograde materials and cavity walls in terms of length and width of the gap (maximum at the interface. Descriptive statistical analysis was performed to calculate the means with corresponding standard errors, median and ranges along with an analysis of variance and Tukey′s test. Results: The least overall gap was observed in GMTA followed by PC and WMTA. While after statistically analyzing the various data obtained from different groups, there was no significant difference among these three groups in terms of marginal adaptation. Conclusion: GMTA showed the best overall adaptation to root dentinal wall compared to PC and WMTA. Being biocompatible and cheaper, the PC may be an alternative but not a substitute for MTA.

  7. An ex-vivo comparative study of root-end marginal adaptation using grey mineral trioxide aggregate, white mineral trioxide aggregate, and Portland cement under scanning electron microscopy

    Science.gov (United States)

    Baranwal, Akash Kumar; Paul, Mohan L.; Mazumdar, Dibyendu; Adhikari, Haridas Das; Vyavahare, Nishant K.; Jhajharia, Kapil

    2015-01-01

    Context: Where nonsurgical endodontic intervention is not possible, or it will not solve the problem, surgical endodontic treatment must be considered. A major cause of surgical endodontic failures is an inadequate apical seal, so the use of the suitable substance as root-end filling material that prevents egress of potential contaminants into periapical tissue is very critical. Aims: The aim of the present ex-vivo study was to compare and evaluate the three root-end filling materials of mineral trioxide aggregate (MTA) family (white MTA [WMTA], grey MTA [GMTA] and Portland cement [PC]) for their marginal adaptation at the root-end dentinal wall using scanning electron microscopy (SEM). Materials and Methods: Sixty human single-rooted teeth were decoronated, instrumented, and obturated with Gutta-percha. After the root-end resection and apical cavity preparation, the teeth were randomly divided into three-experimental groups (each containing 20 teeth) and each group was filled with their respective experimental materials. After longitudinal sectioning of root, SEM examination was done to determine the overall gap between retrograde materials and cavity walls in terms of length and width of the gap (maximum) at the interface. Descriptive statistical analysis was performed to calculate the means with corresponding standard errors, median and ranges along with an analysis of variance and Tukey's test. Results: The least overall gap was observed in GMTA followed by PC and WMTA. While after statistically analyzing the various data obtained from different groups, there was no significant difference among these three groups in terms of marginal adaptation. Conclusion: GMTA showed the best overall adaptation to root dentinal wall compared to PC and WMTA. Being biocompatible and cheaper, the PC may be an alternative but not a substitute for MTA. PMID:26430305

  8. Evaluation and comparison of white mineral trioxide aggregate and formocresol medicaments in primary tooth pulpotomy: Clinical and radiographic study

    OpenAIRE

    Cheranjeevi Jayam; Malay Mitra; Jiban Mishra; Bhaswar Bhattacharya; Biswanath Jana

    2014-01-01

    Aim: The primary aim of the following study is to evaluate and secondary aim is to compare clinically and radiographically the success of using white mineral trioxide aggregate (MTA) versus formocresol (FC) medicament for primary tooth pulpotomy. Materials and Methods: A total of 100 teeth were selected for pulpotomy; of which 50 teeth underwent FC pulpotomy and 50 teeth underwent pulpotomy with white MTA. Out of 100 treated teeth, 82 teeth (42 FC and 40 MTA teeth) were available at the end o...

  9. Treatment of maxillary central incisor with external root resorption using mineral trioxide aggregate: 18 months follow-up

    OpenAIRE

    2013-01-01

    External cervical resorption is the loss of dental hard tissue as a result of odontoclastic action; it usually begins on the cervical region of the root surface of the teeth. This case report demonstrates an external cervical resorption in a maxillary central incisor of a 24-year-old male patient. After surgical intervention and root canal treatment, the resorption was subsequently sealed with mineral trioxide aggregate. The 18 months follow-up demonstrates no pathological changes on clinical...

  10. Repair of incomplete horizontal mid-root fracture of maxillary central incisor with mineral trioxide aggregate: A follow up report

    Directory of Open Access Journals (Sweden)

    Ashwinkumar Krushnarao Chute

    2014-01-01

    Full Text Available Incomplete horizontal fractures occur in teeth with developing root as it cannot withstand traumatic force during injury. Diagnosis and management of such cases are difficult. Cone Beam Computed Tomography (CBCT served as efficient diagnostic tool and follow up measure and the use of Mineral Trioxide Aggregate in treatment had shown a better prognostic importance. In present case, treatment outcome of one year is reported in incompletely fractured mid-root of central incisor and the clinical approach is discussed.

  11. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada Region.

    Directory of Open Access Journals (Sweden)

    Adam James Houben

    Full Text Available Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3 dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As concentrations are well above guidelines for drinking water (10 μg/L and protection for aquatic life (5 μg/L, ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.

  12. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada) Region.

    Science.gov (United States)

    Houben, Adam James; D'Onofrio, Rebecca; Kokelj, Steven V; Blais, Jules M

    2016-01-01

    Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.

  13. Ana insect model for assessing arsenic toxicity: Arsenic elevated glutathione content in the musca domestica and trichoplusia ni

    Energy Technology Data Exchange (ETDEWEB)

    Zaman, K.; Pardini, R.S. [Univ. of Nevada, Reno, NV (United States)

    1995-12-01

    Throughout history, arsenic has acquired an unparalled reputation as a poison. Arsenic was used as a poison as early as 2000 B.C. The toxicity of arsenic (As) extends to mammals, fish, insects, plants and fungi. According to epidemiological evidence, inorganic arsenic compounds have been strongly suggested as human carcinogens. Human exposure to arsenic through various means is correlated with an increased incidence of skin, lung, and possibly liver cancers. Inorganic trivalent arsenic is systematically more poisonous than the pentavalent form and it is possible that pentavalent arsenic is reduced to the trivalent form before exerting any toxic effects. This study focuses on the potential to use two insect species, the housefly, Musca domestica and the cabbage looper moth, Trichoplusia ni, and a model for the study of arsenic toxicity. After 48 hours of exposure to Arsenic, a significant induction of Glutathione level and subsequent decrease in the level of GSSG in both species were observed. 21 refs., 2 figs., 1 tab.

  14. [Effects of organic fertilization on arsenic absorption of pakchoi (Brassica chinensis) on arsenic-contaminated red soil].

    Science.gov (United States)

    Li, Lian-Fang; Geng, Zhi-Xi; Zeng, Xi-Bai; Bai, Ling-Yu; Su, Shi-Ming

    2011-01-01

    A pot experiment with arsenic-contaminated red soil was conducted to study the effects of applying pig dung and chicken manure on the growth and arsenic absorption of pakchoi (Brassica chinensis), and on soil available arsenic. Applying pig dung and chicken manure to the arsenic-contaminated red soil increased the biomass of pakchoi to some extent. Comparing with the control, applying pig dung increased the pakchoi biomass significantly (P Organic fertilization promoted the arsenic absorption of pakchoi, with the arsenic uptake after applying pig dung increased by 20.7%-53.9%. The application of pig dung and chicken manure to arsenic-contaminated red soil could somewhat increase the soil available arsenic content and the arsenic uptake by crops, and thus, increase the risks of agricultural product quality and environment.

  15. Arsenic poisoning of cattle and other domestic animals

    Energy Technology Data Exchange (ETDEWEB)

    Moxham, J.W.; Coup, M.R.

    1968-01-01

    One hundred and sixty-one incidents of arsenic poisoning in domestic animals were recorded at Ruakura Veterinary Diagnostic Station from 1955 to 1967. Cattle was the animal species most subject to arsenic poisoning. Clincal signs, post-mortem findings and sources of arsenic are given. Arsenic poisoning was more prevalent in younger cattle and during the warmer months of the year. With cattle most incidents were associated with carelessly discarded arsenical compounds, although most deaths occurred when these compounds were deliberately used. In other species, losses were generally caused by the deliberate use of arsenical preparations for dipping, drenching and weed spraying. 10 references, 2 tables.

  16. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  17. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

    Science.gov (United States)

    Stanton, Bruce A; Caldwell, Kathleen; Congdon, Clare Bates; Disney, Jane; Donahue, Maria; Ferguson, Elizabeth; Flemings, Elsie; Golden, Meredith; Guerinot, Mary Lou; Highman, Jay; James, Karen; Kim, Carol; Lantz, R Clark; Marvinney, Robert G; Mayer, Greg; Miller, David; Navas-Acien, Ana; Nordstrom, D Kirk; Postema, Sonia; Rardin, Laurie; Rosen, Barry; SenGupta, Arup; Shaw, Joseph; Stanton, Elizabeth; Susca, Paul

    2015-09-01

    This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 μg/L in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies.

  18. Arsenic exposure from drinking water, arsenic methylation capacity, and carotid intima-media thickness in Bangladesh.

    Science.gov (United States)

    Chen, Yu; Wu, Fen; Graziano, Joseph H; Parvez, Faruque; Liu, Mengling; Paul, Rina Rani; Shaheen, Ishrat; Sarwar, Golam; Ahmed, Alauddin; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T; Desvarieux, Moise; Ahsan, Habibul

    2013-08-01

    We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010-2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 µg/g creatinine) and well-water arsenic (102.0 µg/L) concentration was related to a 11.7-µm (95% confidence interval (CI): 1.8, 21.6) and 5.1-µm (95% CI: -0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 µm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes.

  19. Arsenic stress after the Proterozoic glaciations

    Science.gov (United States)

    Chi Fru, Ernest; Arvestål, Emma; Callac, Nolwenn; El Albani, Abderrazak; Kilias, Stephanos; Argyraki, Ariadne; Jakobsson, Martin

    2015-12-01

    Protection against arsenic damage in organisms positioned deep in the tree of life points to early evolutionary sensitization. Here, marine sedimentary records reveal a Proterozoic arsenic concentration patterned to glacial-interglacial ages. The low glacial and high interglacial sedimentary arsenic concentrations, suggest deteriorating habitable marine conditions may have coincided with atmospheric oxygen decline after ~2.1 billion years ago. A similar intensification of near continental margin sedimentary arsenic levels after the Cryogenian glaciations is also associated with amplified continental weathering. However, interpreted atmospheric oxygen increase at this time, suggests that the marine biosphere had widely adapted to the reorganization of global marine elemental cycles by glaciations. Such a glacially induced biogeochemical bridge would have produced physiologically robust communities that enabled increased oxygenation of the ocean-atmosphere system and the radiation of the complex Ediacaran-Cambrian life.

  20. Arsenic binding to Fucus vesiculosus metallothionein.

    Science.gov (United States)

    Merrifield, Maureen E; Ngu, Thanh; Stillman, Martin J

    2004-11-05

    The seaweed Fucus vesiculosus is a member of the brown algae family. Kille and co-workers [Biochem. J. 338 (1999) 553] reported that this species contains the gene for metallothionein. Metallothionein is a metalloprotein having low molecular weight, and high cysteine content, which binds a range of metals. F. vesiculosus bioaccumulates arsenic from the aquatic environment [Mar. Chem. 18 (1986) 321]. In this paper we describe arsenic binding to F. vesiculosus metallothionein, characterized by electrospray ionization mass spectrometry. Five arsenic-MT species were detected with increasing As to protein ratios. These results provide important information about the metal-chelation behaviour of this novel algal metallothionein which is a putative model for arsenic binding to F. vesiculosus in vivo.

  1. Arsenic stress after the Proterozoic glaciations.

    Science.gov (United States)

    Fru, Ernest Chi; Arvestål, Emma; Callac, Nolwenn; El Albani, Abderrazak; Kilias, Stephanos; Argyraki, Ariadne; Jakobsson, Martin

    2015-12-04

    Protection against arsenic damage in organisms positioned deep in the tree of life points to early evolutionary sensitization. Here, marine sedimentary records reveal a Proterozoic arsenic concentration patterned to glacial-interglacial ages. The low glacial and high interglacial sedimentary arsenic concentrations, suggest deteriorating habitable marine conditions may have coincided with atmospheric oxygen decline after ~2.1 billion years ago. A similar intensification of near continental margin sedimentary arsenic levels after the Cryogenian glaciations is also associated with amplified continental weathering. However, interpreted atmospheric oxygen increase at this time, suggests that the marine biosphere had widely adapted to the reorganization of global marine elemental cycles by glaciations. Such a glacially induced biogeochemical bridge would have produced physiologically robust communities that enabled increased oxygenation of the ocean-atmosphere system and the radiation of the complex Ediacaran-Cambrian life.

  2. Rapid thermal anneal of arsenic implanted silicon

    Energy Technology Data Exchange (ETDEWEB)

    Feygenson, A.

    1985-01-01

    The distribution of arsenic implanted into silicon during rapid thermal anneal (RTA) was investigated. Secondary ion mass spectrometry, Rutherford backscattering spectrometry, and channeling techniques were used for the measurement of the total (chemical) dopant profile. The electrically active dopant profiles were measured with sheet resistance, sheet-resistance maps, spreading resistance and pinch resistors. It was found that arsenic profile after RTA is influenced by many parameters including crystallographic orientation of the sample, temperature gradient, and defect structure in the surface part affected by heavy arsenic implant. A diffusion model based on inhomogeneous medium was examined. Exact solutions of the diffusion equation were obtained for the rectangular and Gaussian initial dopant profiles. Calculated results are compared to the measured profiles. It is concluded that model satisfactory predicts the major features of the arsenic diffusion into silicon during RTA.

  3. Rapid Thermal Anneal of Arsenic Implanted Silicon.

    Science.gov (United States)

    Feygenson, Anatoly

    1985-12-01

    The distribution of arsenic implanted into silicon during rapid thermal anneal (RTA) has been investigated. Secondary ion mass spectrometry (SIMS), Rutherford backscattering spectrometry (RBS) and channeling techniques were used for the measurement of the total (chemical) dopant profile. The electrically active dopant profiles were measured with sheet resistance, sheet resistance maps, spreading resistance, and pinch resistors. It has been found that arsenic profile after RTA is influenced by many parameters including crystallographic orientation of the sample, temperature gradient, and defect structure in the surface part affected by heavy arsenic implant. A diffusion model based on inhomogeneous medium was examined. Exact solutions of the diffusion equation were obtained for the rectangular and Gaussian initial dopant profiles. Calculated results are compared to the measured profiles. It is concluded that model satisfactory predicts the major features of the arsenic diffusion into silicon during RTA.

  4. Synergistic Synthetic Biology: Units in Concert.

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  5. Arsenic: Not So Evil After All?

    Science.gov (United States)

    Lykknes, Annette; Kvittingen, Lise

    2003-05-01

    This article presents parts of the history of the element arsenic in order to illustrate processes behind development of knowledge in chemistry. The particular aspects presented here are the use of arsenic as a stimulant by Styrian peasants, in Fowler's solution, in drugs of the 19th century (e.g., salvarsan), and in current medical treatment, all of which challenge the myth of this element as exclusively poisonous.

  6. Biosensors for Inorganic and Organic Arsenicals

    Science.gov (United States)

    Chen, Jian; Rosen, Barry P.

    2014-01-01

    Arsenic is a natural environmental contaminant to which humans are routinely exposed and is strongly associated with human health problems, including cancer, cardiovascular and neurological diseases. To date, a number of biosensors for the detection of arsenic involving the coupling of biological engineering and electrochemical techniques has been developed. The properties of whole-cell bacterial or cell-free biosensors are summarized in the present review with emphasis on their sensitivity and selectivity. Their limitations and future challenges are highlighted. PMID:25587436

  7. Arsenic speciation patterns in freshwater fish.

    Science.gov (United States)

    Slejkovec, Zdenka; Bajc, Zlatka; Doganoc, Darinka Z

    2004-04-19

    Muscle of 16 freshwater fish (9 different species belonging to 4 different families) was analysed for arsenic species using HPLC separation (anion and cation exchange) followed by on-line UV-decomposition, hydride generation and AFS detection. The main arsenic compounds found in the extracts were arsenobetaine (AsB), which accounted for 92-100% of extractable arsenic in species of salmonids (Salmo marmoratus, Oncorhynchus mykiss, Salmo trutta m. fario), and dimethylarsinic acid (DMAA), which accounted for 75% of extractable arsenic in burbot (Lota lota). AsB was also found in lower concentrations in almost all other fish species analysed (Silurus glanis, L. lota, Barbus barbus, Rutilus pigus virgo, Chondrostoma nasus). Arsenite (As(III)) and trimethylarsine oxide (TMAO) were detected in low concentrations in some representatives of Cyprinidae only (R. pigus virgo, C. nasus). Except in salmonids, an unknown cationic compound was present in most of the samples in relatively low concentrations. Cluster analysis of the generated data seems to indicate that there is a correlation between fish family and the arsenic speciation pattern. This is especially clear for the salmonids which show a completely separate cluster and thus a very distinct arsenic speciation pattern.

  8. Disruption of Mitotic Progression by Arsenic.

    Science.gov (United States)

    States, J Christopher

    2015-07-01

    Arsenic is an enigmatic xenobiotic that causes a multitude of chronic diseases including cancer and also is a therapeutic with promise in cancer treatment. Arsenic causes mitotic delay and induces aneuploidy in diploid human cells. In contrast, arsenic causes mitotic arrest followed by an apoptotic death in a multitude of virally transformed cells and cancer cells. We have explored the hypothesis that these differential effects of arsenic exposure are related by arsenic disruption of mitosis and are differentiated by the target cell's ability to regulate or modify cell cycle checkpoints. Functional p53/CDKN1A axis has been shown to mitigate the mitotic block and to be essential to induction of aneuploidy. More recent preliminary data suggest that microRNA modulation of chromatid cohesion also may play a role in escape from mitotic block and in generation of chromosomal instability. Other recent studies suggest that arsenic may be useful in treatment of solid tumors when used in combination with other cytotoxic agents such as cisplatin.

  9. Earthworms produce phytochelatins in response to arsenic.

    Directory of Open Access Journals (Sweden)

    Manuel Liebeke

    Full Text Available Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such as cadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are also present in animal species from several different phyla, but there is still little known about whether these genes are functional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by direct chemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenic clearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure the phytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase gene expression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A further untargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway, which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biological transformation of arsenic (e.g. into methylated species as a result of laboratory arsenic exposure. Finally, we compared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated and cadmium-contaminated mine site worms had elevated phytochelatin concentrations.

  10. Earthworms produce phytochelatins in response to arsenic.

    Science.gov (United States)

    Liebeke, Manuel; Garcia-Perez, Isabel; Anderson, Craig J; Lawlor, Alan J; Bennett, Mark H; Morris, Ceri A; Kille, Peter; Svendsen, Claus; Spurgeon, David J; Bundy, Jacob G

    2013-01-01

    Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such as cadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are also present in animal species from several different phyla, but there is still little known about whether these genes are functional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by direct chemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenic clearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure the phytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase gene expression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A further untargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway, which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biological transformation of arsenic (e.g. into methylated species) as a result of laboratory arsenic exposure. Finally, we compared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated and cadmium-contaminated mine site worms had elevated phytochelatin concentrations.

  11. A novel arsenic methyltransferase gene of Westerdykella aurantiaca isolated from arsenic contaminated soil: phylogenetic, physiological, and biochemical studies and its role in arsenic bioremediation.

    Science.gov (United States)

    Verma, Shikha; Verma, Pankaj Kumar; Meher, Alok Kumar; Dwivedi, Sanjay; Bansiwal, Amit Kumar; Pande, Veena; Srivastava, Pankaj Kumar; Verma, Praveen Chandra; Tripathi, Rudra Deo; Chakrabarty, Debasis

    2016-03-01

    Elevated arsenic concentration in the environment and agricultural soil is a serious concern to crop production and human health. Among different detoxification mechanisms, the methylation of arsenic is a widespread phenomenon in nature. A number of microorganisms are able to methylate arsenic, but less is known about the arsenic metabolism in fungi. We identified a novel arsenic methyltransferase (WaarsM) gene from a soil fungus, Westerdykella aurantiaca. WaarsM showed sequence homology with all known arsenic methyltransferases having three conserved SAM binding motifs. The expression of WaarsM enhanced arsenic resistance in E. coli (Δars) and S. cerevisiae (Δacr2) strains by biomethylation and required endogenous reductants, preferably GSH, for methyltransferase activity. The purified WaarsM catalyzes the production of methylated arsenicals from both AsIII and AsV, and also displays AsV reductase activity. It displayed higher methyltransferase activity and lower KM 0.1945 ± 0.021 mM and KM 0.4034 ± 0.078 mM for AsIII and AsV, respectively. S. cerevisiae (Δacr2) cells expressing WaarsM produced 2.2 ppm volatile arsenic and 0.64 ppm DMA(v) with 0.58 ppm volatile arsenicals when exposed to 20 ppm AsV and 2 ppm AsIII, respectively. Arsenic tolerance in rice after co-culture with genetically engineered yeast suggested its potential role in arsenic bioremediation. Thus, characterization of WaarsM provides a potential strategy to reduce arsenic concentration in soil with reduced arsenic accumulation in crops grown in arsenic contaminated areas, and thereby alleviating human health risks.

  12. Effects of arsenic on nitrogen metabolism in arsenic hyperaccumulator and non-hyperaccumulator ferns

    Science.gov (United States)

    This study investigated the effects of arsenic on the in vitro activities of the enzymes (nitrate reductase and nitrite reductase) involved in nitrate metabolism in the roots, rhizomes, and fronds of two four-month old fern plants, Pteris vittata, an arsenic-hyperaccumulator, and Pteris ensiformis, ...

  13. Microbial transformations of arsenic: perspectives for biological removal of arsenic from water

    NARCIS (Netherlands)

    Cavalca, L.; Corsini, A.; Zaccheo, P.; Andreoni, V.; Muyzer, G.

    2013-01-01

    Arsenic is present in many environments and is released by various natural processes and anthropogenic actions. Although arsenic is recognized to cause a wide range of adverse health effects in humans, diverse bacteria can metabolize it by detoxification and energy conservation reactions. This revie

  14. Evidence against the nuclear in situ binding of arsenicals-oxidative stress theory of arsenic carcinogenesis

    Science.gov (United States)

    A large amount of evidence suggests that arsenicals act via oxidative stress in causing cancer in humans and experimental animals. It is possible that arsenicals could bind in situ close to nuclear DNA followed by Haber-Weiss type oxidative DNA damage. Therefore, we tested this...

  15. Role of complex organic arsenicals in food in aggregate exposure to arsenic

    Science.gov (United States)

    For much of the world’s population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels has been linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is impo...

  16. Exposure to inorganic arsenic in soil increases urinary inorganic arsenic concentrations of residents living in old mining areas.

    Science.gov (United States)

    Hinwood, Andrea L; Sim, Malcolm R; Jolley, Damien; de Klerk, Nick; Bastone, Elisa B; Gerostamoulos, Jim; Drummer, Olaf H

    2004-03-01

    The short term human exposure studies conducted on populations exposed to high concentrations of inorganic arsenic in soil have been inconsistent in demonstrating a relationship between environmental concentrations and exposure measures. In Australia there are many areas with very high arsenic concentrations in residential soil most typically associated with gold mining activities in rural areas. This study aimed to investigate the relationship between environmental arsenic and urinary inorganic arsenic concentrations in a population living in a gold mining area (soil arsenic concentrations between 9 and 9900 mg kg(-1)), and a control population with low arsenic levels in soil (between 1 and 80 mg kg(-1)). Risk factors for increased urinary arsenic concentrations were also explored. There was a weak but significant relationship between soil arsenic concentrations and inorganic urinary arsenic concentration with a Spearman correlation coefficient of 0.39. When participants with greater than 100 mg kg(-1) arsenic in residential soil were selected, the coefficient increased to 0.64. The geometric mean urinary inorganic arsenic concentration for the exposed group was 1.64 microg L(-1) (risk factors. These results show that high concentrations of arsenic in soil can make a contribution to urinary inorganic arsenic concentrations.

  17. Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

    Science.gov (United States)

    Piñol, S; Sala, A; Guzman, C; Marcos, S; Joya, X; Puig, C; Velasco, M; Velez, D; Vall, O; Garcia-Algar, O

    2015-11-01

    Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries.

  18. Detection of arsenic ions with preliminary concentrating on magnetic sorbent

    OpenAIRE

    Kharlyamov, Damir; Dvoryak, Stanislav; Mavrin, Gennady

    2013-01-01

    In represented work a method of arsenic ions concentrating is presented by means of sorption with application of synthetic magnetite, which is successfully used for atomic absorption detection of arsenic in natural waters.

  19. Arsenic uptake by Lemna minor in hydroponic system.

    Science.gov (United States)

    Goswami, Chandrima; Majumder, Arunabha; Misra, Amal Kanti; Bandyopadhyay, Kaushik

    2014-01-01

    Arsenic is hazardous and causes several ill effects on human beings. Phytoremediation is the use of aquatic plants for the removal of toxic pollutants from external media. In the present research work, the removal efficiency as well as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic concentration in water samples and plant biomass were determined by AAS. The relative growth factor of Lemna minor was determined. The duckweed had potential to remove as well as uptake arsenic from the aqueous medium. Maximum removal of more than 70% arsenic was achieved atinitial concentration of 0.5 mg/1 arsenic on 15th day of experimental period of 22 days. Removal percentage was found to decrease with the increase in initial concentration. From BCF value, Lemna minor was found to be a hyperaccumulator of arsenic at initial concentration of 0.5 mg/L, such that accumulation decreased with increase in initial arsenic concentration.

  20. Arsenic and the Epigenome: Linked by Methylation(SOT)

    Science.gov (United States)

    Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically-exposed individuals are susceptible to arsenic poisoning, or arsenicosis. In some exposed populations arsenicosis susceptibility is dependent in part on the abil...

  1. [Pathways of arsenic uptake in prokaryotic and eukaryotic cells].

    Science.gov (United States)

    Lis, Paweł; Litwin, Ireneusz; Maciaszczyk-Dziubińska, Ewa

    2010-01-01

    Mechanisms of arsenic uptake and detoxification are present in all studied organisms. These mechanisms are considerably well described in unicellular organisms such as bacterium Escherichia coli and baker's yeast Saccharomyces cerevisiae, still leaving much to be revealed in multicellular organisms. Full identification of arsenic uptake and detoxification is of great importance. This knowledge can be very helpful in improving effectiveness of arsenic-containing drugs used in chemotherapy of parasitoses as well as in treatment of acute promielyocytic leukemia. Increased proficiency of bioremediation of arsenic-contaminated soils can be obtained by using plants hyperaccumulating arsenic. This kind of plants can be engineered by modulating expression levels of genes encoding arsenic transporters. The same technique may be used to decrease levels of accumulated arsenic in crops. The aim of this paper is to review current knowledge about systems of arsenic uptake in every studied organism--from bacteria to human.

  2. Map of Arsenic concentrations in groundwater of the United States

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The map graphic image at http://water.usgs.gov/GIS/browse/arsenic_map.png illustrates arsenic values, in micrograms per liter, for groundwater samples from about...

  3. Mouse Assay for Determination of Arsenic Bioavailability in Contaminated Soils

    Science.gov (United States)

    Background: Accurate assessment of human exposure estimates from arsenic-contaminated soils depends upon estimating arsenic (As) soil bioavailability. Development of bioavailability assays provides data needed for human health risk assessments and supports development and valida...

  4. Uptake of Arsenic in Rice Plant Varieties Cultivated with Arsenic Rich Groundwater

    Directory of Open Access Journals (Sweden)

    Piyal Bhattacharya

    2010-07-01

    Full Text Available Groundwater of many areas of West Bengal, India is severely contaminated with arsenic. The paddy soil gets con¬taminated from the groundwater and thus there is a probability of bioaccumulation of arsenic in rice plants cultivated with arsenic contaminated groundwater and soil. This study aims at assessing the level of arsenic in irrigation water and soil and to investigate the seasonal bioaccumulation of arsenic in the various parts (straw, husk and grain of the rice plant of differ¬ent varieties in the arsenic affected two blocks (Chakdaha and Ranaghat-I of Nadia district, West Bengal. It was found that the arsenic uptake in rice during the pre-monsoon season is more than that of the post-monsoon season. The accumulation of arsenic found to vary with different rice varieties; the maximum accumulation was in White minikit (0.31±0.005 mg/kg and IR 50 (0.29±0.001 mg/kg rice varieties and minimum was found to be in the Jaya rice variety (0.14±0.002 mg/kg. In rice plant maximum arsenic accumulation occurred in the straw part (0.89±0.019-1.65±0.021 mg/kg compared to the ac¬cumulation in husk (0.31±0.011-0.85±0.016 mg/kg and grain (0.14±0.002-0.31±0.005 mg/kg parts. For any rice sample concentration of arsenic in the grain did not exceed the WHO recommended permissible limit in rice (1.0 mg/kg.

  5. Clinical manifestations and arsenic methylation after a rare subacute arsenic poisoning accident.

    Science.gov (United States)

    Xu, Yuanyuan; Wang, Yi; Zheng, Quanmei; Li, Bing; Li, Xin; Jin, Yaping; Lv, Xiuqiang; Qu, Guang; Sun, Guifan

    2008-06-01

    One hundred and four workers ingested excessive levels of arsenic in an accident caused by leakage of pipeline in a copper-smelting factory. Clinical examinations were performed by physicians in a local hospital. Excreted urinary arsenic species were determined by cold trap hydride generation atomic absorption spectrometry. In the initial toxic phase, gastrointestinal symptoms were predominant (83 people, 79.8%). Most patients showed leucopenia (72 people, 69.2%), and increased serum alanine aminotransferase (84 people, 80.8%) and aspartate aminotransferase (58 people, 55.8%). Thirty-five patients (33.6%) had elevated red blood cells in urine. After 17 days of admission, many subjects (45 people, 43.3%) developed peripheral neuropathy and 25 of these 45 patients (24.0%) showed a decrease in motor and sensory nerve conduction velocity. In the comparison of urinary arsenic metabolites among subacute arsenic-poisoned, chronic high arsenic-exposed and control subjects, we found that subacute arsenic-poisoned patients had significantly elevated proportions of urinary inorganic arsenic (iAs) and methylarsonic acid (MMA) but reduced proportion of urinary dimethylarsinic acid (DMA) compared with chronic high arsenic-exposed and control subjects. Chronic exposed subjects excreted higher proportions of iAs and MMA but lower proportions of DMA in urine compared with control subjects. These results suggest that gastrointestinal symptoms, leucopenia, and hepatic and urinary injury are predominant in the initial phase of subacute arsenic poisoning. Peripheral neuropathy is the most frequent manifestation after the initial phase. The biomethylation of arsenic decreases in a dose rate-dependent manner.

  6. Enhancement of chromosomal damage by arsenic: implications for mechanism.

    OpenAIRE

    1993-01-01

    Arsenic is a naturally occurring metalloid that has been associated with increased incidence of human cancer in certain highly exposed populations. Arsenic is released to the environment by natural means such as solubilization from geologic formations into water supplies. It is also released to occupational and community environments by such activities as nonferrous ore smelting and combustion of fuels containing arsenic. Several lines of evidence indicate that arsenic acts indirectly with ot...

  7. Solid materials for removing arsenic and method thereof

    Science.gov (United States)

    Coronado, Paul R.; Coleman, Sabre J.; Sanner, Robert D.; Dias, Victoria L.; Reynolds, John G.

    2008-07-01

    Solid materials have been developed to remove arsenic compounds from aqueous media. The arsenic is removed by passing the aqueous phase through the solid materials which can be in molded, granular, or powder form. The solid materials adsorb the arsenic leaving a purified aqueous stream. The materials are aerogels or xerogels and aerogels or xerogels and solid support structure, e.g., granulated activated carbon (GAC), mixtures. The species-specific adsorption occurs through specific chemical modifications of the solids tailored towards arsenic.

  8. Removal of arsenic from aqueous solution using electrocoagulation.

    Science.gov (United States)

    Balasubramanian, N; Kojima, Toshinori; Basha, C Ahmed; Srinivasakannan, C

    2009-08-15

    Removal of arsenic from aqueous solution was carried out using electrocoagulation. Experiments were conducted using mild steel sacrificial anode covering wide range in operating conditions to assess the removal efficiency. The maximum arsenic removal efficiency was recorded as 94% under optimum con