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Sample records for arsenic trioxide anticancer

  1. Tetrandrine enhances the anticancer effects of arsenic trioxide in vitro.

    PubMed

    Chen, Youran; Li, Peichun; Yang, Shen; Tong, Nannan; Zhang, Jie; Zhao, Xiaoyan

    2014-05-01

    Arsenic trioxide (As2O3), an effective agent to treat leukemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden death have been implicated in the cardiotoxicity of As2O3. The present study was designed to assess whether the combination of As2O3 and tetrandrine could generate a more powerful anti-cancer effect. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed for detecting the proliferation of HepG2 and A549 cells treated with tetrandrine and As2O3. Fluorescent microscopy measurements and flow cytometry were carried out to evaluate the apoptosis in HepG2 cells. The cell cycle arrest of HepG2 cells was also determined by flow cytometry. The cell proliferation assay in HepG2 and A549 cells indicated that tetrandrine significantly enhanced the inhibit effect of As2O3. In addition, the following Isobolograms further demonstrated that combining As2O3 with tetrandrine generated synergism action. Tetrandrine also enhanced the apoptosis, necrosis and cell cycle arrest in As2O3-treated HepG2 cells. Our present study showed that tetrandrine can dramatically enhance the anti- cancer effect induced by As2O3. Combining As2O3 with tetrandrine would be a novel strategy to treat cancer in clinical practice. PMID:24548979

  2. Arsenic Trioxide Injection

    MedlinePlus

    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 ...

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

    NASA Astrophysics Data System (ADS)

    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

  4. Arsenic Trioxide-Induced Mandibular Osteomyelitis.

    PubMed

    Lu, Pei-Chen; Wu, Ju-Hui; Chen, Chun-Ming; Du, Je-Kang

    2015-09-01

    Previously, arsenic was a popular devitalizing agent used to necrotize inflamed dental pulp to lower the pulp sensitivity owing to the unavailability of appropriate anesthesia. However, leakage from the apical foramen, lateral or accessory canals, or cracks in the tooth is common. This can be dangerous because of the reportedly high toxic effects of arsenic in both hard and soft tissues, leading to gingival and osseous necrosis and, consequently, osteomyelitis. Therefore, arsenic can prove fatal for both bones and teeth and is no longer used. We encountered a case involving a 50-year-old man who had developed mandibular osteomyelitis with lower lip paresthesia caused by arsenic trioxide used during endodontic treatment. The patient was treated with appropriate antibiotics, adjunctive hyperbaric oxygen therapy, and adequate surgical debridement. Hyperbaric oxygen therapy can induce neovascularization in necrosed tissues and improve bone and soft tissue healing. At a 4-year follow-up visit, bone healing was observed, with restoration of periodontal health, although the paresthesia had persisted. We describe this case, present a review of the relevant published data, and discuss the possible causes, diagnosis, treatment, and follow-up protocol of mandibular osteomyelitis caused by arsenic trioxide. PMID:25896568

  5. Arsenic Trioxide Negatively Affects Echinococcus granulosus

    PubMed Central

    Wang, Bo; Wang, Zhuo; Li, Fangfang; Xing, Guoqiang; Peng, Xinyu; Zhang, Shijie

    2015-01-01

    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. PMID:26324279

  6. Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide

    PubMed Central

    Sertel, Serkan; Tome, Margaret; Briehl, Margaret M.; Bauer, Judith; Hock, Kai; Plinkert, Peter K.; Efferth, Thomas

    2012-01-01

    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 IC50 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. PMID:22590507

  7. EFFECTS OF ARSENIC TRIOXIDE INHALATION EXPOSURE ON PULMONARY ANTIBACTERIAL DEFENSES IN MICE

    EPA Science Inventory

    The effects of single and multiple (5 and 20) 3 hr inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0.4 microme...

  8. Use of arsenic trioxide in a hemodialysis-dependent patient with relapsed acute promyelocytic leukemia.

    PubMed

    Perreault, Sarah; Moeller, Julie; Patel, Kejal; Eyler, Rachel; Pham, Trinh; Russell, Kerry; Podoltsev, Nikolai

    2016-08-01

    Arsenic trioxide has been established for use in both relapsed and front-line treatment of acute promyelocytic leukemia. Dose adjustments are recommended to be considered in severe renal impairment although dosage reduction guidelines are not provided. In addition, toxicities of arsenic are significant. The use of arsenic trioxide has not been well studied in dialysis patients and there is a paucity of data in the literature to support the use in such a situation. We describe an 81-year-old relapsed acute promyelocytic leukemia hemodialysis-dependent patient with a pre-existing cardiac condition who was treated with 10 mg arsenic trioxide three times weekly after dialysis. These findings provide support along with the marginal amount of currently published data for an arsenic trioxide dosing regimen in hemodialysis patients. PMID:25972392

  9. Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells.

    PubMed

    King, Yih-An; Chiu, Yu-Jen; Chen, Hao-Ping; Kuo, Daih-Huang; Lu, Chi-Cheng; Yang, Jai-Sing

    2016-03-01

    Arsenic trioxide is an old drug and has been used for a long time in traditional Chinese and Western medicines. However, the cancer treatment of arsenic trioxide has heart and vascular toxicity. The cytotoxic effects of arsenic trioxide and its molecular mechanism in human umbilical mesenchymal stem cells (HUMSC) and human bone marrow-derived mesenchymal stem cells (HMSC-bm) were investigated in this study. Our results showed that arsenic trioxide significantly reduced the viability of HUMSC and HMSC-bm in a concentration- and time-dependent manner. Arsenic trioxide is able to induce apoptotic cell death in HUMSC and HMSC-bm, as shown from the results of morphological examination, flow cytometric analyses, DAPI staining and comet assay. The appearance of arsenic trioxide also led to an increase of intracellular free calcium (Ca(2+) ) concentration and the disruption of mitochondrial membrane potential (ΔΨm). The caspase-9 and caspase-3 activities were time-dependently increased in arsenic trioxide-treated HUMSC and HMSC-bm. In addition, the proteomic analysis and DNA microarray were carried out to investigate the expression level changes of genes and proteins affected by arsenic trioxide treatment in HUMSC. Our results suggest that arsenic trioxide induces a prompt induction of ER stress and mitochondria-modulated apoptosis in HUMSC and HMSC-bm. A framework was proposed for the effect of arsenic trioxide cytotoxicity by targeting ER stress. PMID:25258189

  10. Hyperoside enhances the suppressive effects of arsenic trioxide on acute myeloid leukemia cells

    PubMed Central

    Zhang, Feng; Zhu, Fang-Bing; Li, Jia-Jia; Zhang, Ping-Ping; Zhu, Jun-Feng

    2015-01-01

    Hyperoside (Hyp) is the chief component of some Chinese herbs which has anticancer effect and the present study is to identify whether it could enhance the anti leukemic properties of arsenic trioxide (As2O3) in acute myeloid leukemia (AML). We provide evidence on the concomitant treatment of HL-60 human AML cells with hyperoside potentiates As2O3-dependent induction of apoptosis. The activation of caspase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27 was assessed by Western blot. Results showed that hyperoside inhibited BAD from phosphorylating, reactivated caspase-9, and increased p27 levels. Importantly, hyperoside demonstrated its induction of autophagy effect by upregulation of LC-II in HL-60 AML cell line. Taken together, hyperoside may serve as a great candidate of concomitant treatment for leukemia; these effects were probably related to induction of autophagy and enhancing apoptosis-inducing action of As2O3. PMID:26629016

  11. Thermal behaviour of arsenic trioxide adsorbed on activated carbon.

    PubMed

    Cuypers, Frederic; De Dobbelaere, Christopher; Hardy, An; Van Bael, Marlies K; Helsen, Lieve

    2009-07-30

    The thermal stability and desorption of arsenic trioxide (As(2)O(3)) adsorbed on activated carbon (AC) was investigated as this phenomenon is expected to influence the arsenic release during low temperature pyrolysis of chromated copper arsenate (CCA) wood waste. Firstly, a thermogravimetric (TG) experiment with arsenolite, an allotropic form of As(2)O(3), was performed. The sample starts to sublime at temperatures lower than 200 degrees C with a sublimation peak temperature of 271 degrees C. Subsequently, TG experiments with samples of As(2)O(3) adsorbed on AC revealed that only very little (max. 6+/-3 wt%) As(2)O(3) was volatilized at temperatures below 280 degrees C, while still 41.6 (+/-5)wt% of the original arsenic concentration was retained at 440 degrees C and 28.5 (+/-3)wt% at 600 degrees C. The major arsenic volatilization occurred between 300 degrees C and 500 degrees C. The kinetic parameters of desorption, activation energy of desorption (E(d)) and pre-exponential factor (A), were determined by fitting an Arrhenius model to the experimental data, resulting in E(d)=69 kJ/mol, A=1.21 x 10(4)s(-1). It can be concluded that the adsorption of As(2)O(3) on AC can contribute to the thermal stabilisation of As(2)O(3). Consequently, during low temperature pyrolysis of CCA wood arsenic release may be prevented by adsorption of As(2)O(3) on the coal-type product formed during the thermal decomposition of the wood. PMID:19136209

  12. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    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. PMID:27158436

  13. Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress.

    PubMed

    Yu, Meiling; Xue, Jiangdong; Li, Yijing; Zhang, Weiqian; Ma, Dexing; Liu, Lian; Zhang, Zhigang

    2013-06-01

    Arsenic trioxide (As(2)O(3)) is an environmental toxicant and a potent antineoplastic agent. Exposure to arsenic causes renal cancer. Resveratrol is a well-known polyphenolic compound that is reported to reduce As(2)O(3)-induced cardiotoxicity. The present study aimed to investigate the effect of resveratrol on As(2)O(3)-induced nephrotoxicity and arsenic metabolism. Chinese Dragon-Li cats were injected with 1 mg/kg As(2)O(3) on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As(2)O(3) treatment. On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney. Urine samples were taken for arsenic speciation. In the resveratrol + As(2)O(3)-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased. The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As(2)O(3)-treated group. These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As(2)O(3)-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As(2)O(3) metabolism. These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity. PMID:23471352

  14. Potassium Bromate Assay by Redox Titrimetry Using Arsenic Trioxide

    PubMed Central

    Smeller, Johanna M.; Leigh, Stefan D.

    2003-01-01

    Bromate, a disinfectant, is one of the analytes of interest in wastewater analysis. Environmental laboratories have a regulatory need for their measurements to be traceable to NIST standards. Bromate is not currently certified as a NIST Standard Reference Material (SRM). Therefore, a traceable assay of potassium bromate (KBrO3) is needed. KBrO3 was dissolved in water and assayed by redox titrimetry using arsenic trioxide (As2O3). A nominal (0.1 g) sample of As2O3 was dissolved in 10 mL of 5 mol/L sodium hydroxide. The solution was acidified with hydrochloric acid and about 95 % of the KBrO3 titrant was added gravimetrically. The end point was determined by addition of dilute (1:3) titrant using an automated titrator. The KBrO3 assay was determined to be 99.76 % ± 0.20 %. The expanded uncertainty considered the titrations of three independently prepared KBrO3 solutions.

  15. Downregulation of thymidylate synthase with arsenic trioxide in lung adenocarcinoma.

    PubMed

    Lam, Sze-Kwan; Mak, Judith Choi-Wo; Zheng, Chun-Yan; Li, Yuan-Yuan; Kwong, Yok-Lam; Ho, James Chung-Man

    2014-06-01

    Thymidylate synthase (TYMS) is an important chemotherapeutic target in non-small cell lung cancer (NSCLC). Arsenic trioxide (ATO) has been shown to suppress TYMS in a colonic cancer model. We examined the effects of TYMS suppression by ATO in lung adenocarcinoma. A panel of 4 lung adenocarcinoma cell lines was used to determine the effects of ATO treatment on cell viability, TYMS expression (protein and mRNA), E2F1 protein expression and TYMS activity. TYMS knockdown and overexpression were performed. Tumor growth inhibition in vivo was studied using a nude mouse xenograft model. ATO showed antiproliferative effects with clinically achievable concentrations (around 1.1-6.9 µM) in 4 lung adenocarcinoma cell lines. Downregulation of TYMS protein and mRNA expression, reduced TYMS activity, and suppressed E2F1 expression were demonstrated in lung adenocarcinoma with ATO. Cell viability was reduced by 15-50% with TYMS knockdown. Overexpression of TYMS led to a 2.7-fold increase in IC50 value with ATO treatment in H358 cells, but not in H23 cells. Using a xenograft model with H358 cell line, relative tumor volume was reduced to 44% that of the control following 8 days of treatment with 7.5 mg/kg ATO, and associated with significant downregulation of TYMS protein expression. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, and is partially mediated by transcriptional downregulation of TYMS. PMID:24691991

  16. Arsenic Trioxide Induces Apoptosis in Human Platelets via C-Jun NH2-Terminal Kinase Activation

    PubMed Central

    Wu, Yicun; Dai, Jin; Zhang, Weilin; Yan, Rong; Zhang, Yiwen; Ruan, Changgeng; Dai, Kesheng

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS) exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK) activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO. PMID:24466103

  17. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    PubMed

    Wu, Yicun; Dai, Jin; Zhang, Weilin; Yan, Rong; Zhang, Yiwen; Ruan, Changgeng; Dai, Kesheng

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS) exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK) activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO. PMID:24466103

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

    PubMed

    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. PMID:26815588

  19. Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells.

    PubMed

    Nishimoto, Shoichi; Suzuki, Toshihiro; Koike, Shin; Yuan, Bo; Takagi, Norio; Ogasawara, Yuki

    2016-08-15

    Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, has been shown to activate nuclear transcription factor E2-related factor 2 (Nrf2), which plays a central role in cytoprotective responses to oxidative and electrophilic stress. Recently, the Nrf2-Kelch ECH associating protein 1 (Keap1) pathway has been associated with cancer drug resistance attributable to modulation of the expression and activation of antioxidant and detoxification enzymes. However, the exact mechanisms by which Nrf2 activation results in chemoresistance are insufficiently understood to date. This study investigated the mechanisms by which the cytotoxic effects of arsenic trioxide (ATO), an anticancer drug, were decreased in acute promyelocytic leukemia cells treated with CA, a typical activator of Nrf2 used to stimulate the Nrf2/Keap1 system. Our findings suggest that arsenic is non-enzymatically incorporated into NB4 cells and forms complexes that are dependent on intracellular glutathione (GSH) concentrations. In addition, the arsenic complexes are recognized as substrates by multidrug resistance proteins and subsequently excreted from the cells. Therefore, Nrf2-associated activation of the GSH biosynthetic pathway, followed by increased levels of intracellular GSH, are key mechanisms underlying accelerated arsenic efflux and attenuation of the cytotoxic effects of ATO. PMID:27317373

  20. Arsenic trioxide-mediated growth inhibition in gallbladder carcinoma cells via down-regulation of Cyclin D1 transcription mediated by Sp1 transcription factor

    SciTech Connect

    Ai, Zhilong; Lu, Weiqi; Ton, Saixiong; Liu, Houbao; Sou, Tao; Shen, Zhenbin; Qin, Xinyu . E-mail: smc_jjh@yahoo.com.cn

    2007-08-31

    Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of drug stimuli. Here, we demonstrated that arsenic trioxide inhibited the proliferation of gallbladder carcinoma in vivo and in vitro as well as the transcription of cell cycle-related protein Cyclin D1. And, Cyclin D1 overexpression inhibited the negative role of arsenic trioxide in cell cycle progression. We further explored the mechanisms by which arsenic trioxide affected Cyclin D1 transcription and found that the Sp1 transcription factor was down-regulated by arsenic trioxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggested that arsenic trioxide inhibited gallbladder carcinoma cell proliferation via down-regulation of Cyclin D1 transcription in a Sp1-dependent manner, which provided a new mechanism of arsenic trioxide-involved cell proliferation and may have important therapeutic implications in gallbladder carcinoma patients.

  1. Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

    SciTech Connect

    Aranyi, C.; Bradof, J.N.; O'Shea, W.J.; Graham, J.A.; Miller, F.J.

    1985-01-01

    The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0. 4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to /sup 35/S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

  2. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway.

    PubMed

    Mao, Jiamin; Yang, Jianbing; Zhang, Yan; Li, Ting; Wang, Cheng; Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang; Nie, Xiaoke; Chen, Gang

    2016-07-15

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. PMID:27174766

  3. Arsenic trioxide and resveratrol show synergistic anti-leukemia activity and neutralized cardiotoxicity.

    PubMed

    Fan, Yuhua; Chen, Meng; Meng, Jia; Yu, Lei; Tu, Yingfeng; Wan, Lin; Fang, Kun; Zhu, Wenliang

    2014-01-01

    Cardiotoxicity is an aggravating side effect of many clinical antineoplastic agents such as arsenic trioxide (As2O3), which is the first-line treatment for acute promyelocytic leukemia (APL). Clinically, drug combination strategies are widely applied for complex disease management. Here, an optimized, cardiac-friendly therapeutic strategy for APL was investigated using a combination of As2O3 and genistein or resveratrol. Potential combinations were explored with respect to their effects on mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity, autophagy, and apoptosis in both NB4 cells and neonatal rat left ventricular myocytes. All experiments consistently suggested that 5 µM resveratrol remarkably alleviates As2O3-induced cardiotoxicity. To achieve an equivalent effect, a 10-fold dosage of genistein was required, thus highlighting the dose advantage of resveratrol, as poor bioavailability is a common concern for its clinical application. Co-administration of resveratrol substantially amplified the anticancer effect of As2O3 in NB4 cells. Furthermore, resveratrol exacerbated oxidative stress, mitochondrial damage, and apoptosis, thereby reflecting its full range of synergism with As2O3. Addition of 5 µM resveratrol to the single drug formula of As2O3 also further increased the expression of LC3, a marker of cellular autophagy activity, indicating an involvement of autophagy-mediated tumor cell death in the synergistic action. Our results suggest a possible application of an As2O3 and resveratrol combination to treat APL in order to achieve superior therapeutics effects and prevent cardiotoxicity. PMID:25144547

  4. Swallowing a bitter pill-oral arsenic trioxide for acute promyelocytic leukemia.

    PubMed

    Torka, Pallawi; Al Ustwani, Omar; Wetzler, Meir; Wang, Eunice S; Griffiths, Elizabeth A

    2016-05-01

    Parenteral arsenic trioxide (ATO) has been firmly established as a standard therapy for acute promyelocytic leukemia (APL). Despite widespread use of oral arsenicals in medicine historically, they had disappeared from modern pharmacopeia until oral ATO was redeveloped in Hong Kong in 2000. Since then, over 200 patients with leukemia (predominantly APL) have been treated with oral ATO in Hong Kong and China. Oral arsenic trioxide and other formulations of arsenic appear to have a clinical efficacy comparable to that of IV formulations. These drugs given orally also appear to have a slightly better safety profile, lower operational costs and improved convenience for patients. The clinical experience with oral ATO has previously been reported piecemeal as case series, pilot studies or subgroup analyses rather than in a comprehensive cohort. In this report we attempt to synthesize the published English language literature on oral arsenicals and present the argument for further development of these compounds. Systematic study of this drug with well-designed randomized multi-center clinical trials is needed to accelerate its development and incorporation into clinical practice. PMID:26709030

  5. Evaluation of the change in sphingolipids in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 treated with arsenic trioxide.

    PubMed

    Zou, Jianhua; Ma, Xiaoqiong; Zhang, Guangji; Shen, Li; Zhou, Liting; Yu, Yu; Zhu, Fanfan; Chen, Zhe

    2015-11-01

    Arsenic trioxide (As2O3) has been found to display anticancer activity against many types of tumors and has been developed into an anticancer drug in clinical treatments. Sphingolipids are membrane lipids that participate in many signal transduction pathways. In this paper, the changes in sphingolipids of the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803 treated with arsenic trioxide were investigated using an HPLC-ESI-MS/MS method. Analytes were separated by an XBridge BEH C8 column used for Cer, HexCer, LacCer and SM chromatographic separation, and a Capcell PAK MG II C18 column was used for Sph, dhSph, S1P and dhS1P chromatographic separation and gradient elution with acetonitrile-water containing 0.1% formic acid as a mobile phase. A tandem mass spectrometer QTrap in SRM mode was employed in combination with RPLC as a detector for quantitative analysis. The ceramide/sphingolipid internal standard (IS) mixture was used to quantify the levels of sphingolipids. The distributions of sphingolipids were found to be different in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803. Ceramide (Cer), hexosylceramide (HexCer) and dihexosylceramide (Hex2Cer) levels in U266 cell line are higher than those in MGC-803 cell line. Additionally, sphingomyelin (SM), sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (dhS1P) levels in the MGC-803 cell line are higher than those in the U266 cell line. When treated with arsenic trioxide (1-5μM iAs(III)(As(III) ions)), the levels of Hex2Cer in the human multiple myeloma cell line U266 decreased, and the levels of S1P and dhS1P in the human gastric cancer cell line MGC-803 decreased. The decrease of Hex2Cer, S1P and dhS1P in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 were observed when the concentration of iAs(III) is 1.0μM. Therefore, arsenic trioxide exhibits anti-cancer activity by altering the sphingolipid pathway in the

  6. Evaluation of the prenatal developmental toxicity of orally administered arsenic trioxide in rats.

    PubMed

    Holson, J F; Stump, D G; Clevidence, K J; Knapp, J F; Farr, C H

    2000-05-01

    A thorough review of the literature revealed no published repeated-dose oral developmental toxicity studies of inorganic arsenic in rats. In the present study, which was conducted according to modern regulatory guidelines, arsenic trioxide was administered orally beginning 14 days prior to mating and continuing through mating and gestation until gestational day 19. Exposures began prior to mating in an attempt to achieve a steady state of arsenic in the bloodstream of dams prior to embryo-foetal development. Groups of 25 Crl:CD(SD)BR female rats received doses of 0, 1, 2.5, 5 or 10mg/kg/day by gavage. The selection of these dose levels was based on a preliminary range-finding study, in which excessive post-implantation loss and markedly decreased foetal weight occurred at doses of 15 mg/kg/day and maternal deaths occurred at higher doses. Maternal toxicity in the 10mg/kg/day group was evidenced by decreased food consumption and decreased net body weight gain during gestation, increased liver and kidney weights, and stomach abnormalities (adhesions and eroded areas). Transient decreases in food consumption in the 5mg/kg/day group caused the maternal no-observed-adverse-effect level (NOAEL) to be determined as 2. 5mg/kg/day. Intrauterine parameters were unaffected by arsenic trioxide. No treatment-related foetal malformations were noted in any dose group. Increased skeletal variations at 10mg/kg/day were attributed to reduced foetal weight at that dose level. The developmental NOAEL was thus 5mg/kg/day. Based on this study, orally administered arsenic trioxide cannot be considered to be a selective developmental toxicant (i.e. it is not more toxic to the conceptus than to the maternal organism), nor does it exhibit any propensity to cause neural tube defects, even at maternally toxic dose levels. PMID:10762732

  7. Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats.

    PubMed

    Holson, J F; Stump, D G; Ulrich, C E; Farr, C H

    1999-09-01

    A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant. PMID:10496680

  8. Blood biochemistry, thyroid hormones, and oxidant/antioxidant status of guinea pigs challenged with sodium arsenite or arsenic trioxide.

    PubMed

    Mohanta, Ranjan Kumar; Garg, Anil Kumar; Dass, Ram Sharan; Behera, Suvendu Kumar

    2014-08-01

    The present experiment aimed to compare the two most commonly used compounds of arsenic (sodium arsenite and arsenic trioxide) for their effect on blood metabolites, thyroid hormones, and oxidant/antioxidant status in guinea pigs. Twenty-one adult guinea pigs were randomly divided into three equal groups. Animals in group T1 (control) were fed a basal diet, whereas 50 ppm arsenic was added in the basal diet either as sodium arsenite (T2) or arsenic trioxide (T3) and fed for 11 weeks. Serum aspartate aminotransferase and alanine aminotransferase activities were significantly increased along with a decrease in blood hemoglobin level in both the arsenic-administered groups. The level of erythrocytic antioxidants (catalase, superoxide dismutase, reduced glutathione, glutathione-S-transferase, and glutathione reductase) was decreased and lipid peroxidation was elevated upon arsenic exposure. Serum thyroid hormone levels were reduced and arsenic levels in tissues increased in both the arsenic-exposed groups, irrespective of the arsenic compound. Thus, sodium arsenite and arsenic trioxide exerted similar adverse effects on blood metabolic profile, antioxidant status, and thyroid hormones in guinea pigs. PMID:24948398

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

    SciTech Connect

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    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.

  10. Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide

    PubMed Central

    Udensi, Udensi K.; Cohly, Hari H.P.; Graham-Evans, Barbara E.; Ndebele, Kenneth; Garcia-Reyero, Natàlia; Nanduri, Bindu; Tchounwou, Paul B.; Isokpehi, Raphael D.

    2011-01-01

    Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes. PMID:21461292

  11. Gingival and localized alveolar bone necrosis related to the use of arsenic trioxide paste--two case reports.

    PubMed

    Chen, Gin; Sung, Po-Ta

    2014-03-01

    The leakage of arsenic trioxide paste from tooth fillings has been associated with widespread necrosis of the supporting periodontal tissues. This report describes two cases of arsenic trioxide paste-induced gingival and localized alveolar bone necrosis in the mandible, following the use of arsenic trioxide paste as a pulp-devitalized agent. The first case was a 54-year-old female complaining of a painful white patch on the gingival tissue of the left mandibular second molar (tooth #37) after treatment by a private dentist. She underwent completely debridement of all necrotic soft tissue with physical saline irrigation. The gingival tissue was gradually replaced with vascular tissue and completely healed after 7 weeks. The second case was a 30-year-old female complaining of severe pain and continuous gingival bleeding from the right maxillary first bicuspid (tooth #14) following treatment by a private dentist. She finally accepted debridement of the sequestrum and necrotic alveolar bone with decortication to induce active bleeding. A partial thickness gingival flap was made to cover the wound. Four weeks later, the supporting tissues had completely healed. Arsenic trioxide paste is a cytotoxic agent and may cause harmful adverse effects on adjacent periodontium and supporting hard tissue if leakage occurs, or it is used carelessly. There is no indication for the use of arsenic trioxide paste in modern dental practice. PMID:24630037

  12. Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells.

    PubMed

    Yun, Sun-Mi; Woo, Sang Hyeok; Oh, Sang Taek; Hong, Sung-Eun; Choe, Tae-Boo; Ye, Sang-Kyu; Kim, Eun-Kyu; Seong, Min Ki; Kim, Hyun-A; Noh, Woo Chul; Lee, Jin Kyung; Jin, Hyeon-Ok; Lee, Yun-Han; Park, In-Chul

    2016-02-15

    Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells. PMID:26607805

  13. Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells

    SciTech Connect

    Sumi, Daigo; Shinkai, Yasuhiro; Kumagai, Yoshito

    2010-05-01

    Arsenic trioxide (As{sub 2}O{sub 3}) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As{sub 2}O{sub 3} affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As{sub 2}O{sub 3} to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As{sub 2}O{sub 3} exposure in leukemia cells.

  14. Arsenic Trioxide Exposure Induces Heat Shock Protein Responses in Cock Livers.

    PubMed

    Zhang, Kexin; Zhao, Panpan; Guo, Guangyang; Guo, Ying; Li, Siwen; He, Ying; Sun, Xiao; Chai, Hongliang; Zhang, Wen; Xing, Mingwei

    2016-04-01

    Arsenic is a trace element widely found in nature, and there are several forms of arsenic, including the most toxic form of trivalent arsenic. Arsenic trioxide (As2O3) is widespread in nature and tends to accumulate in animals and humans, thus causing great harm. Although the important role of heat shock proteins (HSPs) has been demonstrated in many types of mammals exposed to As2O3, the function of these proteins in poultry, especially in cocks, remains unclear. In this study, we used experimental animals (male chickens), which were fed a diet including 0, 7.5, 15, and 30 mg kg(-1) As2O3, respectively, in the control, low, middle, and high groups. The livers were collected after the cocks were treated with arsenic for 30, 60, and 90 days. We detected HSP27, HSP60, HSP70, and HSP90 levels in the livers of the cocks by real-time PCR and HSP60 and HSP70 levels by Western blot. The results showed that the messenger RNA and protein expression of HSPs exposed to As2O3 had obviously increased. These results demonstrated that arsenic toxicity affected the expression of HSP levels in cock livers. PMID:26329997

  15. A P53 target gene, PIG11, contributes to chemosensitivity of cells to arsenic trioxide.

    PubMed

    Liang, Xiao-Qiu; Cao, En-Hua; Zhang, Yan; Qin, Jing-Fen

    2004-07-01

    The tumor suppressor p53 regulates the expression of various genes that promote apoptosis. PIG11 (P53-induced gene 11), also referred to as TP53I11 (tumor protein p53 inducible protein 11), is a direct p53 target gene. Recent data demonstrated that PIG11 was up-regulated markedly in arsenic trioxide induced apoptosis by DDRT-PCR, suggesting a new class of p53 target genes that sensitize cells to the effects of chemotherapeutic agents. In this study, through the construction of a recombinant GFP-PIG11 expression vector and transfection of HEK293 cells with GFP or GFP-PIG11, the role of PIG11 in apoptosis was analyzed. Results demonstrated that the percentage (11.38%) of apoptotic cells with GFP-PIG11 transfection was higher than that (7.28%) of with only GFP transfection (P<0.05). At 24 h after 1 microM of arsenic trioxide treatment, apoptotic cells exhibited a significant increase in the expression of GFP-PIG11 (36.67%+/-2.78), in contrast, 10.50%+/-2.03 only GFP and 5.25%+/-0.96 vehicle control (P<0.01). In addition, we showed that intracellular content of reactive oxygen species (ROS) was 9.66+/-0.52 in GFP-PIG11 transfection, higher than 5.21+/-0.08 in GFP only and 5.99+/-0.45 in vehicle control (P<0.01). The above results suggest that overexpression of PIG11 could induce cell apoptosis in the low levels and enhanced the apoptotic effects of arsenic trioxide. The process could be involved in intracellular generation of ROS. PMID:15225615

  16. Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma.

    PubMed

    Lam, Sze-Kwan; Li, Yuan-Yuan; Zheng, Chun-Yan; Ho, James Chung-Man

    2015-01-01

    Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a specific siRNA. Phosphatidylserine externalization and mitochondrial membrane depolarization were measured by Annexin V and JC-1 staining respectively. The in vivo effect of ATO was studied using a nude mouse xenograft model. Application of ATO demonstrated anticancer effects in the cell line model with clinically achievable concentrations. Downregulation of TYMS protein (except H226 cells and 1.25 µM ATO in H2052 cells) and mRNA expression (H28 cells), pRB1 (H28 cells) and E2F1 and TYMS activity (except H226 cells) were also evident. E2F1 knockdown decreased cell viability more significantly than TYMS knockdown. In general, thymidine kinase 1, ribonucleotide reductase M1, c-myc and skp2 were downregulated by ATO. p-c-Jun was downregulated in H28 cells while upregulated in 211H cells. Phosphatidylserine externalization, mitochondrial membrane depolarization, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bak and cleaved caspase-3 were observed. In the H226 xenograft model, the relative tumor growth was aborted, and E2F1 was downregulated while cleaved caspase-3 was elevated and localized to the nucleus in the ATO treatment group. ATO has potent antiproliferative and cytotoxic effects in mesothelioma in vitro and in vivo, partially mediated through E2F1 targeting (less effect through TYMS targeting). There is sound scientific evidence to support the

  17. Proteomics-Based Identification of Differentially Abundant Proteins from Human Keratinocytes Exposed to Arsenic Trioxide

    PubMed Central

    Udensi, Udensi K; Tackett, Alan J; Byrum, Stephanie; Avaritt, Nathan L; Sengupta, Deepanwita; Moreland, Linley W; Tchounwou, Paul B; Isokpehi, Raphael D

    2014-01-01

    Introduction Arsenic is a widely distributed environmental toxicant that can cause multi-tissue pathologies. Proteomic assays allow for the identification of biological processes modulated by arsenic in diverse tissue types. Method The altered abundance of proteins from HaCaT human keratinocyte cell line exposed to arsenic was quantified using a label-free LC-MS/MS mass spectrometry workflow. Selected proteomics results were validated using western blot and RT-PCR. A functional annotation analytics strategy that included visual analytical integration of heterogeneous data sets was developed to elucidate functional categories. The annotations integrated were mainly tissue localization, biological process and gene family. Result The abundance of 173 proteins was altered in keratinocytes exposed to arsenic; in which 96 proteins had increased abundance while 77 proteins had decreased abundance. These proteins were also classified into 69 Gene Ontology biological process terms. The increased abundance of transferrin receptor protein (TFRC) was validated and also annotated to participate in response to hypoxia. A total of 33 proteins (11 increased abundance and 22 decreased abundance) were associated with 18 metabolic process terms. The Glutamate--cysteine ligase catalytic subunit (GCLC), the only protein annotated with the term sulfur amino acid metabolism process, had increased abundance while succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial precursor (SDHB), a tumor suppressor, had decreased abundance. Conclusion A list of 173 differentially abundant proteins in response to arsenic trioxide was grouped using three major functional annotations covering tissue localization, biological process and protein families. A possible explanation for hyperpigmentation pathologies observed in arsenic toxicity is that arsenic exposure leads to increased iron uptake in the normally hypoxic human skin. The proteins mapped to metabolic process terms and

  18. Evaluation of a Chemical Fixation Technique for Remediation of Soils Contaminated with Arsenic Trioxide

    NASA Astrophysics Data System (ADS)

    Donahoe, R. J.; Yang, L.; Graham, E. Y.; Redwine, J. C.

    2004-12-01

    The results of an experimental study designed to test a chemical fixation technique for remediation of arsenic-contaminated soils are reported. Soil samples were collected from two industrial sites where herbicide application contaminated the soil with arsenic trioxide. Weathering has redistributed and changed the speciation of the arsenic and caused contamination of soil water and groundwater. Remediation techniques requiring excavation of the affected soil are impractical due to the lack of site access for heavy equipment and the large area impacted. To address these concerns, an in situ treatment method was developed and tested in laboratory experiments. Column experiments were conducted to evaluate the effectiveness of the soil treatment method. Homogenized soil samples from each site were packed into duplicate 4"x18" Plexiglas columns and treated with ferrous sulfate solution using a flow rate of 2 ml/min until iron breakthrough was achieved. Another pair of packed columns was leached with DDI water to provide baseline data for the effect of the treatment solution matrix on arsenic mobility. All soil column effluents showed an initial spike of arsenic after onset of fluid flow; however, the soils undergoing treatment leached less than one half the amount of arsenic leached from the soil by DDI water. When the soil became saturated with the ferrous sulfate treatment solution, effluent solution arsenic concentrations fell below detectable levels. After breakthrough of the treatment solution was achieved, the treated soil columns were allowed to drain and cure for 7 days. One treated soil column and one untreated soil column were then continuously leached with EPA Method 1312 SPLP fluid to observe the effect of treatment on the mobility of arsenic. The second set of treated and untreated soil columns was also leached with SPLP fluid, but in a manner designed to simulate periodic rainfall events. Preliminary experimental results show that ferrous sulfate treatment

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

    SciTech Connect

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    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.

  20. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes.

    PubMed

    Rebuzzini, Paola; Cebral, Elisa; Fassina, Lorenzo; Alberto Redi, Carlo; Zuccotti, Maurizio; Garagna, Silvia

    2015-01-01

    Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 μM). At 0.5 or 1.0 μM the expression of cardiomyocyte marker genes is altered. Even at 0.1 μM, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure. PMID:26447599

  1. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes

    PubMed Central

    Rebuzzini, Paola; Cebral, Elisa; Fassina, Lorenzo; Alberto Redi, Carlo; Zuccotti, Maurizio; Garagna, Silvia

    2015-01-01

    Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 μM) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 μM). At 0.5 or 1.0 μM the expression of cardiomyocyte marker genes is altered. Even at 0.1 μM, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure. PMID:26447599

  2. Synchronization in the Heart Rate and the Vasomotion in Rat Aorta: Effect of Arsenic Trioxide.

    PubMed

    Cifuentes, Fredi; Palacios, Javier; Nwokocha, Chukwuemeka R

    2016-01-01

    Arsenic trioxide (As2O3) is used clinically in the management of acute promyelocytic leukemia, and the use of electrocardiogram (ECG) in this management is important as arsenic use may cause distortion of the electrical properties with its attendant sequel. We studied the effect of As2O3 on vasomotion in rat aortic rings using isometric tension recordings and ECG in anesthetized rats. The results showed that As2O3 (10(-5) M) significantly (p < 0.01) reduced the frequency of acetylcholine (10(-5) M ACh)- and KCl (10 mM)-induced vasomotion, and it also increased the relaxation time (R t) of vasomotion. This effect was restored by 10(-8) M sodium nitroprusside (nitric oxide donor). ACh-induced NO release in the aorta was blunted in the presence of As2O3. The corrected QT interval (QTc) of the ECG, and time dilation (T d) of the pulse wave in the tail artery of the anesthetized rat were significantly (p < 0.05) increased in the arsenic-treated group (50 ppb As) versus control. In conclusion, data suggest that arsenic-induced reduction in vasomotion frequency of the isolated aortic rings is associated with a decreased bioavailability of NO, an increase in QTc and a decrease in the frequency of the pulse wave generated by the cardiac cycle in anesthetized rats. PMID:25666560

  3. Inflammatory Factor Alterations in the Gastrointestinal Tract of Cocks Overexposed to Arsenic Trioxide.

    PubMed

    Xing, Mingwei; Zhao, Panpan; Guo, Guangyang; Guo, Ying; Zhang, Kexin; Tian, Li; He, Ying; Chai, Hongliang; Zhang, Wen

    2015-10-01

    Exposure of people and animals to arsenic (As) is a global public health concern because As is widely distributed and associated with numerous adverse effects. As is a poisonous metalloid and arsenic trioxide (As2O3) is a form of As. Thus far, there have been very few reports on the inflammatory factor alterations of the gastrointestinal tract in birds exposed to As2O3. To investigate the possible correlation of As2O3 with inflammatory injury induced by an arsenic-supplemented diet in birds, 72 1-day-old male Hy-line cocks were selected and randomly divided into four groups. They were fed with either a commercial diet or an arsenic-supplemented diet containing 7.5, 15, and 30 mg/kg As2O3. The experiment lasted for 90 days, and samples of gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum were collected at days 30, 60, and 90 of the experiment period. The inflammation-related genes were determined, including NF-κB, iNOS, COX-2, PTGEs, and TNF-α. The connection between arsenic dosage and inflammation-related genes was assessed. The content of inducible NO synthase (iNOS) was measured by Western blot of the samples. The results showed that arsenic supplementation increased the mRNA expression levels of inflammation-related genes in the gastrointestinal tract of cocks at different time points (p < 0.05). Moreover, the expression of the tissue and organ injury-related gene iNOS was upregulated (p < 0.05). These data suggest that As induces the inflammatory response and may trigger digestive function regression of the gastrointestinal tract by affecting inflammation-related genes and iNOS in cocks. This study offers some information on the mechanism of gastrointestinal tract inflammatory injury and iNOS expression level alterations induced by arseniasis. PMID:25784090

  4. Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma

    PubMed Central

    Ally, Mina S.; Ransohoff, Katherine; Sarin, Kavita; Atwood, Scott X.; Rezaee, Melika; Bailey-Healy, Irene; Kim, Jynho; Beachy, Philip A.; Chang, Anne Lynn S.; Oro, Anthony; Tang, Jean Y.; Colevas, A. Dimitrios

    2016-01-01

    IMPORTANCE Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor–treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. OBJECTIVE To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples. DESIGN, SETTING, AND PARTICIPANTS Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015. MAIN OUTCOMES AND MEASURES The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability. RESULTS Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients. CONCLUSIONS AND RELEVANCE Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing

  5. Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes

    SciTech Connect

    Huang, H.-S.; Liu, Z.-M.; Hong, D.-Y.

    2010-04-15

    Arsenic is well known as a carcinogen predisposing humans to some severe diseases and also as an effective medicine for treating acute promyelocytic leukemia, syphilis, and psoriasis. Multiple active mechanisms, including cell cycle arrest and apoptosis, have been proposed in therapy; however, the opposing effects of arsenic remain controversial. Our previous study found that arsenic trioxide (ATO)-induced activation of p21{sup WAF1/CIP1} (p21) led to A431 cell death through the antagonistic effects of the signaling of ERK1/2 and JNK1. In the current study, the inhibitory effects of JNK1 on ATO-induced p21 expression were explored. Over-expression of JNK1 in A431 cells could inhibit p21 expression, which was associated with HDAC1 and TGIF. Using the GST pull-down assay and fluorescence resonance energy transfer analysis, N-terminal domain (amino acids 1-108) of TGIF, critical to its binding with c-Jun, was found. Using reporter assays, requirement of the C-terminal domain (amino acids 138-272) of TGIF to suppress ATO-induced p21 expression was observed. Thus, the domains of TGIF that carried out its inhibitory effects on p21 were identified. Finally, treatment with JNK inhibitor SP600125 could enhance ATO-induced apoptosis of HaCaT keratinocytes by using flow cytometry.

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

    PubMed Central

    Badarkhe, Girish V.; Sil, Amrita; Bhattacharya, Sabari; Nath, Uttam Kumar; Das, Nilay Kanti

    2016-01-01

    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. PMID:27114640

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

    PubMed

    Badarkhe, Girish V; Sil, Amrita; Bhattacharya, Sabari; Nath, Uttam Kumar; Das, Nilay Kanti

    2016-01-01

    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. PMID:27114640

  8. Enhancement of Arsenic Trioxide-Mediated Changes in Human Induced Pluripotent Stem Cells (IPS)

    PubMed Central

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

    2014-01-01

    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. PMID:25054231

  9. Effects of Arsenic Trioxide Exposure on Heat Shock Protein Response in the Immune Organs of Chickens.

    PubMed

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

    2016-01-01

    Arsenic trioxide (As2O3), a kind of pentavalent arsenic, has recently been linked to disrupted immune function. Heat shock proteins (Hsps), a group of highly conserved proteins, are rapidly synthesised when living organisms are exposed to various stress conditions. The objective of this study is to determine the effects of As2O3 on the expression level of Hsps (Hsp90, Hsp70, Hsp60, Hsp40 and Hsp27) in the immune organs (spleen, thymus and bursa of Fabricius (BF)) of chickens. A total of 72 1-day-old male Hy-line chickens were randomly divided into four groups, including the low-As group (L group), middle-As group (M group), high-As group (H group) and control group (C group). Immune organs were collected, and levels of Hsp messenger RNA (mRNA) and protein were examined on days 30, 60 and 90. The results showed that the levels of Hsp mRNA (Hsp90, Hsp70, Hsp60, Hsp40 and Hsp27) and protein (Hsp70 and Hsp60) expression were significantly increased (p < 0.05 or p < 0.01) in the As2O3 treatment groups compared with the corresponding control groups. Taken together, these results suggest that As2O3 influences the level of Hsps in immune organs. PMID:26050236

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

    PubMed Central

    2010-01-01

    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 understanding the mechanism of

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

    PubMed

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

    2016-12-01

    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. PMID:26887578

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Arsenic trioxide phosphorylates c-Fos to transactivate p21{sup WAF1/CIP1} expression

    SciTech Connect

    Liu Zimiao; Huang, H.-S.

    2008-12-01

    An infamous poison, arsenic also has been used as a drug for nearly 2400 years; in recently years, arsenic has been effective in the treatment of acute promyelocytic leukemia. Increasing evidence suggests that opposite effects of arsenic trioxide (ATO) on tumors depend on its concentrations. For this reason, the mechanisms of action of the drug should be elucidated, and it should be used therapeutically only with extreme caution. Previously, we demonstrated the opposing effects of ERK1/2 and JNK on p21{sup WAF1/CIP1} (p21) expression in response to ATO in A431 cells. In addition, JNK phosphorylates c-Jun (Ser{sup 63/73}) to recruit TGIF/HDAC1 to suppress p21 gene expression. Presently, we demonstrated that a high concentration of ATO sustains ERK1/2 phosphorylation, and increases c-Fos biosynthesis and stability, which enhances p21 gene expression. Using site-directed mutagenesis, a DNA affinity precipitation assay, and functional assays, we demonstrated that phosphorylation of the C-terminus of c-Fos (Thr{sup 232}, Thr{sup 325}, Thr{sup 331}, and Ser{sup 374}) plays an important role in its binding to the p21 promoter, and in conjunction with N-terminus phosphorylation of c-Fos (Ser{sup 70}) to transactivate p21 promoter expression. In conclusion, a high concentration of ATO can sustain ERK1/2 activation to enhance c-Fos expression, then dimerize with dephosphorylated c-Jun (Ser{sup 63/73}) and recruit p300/CBP to the Sp1 sites (- 84/- 64) to activate p21 gene expression in A431 cells.

  14. GENOTOXIC MECHANISMS OF ARSENIC TRIOXIDE IN HUMAN JURKAT T-LYMPHOMA CELLS.

    PubMed

    Yedjou, Clement; Sutton, La'mont; Tchounwou, Paul

    2008-01-01

    Arsenic trioxide (As(2)O(3)) has cytotoxic effects on several cancer cell lines. However, the molecular mechanisms of action remain to be elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by As(2)O(3) in a human Jurkat T-lymphoma cell line using the trypan blue exclusion test and alkaline single cell gel electrophoresis (Comet) assays, respectively. Jurkat T-cells were treated with different doses of As(2)O(3) for 24 and 48 h prior to cytogenetic assessment. Data obtained from the trypan blue exclusion test indicated that As(2)O(3) significantly (p < 0.05) reduced the viability of Jurkat T-cells in a dose and time-dependent manner. Data generated from the comet assay also indicated a significant dose and time-dependent increase in DNA damage in Jurkat T-cells associated with As(2)O(3) exposure. We observed a significant increase (P < 0.05) in comet tail-length, tail arm and tail moment, as well as in percentages of DNA cleavage at all doses tested, showing an evidence As(2)O(3) -induced genotoxic damage in Jurkat T-cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by heavy metals such as arsenic. Taken together, our findings suggest that As(2)O(3) exposure significantly (p < 0.05) reduces cellular viability and induces DNA damage in human Jurkat T-lymphoma cells. PMID:21796259

  15. Arsenic trioxide disrupts glioma stem cells via promoting PML degradation to inhibit tumor growth

    PubMed Central

    Zhou, Wenchao; Cheng, Lin; Shi, Yu; Ke, Susan Q.; Huang, Zhi; Fang, Xiaoguang; Chu, Cheng-wei; Xie, Qi; Bian, Xiu-wu; Rich, Jeremy N.; Bao, Shideng

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal brain tumor. Tumor relapse in GBM is inevitable despite maximal therapeutic interventions. Glioma stem cells (GSCs) have been found to be critical players in therapeutic resistance and tumor recurrence. Therapeutic drugs targeting GSCs may significantly improve GBM treatment. In this study, we demonstrated that arsenic trioxide (As2O3) effectively disrupted GSCs and inhibited tumor growth in the GSC-derived orthotopic xenografts by targeting the promyelocytic leukaemia (PML). As2O3 treatment induced rapid degradation of PML protein along with severe apoptosis in GSCs. Disruption of the endogenous PML recapitulated the inhibitory effects of As2O3 treatment on GSCs both in vitro and in orthotopic tumors. Importantly, As2O3 treatment dramatically reduced GSC population in the intracranial GBM xenografts and increased the survival of mice bearing the tumors. In addition, As2O3 treatment preferentially inhibited cell growth of GSCs but not matched non-stem tumor cells (NSTCs). Furthermore, As2O3 treatment or PML disruption potently diminished c-Myc protein levels through increased poly-ubiquitination and proteasome degradation of c-Myc. Our study indicated a potential implication of As2O3 in GBM treatment and highlighted the important role of PML/c-Myc axis in the maintenance of GSCs. PMID:26510911

  16. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors1

    PubMed Central

    Griffin, Robert J; Lee, Sang H; Rood, Kelly L; Stewart, Michael J; Lyons, John C; Lew, Young S; Park, Heonjoo; Song, Chang W

    2000-01-01

    Abstract 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 TNFα 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. PMID:11228548

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

    PubMed

    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. PMID:26676886

  18. Arsenic trioxide plus PX-478 achieves effective treatment in pancreatic ductal adenocarcinoma.

    PubMed

    Lang, Mingxiao; Wang, Xiuchao; Wang, Hongwei; Dong, Jie; Lan, Chungen; Hao, Jihui; Huang, Chongbiao; Li, Xin; Yu, Ming; Yang, Yanhui; Yang, Shengyu; Ren, He

    2016-08-10

    Arsenic trioxide (ATO) has been selected as a promising treatment not only in leukemia but also in solid tumors. Previous studies showed that the cytotoxicity of ATO mainly depends on the induction of reactive oxygen species. However, ATO has only achieved a modest effect in pancreatic ductal adenocarcinoma, suggesting that the existing radical scavenging proteins, such as hypoxia inducible factor-1, attenuate the effect. The goal of this study is to investigate the effect of combination treatment of ATO plus PX-478 (hypoxia-inducible factor-1 inhibitor) and its underlying mechanism. Here, we showed that PX-478 robustly strengthened the anti-growth and pro-apoptosis effect of ATO on Panc-1 and BxPC-3 pancreatic cancer cells in vitro. Meanwhile, in vivo mouse xenograft models also showed the synergistic effect of ATO plus PX-478 compared with any single agent. Further studies showed that the anti-tumor effect of ATO plus PX-478 was derived from the reactive oxygen species-induced apoptosis. We next confirmed that Hypoxia-inducible factor-1 cleared reactive oxygen species by its downstream target, forkhead box O transcription factors, and this effect may justify the strategy of ATO plus PX-478 in the treatment of pancreatic cancer. PMID:27212442

  19. Role of Signal Regulatory Protein α in Arsenic Trioxide-induced Promyelocytic Leukemia Cell Apoptosis.

    PubMed

    Pan, Chaoyun; Zhu, Dihan; Zhuo, Jianjiang; Li, Limin; Wang, Dong; Zhang, Chen-Yu; Liu, Yuan; Zen, Ke

    2016-01-01

    Signal regulatory protein α (SIRPα) has been shown to operate as a negative regulator in cancer cell survival. The mechanism underneath such function, however, remains poorly defined. In the present study, we demonstrate that overexpression of SIRPα in acute promyelocytic leukemia (APL) cells results in apoptosis possibly via inhibiting the β-catenin signaling pathway and upregulating Foxo3a. Pharmacological activation of β-catenin signal pathway attenuates apoptosis caused by SIRPα. Interestingly, we also find that the pro-apoptotic effect of SIRPα plays an important role in arsenic trioxide (ATO)-induced apoptosis in APL cells. ATO treatment induces the SIRPα protein expression in APL cells and abrogation of SIRPα induction by lentivirus-mediated SIRPα shRNA significantly reduces the ATO-induced apoptosis. Mechanistic study further shows that induction of SIRPα protein in APL cells by ATO is mediated through suppression of c-Myc, resulting in reduction of three SIRPα-targeting microRNAs: miR-17, miR-20a and miR-106a. In summary, our results demonstrate that SIRPα inhibits tumor cell survival and significantly contributes to ATO-induced APL cell apoptosis. PMID:27010069

  20. Role of Signal Regulatory Protein α in Arsenic Trioxide-induced Promyelocytic Leukemia Cell Apoptosis

    PubMed Central

    Pan, Chaoyun; Zhu, Dihan; Zhuo, Jianjiang; Li, Limin; Wang, Dong; Zhang, Chen-Yu; Liu, Yuan; Zen, Ke

    2016-01-01

    Signal regulatory protein α (SIRPα) has been shown to operate as a negative regulator in cancer cell survival. The mechanism underneath such function, however, remains poorly defined. In the present study, we demonstrate that overexpression of SIRPα in acute promyelocytic leukemia (APL) cells results in apoptosis possibly via inhibiting the β-catenin signaling pathway and upregulating Foxo3a. Pharmacological activation of β-catenin signal pathway attenuates apoptosis caused by SIRPα. Interestingly, we also find that the pro-apoptotic effect of SIRPα plays an important role in arsenic trioxide (ATO)-induced apoptosis in APL cells. ATO treatment induces the SIRPα protein expression in APL cells and abrogation of SIRPα induction by lentivirus-mediated SIRPα shRNA significantly reduces the ATO-induced apoptosis. Mechanistic study further shows that induction of SIRPα protein in APL cells by ATO is mediated through suppression of c-Myc, resulting in reduction of three SIRPα-targeting microRNAs: miR-17, miR-20a and miR-106a. In summary, our results demonstrate that SIRPα inhibits tumor cell survival and significantly contributes to ATO-induced APL cell apoptosis. PMID:27010069

  1. Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis

    SciTech Connect

    Wu Yichen; Yen Wenyen; Lee, T.-C. Yih, L.-H.

    2009-04-15

    Arsenic trioxide (ATO) has recently emerged as a promising therapeutic agent in leukemia because of its ability to induce apoptosis. However, there is no sufficient evidence to support its therapeutic use for other types of cancers. In this study, we investigated if, and how, 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), an antagonist of heat shock protein 90 (HSP90), and KNK437, a HSP synthesis inhibitor, potentiated the cytotoxic effect of ATO. Our results showed that cotreatment with ATO and either 17-DMAG or KNK437 significantly increased ATO-induced cell death and apoptosis. siRNA-mediated attenuation of the expression of the inducible isoform of HSP70 (HSP70i) or HSP90{alpha}/{beta} also enhanced ATO-induced apoptosis. In addition, cotreatment with ATO and 17-DMAG or KNK437 significantly increased ATO-induced mitotic arrest and ATO-induced BUBR1 phosphorylation and PDS1 accumulation. Cotreatment also significantly increased the percentage of mitotic cells with abnormal mitotic spindles and promoted metaphase arrest as compared to ATO treatment alone. These results indicated that 17-DMAG or KNK437 may enhance ATO cytotoxicity by potentiating mitotic arrest and mitotic apoptosis possibly through increased activation of the spindle checkpoint.

  2. Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1.

    PubMed

    Lo, Rico K H; Kwong, Yok-Lam

    2014-02-01

    Mantle cell lymphoma (MCL) is aggressive with poor prognosis. Due to t(11;14)(q13;q32), cyclin D1 is overexpressed. The in vitro activities of arsenic trioxide (As2O3) in MCL were investigated. In MCL lines Jeko-1 and Granta-519, As2O3 induced dose-dependent and time-dependent increases in apoptosis accompanied by cyclin D1 suppression. Downregulation of cyclin D1 resulted in decreased retinoblastoma protein phosphorylation, which led to repressed G1 progression to S/G2 phases. As2O3 did not affect cyclin D1 gene transcription. Instead, As2O3 activated glycogen synthase kinase-3beta (by tyrosine-216 phosphorylation) and IkappaB kinase alpha/beta (by serine-176/180 phosphorylation), both of which phosphorylated cyclin D1 at threonine-286, leading to its poly-ubiquitination and degradation in the proteasome. These observations were recapitulated partly in primary MCL samples obtained from patients refractory to conventional treatment. Our findings suggested that As2O3 might be clinically useful in MCL. PMID:23949314

  3. Arsenic trioxide rewires mantle cell lymphoma response to bortezomib

    PubMed Central

    Zhao, Ling-Ling; Liu, Yuan-Fang; Peng, Li-Jun; Fei, Ai-Mei; Cui, Wen; Miao, Sheng-Chao; Hermine, Olivier; Gressin, Remy; Khochbin, Saadi; Chen, Sai-Juan; Wang, Jin; Mi, Jian-Qing

    2015-01-01

    Although most of the mantle cell lymphoma (MCL) patients initially responded well to bortezomib (BTZ), the dose-dependent toxicities have greatly limited the application of BTZ to MCL. To investigate the efficacy and mechanism of arsenic trioxide (ATO) with BTZ in inducing apoptosis of MCL cells, two MCL cell lines, along with primary cells from MCL patients (n = 4), were used. Additionally, the NOD-SCID mice xenograft model of Jeko-1 cells was established to study the anti-MCL mechanisms in an in vivo setting. ATO treatment highly improved BTZ capacity to inhibit proliferation and induce apoptosis of MCL cells. Furthermore, the interaction of Noxa and Mcl-1 leads Bak to release from Mcl-1 or from Bcl-xl, which could further activate Bak and Bax and then induce cell apoptosis. We also found that when lower doses of BTZ were used in combination with ATO, more effective proapoptotic effects in both the cell lines and the primary cells were obtained compared to the effects of BTZ used alone at higher doses. Simultaneously, the combination of these two drugs delayed the tumor growth in mice more effectively than BTZ alone. The cooperative anti-MCL effects of this combination therapy both in vitro and in vivo strongly provided a new strategy to the clinical treatment of MCL. PMID:26310857

  4. Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

    SciTech Connect

    Ning Shoucheng; Knox, Susan J. . E-mail: sknox@stanford.edu

    2006-06-01

    Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5 days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.

  5. Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study

    PubMed Central

    Savlı, Hakan; Galimberti, Sara; Sünnetçi, Deniz; Canestraro, Martina; Palumbo, Giuseppe; Nagy, Balint; Raimondo, Francesco Di; Petrini, Mario

    2015-01-01

    Objective: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39. Materials and Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR. Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings. Conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS. PMID:25913414

  6. Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies.

    PubMed

    Tsai, Min-Ling; Yen, Cheng-Chieh; Lu, Fung-Jou; Ting, Hung-Chih; Chang, Horng-Rong

    2016-09-01

    In a previous study, treatment at higher concentrations of arsenic trioxide or co-exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis-related protein (MMP-2, MMP-9, and VEGF-A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co-exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound-healing activities, migration abilities, and MMP-2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug-treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP-2, MMP-9, and VEGF-A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121-1132, 2016. PMID:25728215

  7. Downregulation of B7-H4 in the MHCC97-H hepatocellular carcinoma cell line by arsenic trioxide

    PubMed Central

    CUI, LIMING; GAO, BO; CAO, ZHIGANG; CHEN, XIAOYING; ZHANG, SHIDE; ZHANG, WEIZHE

    2016-01-01

    Arsenic trioxide (As2O3; ATO), a compound which is characterized by its ability to function as a potent anticancer agent, has been investigated in a variety of carcinomas. B7-H4, a transmembrane protein, may inhibit the function of the T cell effector, and therefore, may be useful in investigating different types of tumor therapies. However, few studies have been published previously associated with the roles of ATO and B7-H4 in human hepatocellular carcinoma (HCC). The aim of the present study was to investigate the anti-invasive role of ATO in HCC, to determine the effect of ATO treatment on the expression of B7-H4 and to further assess the possible underlying mechanisms. Following treatment of the cells with 2, 4 and 8 µM ATO for 48 h, cell counting kit-8 (CCK-8), Transwell and western blot assays were used to determine the extent of human MHCC97-H HCC cell proliferation, apoptosis, invasion and B7-H4 expression, respectively. The results revealed that 1 µM ATO markedly decreased cellular proliferation, and ATO administered at concentrations of 0.1, 0.2 and 0.5 µM markedly inhibited the migration and invasion of the human MHCC97-H HCC cell line. The expression of B7-H4 in the treatment groups was markedly reduced. Signal transduction mediated via the Janus kinase 2/signal transducers and activators of transcription 3 pathway was inhibited upon treatment with 0.1, 0.2 and 0.5 µM ATO. Additionally, the protein expression levels of matrix metalloproteinase 2 and vascular endothelial growth factor were markedly reduced in HCC cells upon treatment with ATO. In conclusion, ATO may reduce the protein expression levels of B7-H4 in MHCC97-H HCC cells, and further affected HCC tumorigenesis and progression. ATO may be a putative agent for the development of therapeutic strategies against human liver cancer. PMID:26781180

  8. Antitumor efficacy of DMSA modified Fe3O4 magnetic nanoparticles combined with arsenic trioxide and adriamycin in Raji cells.

    PubMed

    Cai, Xiaohui; Cai, Xiaohui; Wang, Chunling; Chen, Baoan; Hua, Weijun; Shen, Fei; Yu, Liang; He, Zhengmei; Shi, Yuye; Chen, Yue; Xia, Guohua; Bao, Wen; Zhang, Yu; Wang, Xuemei

    2014-02-01

    The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Raji cells by the combined form of ADM and As2O3 was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM-As2O3, MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells would be a promising

  9. Effects of freshwater exposure to arsenic trioxide on the parr-smolt transformation of coho salmon (Oncorhynchus kisutch)

    USGS Publications Warehouse

    Nichols, J.W.; Wedemeyer, G.A.; Mayer, F.L.; Dickhoff, Walton W.; Gregory, S.V.; Yasutake, W.T.; Smith, S.D.

    1984-01-01

    The effects of chronic (6 months) exposure to arsenic trioxide in fresh water on the Parr-smolt transformation of coho salmon (Oncorhynchus kisutch) were evaluated. Exposure to 300 μg As/L (as As2O3) appeared to delay the onset of the normal increase in plasma thyroxine concentration and cause a transient reduction of gill Na+,K+-ATPase activity. Fish exposed to 300 μg As/L also migrated to the sea less successfully than did nonexposed smolts, but there were no effects on the survival and growth of smolts held in 28‰ salt water for 6 months.

  10. Arsenic trioxide inhibits tumor cell growth in malignant rhabdoid tumors in vitro and in vivo by targeting overexpressed Gli1.

    PubMed

    Kerl, Kornelius; Moreno, Natalia; Holsten, Till; Ahlfeld, Julia; Mertins, Julius; Hotfilder, Marc; Kool, Marcel; Bartelheim, Kerstin; Schleicher, Sabine; Handgretinger, Rupert; Schüller, Ulrich; Meisterernst, Michael; Frühwald, Michael C

    2014-08-15

    Rhabdoid tumors are highly aggressive tumors occurring in infants and very young children. Despite multimodal and intensive therapy prognosis remains poor. Molecular analyses have uncovered several deregulated pathways, among them the CDK4/6-Rb-, the WNT- and the Sonic hedgehog (SHH) pathways. The SHH pathway is activated in rhabdoid tumors by GLI1 overexpression. Here, we demonstrate that arsenic trioxide (ATO) inhibits tumor cell growth of malignant rhabdoid tumors in vitro and in a mouse xenograft model by suppressing Gli1. Our data uncover ATO as a promising therapeutic approach to improve prognosis for rhabdoid tumor patients. PMID:24420698

  11. Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.

    PubMed

    Yan, S; Zhang, Q Y; Zhou, B; Xue, L; Chen, H; Wang, Y; Zheng, S S

    2009-06-01

    We investigated the effects of arsenic trioxide (As(2)O(3)) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (1 mg/kg) from days -3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As(2)O(3)-treated group compared with the control group (17.2 +/- 1.9 vs 8.0 +/- 0.9 days; P < .05). A marked prolongation (28.6 +/- 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 +/- 3.0 days; P < .05) or the As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose. PMID:19545743

  12. Preferential action of arsenic trioxide in solid-tumor microenvironment enhances radiation therapy

    SciTech Connect

    Griffin, Robert J. . E-mail: griff007@umn.edu; Williams, Brent W.; Park, Heon Joo; Song, Chang W.

    2005-04-01

    Purpose: To investigate the effect of arsenic trioxide, Trisenox (TNX), on primary cultures of endothelial cells and tumor tissue under varying pH and pO{sub 2} environments and the effects of combined TNX and radiation therapy on experimental tumors. Methods and Materials: Human dermal microvascular endothelial cells were cultured in vitro and exposed to TNX under various combinations of aerobic, hypoxic, neutral, or acidic conditions, and levels of activated JNK MAP kinase were assessed by Western blotting. FSaII fibrosarcoma cells grown in the hind limb of female C3H mice were used to study the effect of TNX on tumor blood perfusion and oxygenation. The tumor-growth delay after a single or fractionated irradiation with or without TNX treatment was assessed. Results: A single intraperitoneal injection of 8 mg/kg TNX reduced the blood perfusion in FSaII tumors by 53% at 2 hours after injection. To increase the oxygenation of the tumor vasculature during TNX treatment, some animals were allowed to breathe carbogen (95% O{sub 2}/5% CO{sub 2}). Carbogen breathing alone for 2 hours reduced tumor perfusion by 33%. When carbogen breathing was begun immediately after TNX injection, no further reduction occurred in tumor blood perfusion at 2 hours after injection. In vitro, TNX exposure increased activity JNK MAP kinase preferentially in endothelial cells cultured in an acidic or hypoxic environment. In vivo, the median oxygenation in FSaII tumors measured at 3 or 5 days after TNX injection was found to be significantly elevated compared with control tumors. Subsequently, radiation-induced tumor-growth delay was synergistically increased when radiation and TNX injection were fractionated at 3-day or 5-day intervals. Conclusions: Trisenox has novel vascular-damaging properties, preferentially against endothelium in regions of low pH or pO{sub 2}, which leads to tumor cell death and enhancement of the response of tumors to radiotherapy.

  13. Effect of arsenic trioxide on different cell lines derived from chronic myeloid leukemia.

    PubMed

    Jing, Hong-Mei; Yukihiro, Shimizu; Ke, Xiao-Yan; Yoshiro, Kashii; Akiharu, Watanabe

    2002-10-01

    The objective is to explore the effect and the mechanism of arsenic trioxide, As(2)O(3), on different cell lines of chronic myeloid leukemia (CML). Different concentrations of As(2)O(3) (0.2, 2 and 10 micro mol/L) were added to CML cell lines KU812 and MEG-01 and other leukemia cell lines U937 and PL21, the cell numbers were counted at different times, TUNEL and DNA ladder were assayed. Different antibodies, CD34, CD13, CD33, CD19, CD11b, CD14 and CD7, were added to detect the change of the molecules on cell surface, the change of bcr-abl by RT-PCR and the activity of caspase-3 were assayed. The results showed that different concentrations of As(2)O(3) had different effects on the survival of the 4 cell lines. After culture for 24 hours with As(2)O(3), there was no significant increase in CD11b in all the four cell lines. There were no changes of bcr-abl in the two CML cell lines treated and untreated with As(2)O(3) by RT-PCR. Activities of caspase-3 were all increased. It is concluded that As(2)O(3) can induce apoptosis in CML cell lines, the concentration to induce apoptosis is different, CML cell lines are more sensitive than the other 2 leukemia cell lines. As(2)O(3) induced apoptosis may have some relation with the activation of caspase-3. PMID:12513739

  14. E2F1 downregulation by arsenic trioxide in lung adenocarcinoma.

    PubMed

    Lam, Sze-Kwan; Li, Yuan-Yuan; Zheng, Chun-Yan; Leung, Leanne Lee; Ho, James Chung-Man

    2014-11-01

    Lung cancer is one of the most common cancers worldwide. Arsenic trioxide (ATO) has been approved by the US Food and Drug Administration for the treatment of acute promyelocytic leukemia. Nonetheless preliminary data have suggested potential activity of ATO in solid tumors including lung cancer. This study aimed to examine the underlying mechanisms of ATO in the treatment of lung adenocarcinoma. Using a panel of 7 lung adenocarcinoma cell lines, the effects of ATO treatment on cell viability, expression of E2F1 and its downstream targets, phosphatidylserine externalization, mitochondrial membrane depolarization and alteration of apoptotic/anti-apoptotic factors were studied. Tumor growth inhibition in vivo was investigated using a nude mouse xenograft model. ATO decreased cell viability with clinically achievable concentrations (8 µM) in all cell lines investigated. This was accompanied by reduced expression of E2F1, cyclin A2, skp2, c-myc, thymidine kinase and ribonucleotide reductase M1, while p-c-Jun was upregulated. Cell viability was significantly decreased with E2F1 knockdown. Treatment with ATO resulted in phosphatidylserine externalization in H23 cells and mitochondrial membrane depolarization in all cell lines, associated with truncation of Bid, downregulation of Bcl-2, upregulation of Bax and Bak, caspase-9 and -3 activation and PARP cleavage. Using the H358 xenograft model, the tumor growth was suppressed in the ATO treatment group during 8 days of treatment, associated with downregulation of E2F1 and upregulation of truncated Bid and cleaved caspase-3. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, partially mediated through E2F1 downregulation and apoptosis. PMID:25174355

  15. Vitamin D3 potentiates the antitumorigenic effects of arsenic trioxide in human leukemia (HL-60) cells

    PubMed Central

    2014-01-01

    Background Arsenic trioxide (ATO) is a novel form of therapy that has been found to aid acute promyelocytic leukemia (APL) patients. Our laboratory has demonstrated that ATO-induced cytotoxicity in human leukemia (HL-60) cells is mediated by oxidative stress. Pro-oxidants have been known to play a role in free radical-mediated oxidative stress. Vitamin D3, (Vit D3) an active metabolite of vitamin D has been reported to inhibit the growth of number neoplasms such as prostate, breast, colorectal, leukemia, and skin cancers. The goal of the present research was to use (HL-60) cells as an in vitro test model to evaluate whether low doses of Vit D3 potentiate the toxicity of ATO and whether this toxic action is mediated via apoptotic mechanisms. Method HL-60 cells were treated either with a pharmacologic dose of ATO alone and with several low doses of Vit D3. Cell survival was determined by MTT assay. Cell apoptosis was measured both by flow cytometry assessment, and DNA laddering assay. Results MTT assay indicated that Vit D3 co-treatment potentiates ATO toxicity in HL-60 cells in a dose dependent manner. A statistically significant and dose-dependent increase (p <0.05) was recorded in annexin V positive cells (apoptotic cells) with increasing doses of Vit D3 in ATO-treated cells. This finding was confirmed by the result of DNA laddering assay showing clear evidence of nucleosomal DNA fragmentation in vitamin and ATO co-treated cells. Conclusion The present study indicates that Vit D3 potentiates the antitumor effects of ATO. This potentiation is mediated at least in part, through induction of phosphatidylserine externalization and nucleosomal DNA fragmentation. These findings highlight the potential impact of Vit D3 in promoting the pharmacological effect of ATO, suggesting a possible future role of Vit D3/ATO combination therapy in patients with acute promyelocytic leukemia (APL). PMID:24661615

  16. Heat Shock Protein Alteration in the Gastrointestinal Tract Tissues of Chickens Exposed to Arsenic Trioxide.

    PubMed

    Zhao, Panpan; Zhang, Kexin; Guo, Guangyang; Sun, Xiao; Chai, Hongliang; Zhang, Wen; Xing, Mingwei

    2016-03-01

    Arsenic (As) is widely distributed in our living environment and is useful for industry, agriculture, medical treatment, and other fields. Arsenic trioxide (As2O3) is an existing form of As. Exposure to As2O3 has a toxic effect on humans and animals. It not only leads to skin cancer, peripheral vascular disease, hyperkeratosis, etc. but also interferes with the functioning of the gastrointestinal tract. The gastrointestinal tract is an important organ for animals to transform the food they eat into the nutrients their body needs for maintenance and growth. Heat shock proteins (Hsps) exist in the non-stress normal cells and their expression increases under stimuli. Therefore, we wonder whether the "stimulus" of As2O3 could change the messenger RNA (mRNA) abundance and expression level of Hsps in the gastrointestinal tract of birds. To investigate the relation between arseniasis and Hsp alterations in the chicken's gastrointestinal tract induced by an As2O3-supplemented diet, we selected 72 one-day-old male Hy-line chickens and randomly divided them into four groups. They were fed either a commercial diet or an As2O3-supplemented 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. The mRNA contents of Hsps (including Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90) were examined by real-time PCR (RT-PCR). The correlation between As2O3 and Hsp genes was assessed. In addition, the protein expression levels of Hsp60 and Hsp70 in the gastrointestinal tract tissue samples were measured by western blot. The results indicated that the mRNA expression levels and the Hsp expression levels in the gastrointestinal tract tissues of chickens with As2O3 supplementation increased at different time points in a dose-dependent manner (p < 0.05 or p < 0.01). These data suggested that arseniasis influenced the

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

    NASA Astrophysics Data System (ADS)

    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. Arsenic Trioxide Attenuates NF-κB and Cytokine mRNA Levels in the Livers of Cocks.

    PubMed

    Zhang, Kexin; Zhao, Panpan; Guo, Guangyang; Guo, Ying; Tian, Li; Sun, Xiao; Li, Siwen; He, Ying; Sun, Ying; Chai, Hongliang; Zhang, Wen; Xing, Mingwei

    2016-04-01

    Arsenic (As) is a trace element widely found in nature. It exists in several forms, including organic arsenic, inorganic arsenic, and trivalent arsenic, the most toxic. Arsenic trioxide (As2O3) is widespread in nature. This form tends to accumulate in animals and humans and therefore has a potential harm for them. Cytokines play essential roles in the immune response and inflammation. Although the importance of cytokines in the responses to arsenic exposure has been demonstrated in many types of mammals, the function of these in poultry, especially in chickens, remains unclear. The purpose of the present study was to examine the effect of As2O3 exposure on cytokines in cock livers. In this study, 72 1-day-old male Hy-line cocks were randomly divided into four groups including the control group, low-As group, middle-As group, and high-As group. The livers were collected on days 30, 60, and 90 of the experiment. The levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 beta (IL-12β), and interleukin-1 beta (IL-1β) mRNA in the livers of the cocks were measured using real-time PCR. The results showed that the expression levels of IL-6, IL-8, TNF-α, and NF-κB which seemed to be a critical mediator in the inflammatory response tended to increase in the birds chronically treated with As2O3. However, the mRNA expression levels of IL-4, IL-12β, and IL-1β were decreased in the experiment. The information regarding the effects of As2O3 on cytokine mRNA expression generated in this study will be important information for arsenic toxicology evaluation. PMID:26276563

  19. (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

    PubMed

    dos Santos, G A S; Abreu e Lima, R S; Pestana, C R; Lima, A S G; Scheucher, P S; Thomé, C H; Gimenes-Teixeira, H L; Santana-Lemos, B A A; Lucena-Araujo, A R; Rodrigues, F P; Nasr, R; Uyemura, S A; Falcão, R P; de Thé, H; Pandolfi, P P; Curti, C; Rego, E M

    2012-03-01

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. PMID:21869839

  20. Have all-trans retinoic acid and arsenic trioxide replaced all-trans retinoic acid and anthracyclines in APL as standard of care.

    PubMed

    Iland, Harry J; Wei, Andrew; Seymour, John F

    2014-03-01

    Until recently, the standard of care in the treatment of APL has involved the combination of all-trans retinoic acid with anthracycline-based chemotherapy during both induction and consolidation. Additionally, the intensity of consolidation chemotherapy has evolved according to a universally accepted relapse-risk stratification algorithm based on the white cell and platelet counts at presentation. That standard of care is being challenged by the increasing incorporation of arsenic trioxide into front-line treatment protocols, based on two complementary observations. The first is the undoubted anti-leukaemic activity of arsenic trioxide as shown in the relapsed and refractory setting, and in the initial management of low- and intermediate-risk patients. The second is an improved understanding of the action of both all-trans retinoic acid and arsenic trioxide in mediating APL cell eradication, with increasing recognition that PML-RARA fusion protein degradation rather than direct induction of terminal differentiation is the primary mechanism for their ability to eliminate leukaemia initiating cells. As a result, we believe the standard of care for initial therapy in APL is shifting towards an all-trans retinoic acid plus arsenic trioxide-based approach, with additional chemotherapy reserved for patients with high-risk disease. PMID:24907016

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

    PubMed

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

    2016-02-21

    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. PMID:26840759

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

    PubMed Central

    Zhang, Ye; Wu, SiJing; Luo, Dan; Zhou, JianFeng; Li, DengJu

    2016-01-01

    Aim 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. Methods 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. Results 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). Conclusions Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who

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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed Central

    Kojima, Minoru; Ogiya, Daisuke; Ichiki, Akifumi; Hara, Ryujiro; Amaki, Jun; Kawai, Hidetsugu; Numata, Hiroki; Sato, Ai; Miyamoto, Mitsuki; Suzuki, Rikio; Machida, Shinichiro; Matsushita, Hiromichi; Ogawa, Yoshiaki; Kawada, Hiroshi; Ando, Kiyoshi

    2016-01-01

    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 As2O3as a single agent. PMID:27144119

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

    PubMed

    Kojima, Minoru; Ogiya, Daisuke; Ichiki, Akifumi; Hara, Ryujiro; Amaki, Jun; Kawai, Hidetsugu; Numata, Hiroki; Sato, Ai; Miyamoto, Mitsuki; Suzuki, Rikio; Machida, Shinichiro; Matsushita, Hiromichi; Ogawa, Yoshiaki; Kawada, Hiroshi; Ando, Kiyoshi

    2016-01-01

    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. PMID:27144119

  6. Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML.

    PubMed

    Weisshaar, Stefan R; Keusekotten, Kirstin; Krause, Anke; Horst, Christiane; Springer, Helen M; Göttsche, Kerstin; Dohmen, R Jürgen; Praefcke, Gerrit J K

    2008-09-22

    We have recently reported that poly-SUMO-2/3 conjugates are subject to a ubiquitin-dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO-2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. The SUMO-binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Reconstitution of SUMO-dependent ubiquitylation of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4. PMID:18708055

  7. IMMUNOTOXICITY AND BIODISTRIBUTION ANALYSIS OF ARSENIC TRIOXIDE IN C57Bl/6 MICE FOLLOWING A TWO-WEEK INHALATION EXPOSURE

    PubMed Central

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun, Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu, Ke Jian

    2010-01-01

    In these studies the immunotoxicity of arsenic trioxide (ATO, As2O3) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 hrs per day) at concentrations of 50 μg/m3 and 1 mg/m3. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 μg/mg tissue following the 1 mg/m3 exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 μg/m3 and 1 mg/m3 exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents. PMID:19800901

  8. Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

    SciTech Connect

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

    2009-12-15

    In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 3}. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 mug/g tissue following the 1 mg/m{sup 3} exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 mug/m{sup 3} and 1 mg/m{sup 3} exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

  9. Alterations in Glutathione Levels and Apoptotic Regulators Are Associated with Acquisition of Arsenic Trioxide Resistance in Multiple Myeloma

    PubMed Central

    Yehiayan, Lucy; Lee, Kelvin P.; Cai, Yong; Boise, Lawrence H.

    2012-01-01

    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. PMID:23285138

  10. Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells.

    PubMed

    Zeng, Yingjian; Weng, Guangyang; Fan, Jiaxin; Li, Zhangqiu; Wu, Jianwei; Li, Yuanming; Zheng, Rong; Xia, Pingfang; Guo, Kunyuan

    2016-09-01

    Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre‑LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin. PMID:27430728

  11. Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells

    PubMed Central

    Zeng, Yingjian; Weng, Guangyang; Fan, Jiaxin; Li, Zhangqiu; Wu, Jianwei; Li, Yuanming; Zheng, Rong; Xia, Pingfang; Guo, Kunyuan

    2016-01-01

    Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre-LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin. PMID:27430728

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide.

    PubMed

    Liu, Liu; Chen, Chen; Gong, Wei; Li, Yuanjing; Edin, Matthew L; Zeldin, Darryl C; Wang, Dao Wen

    2011-11-01

    Epoxyeicosatrienoic acids (EETs) and the cytochrome P450 epoxygenase CYP2J2 promote tumorogenesis in vivo and in vitro via direct stimulation of tumor cell growth and inhibition of tumor cell apoptosis. Herein, we describe a novel mechanism of inhibition of tumor cell apoptosis by EETs. In Tca-8113 cancer cells, the antileukemia drug arsenic trioxide (ATO) led to the generation of reactive oxygen species (ROS), impaired mitochondrial function, and induced apoptosis. 11,12-EET pretreatment increased expression of the antioxidant enzymes superoxide dismutase and catalase and inhibited ATO-induced apoptosis. 11,12-EET also prevented the ATO-induced activation of p38 mitogen-activated protein kinase, c-Jun NH(2)-terminal kinase, caspase-3, and caspase-9. Therefore, 11,12-EET-pretreatment attenuated the ROS generation, loss of mitochondrial function, and caspase activation observed after ATO treatment. Moreover, the CYP2J2-specific inhibitor compound 26 enhanced arsenic cytotoxicity to a clinically relevant concentration of ATO (1-2 μM). Both the thiol-containing antioxidant, N-acetyl-cysteine, and 11,12-EET reversed the synergistic effect of the two agents. Taken together, these data indicate that 11,12-EET inhibits apoptosis induced by ATO through a mechanism that involves induction of antioxidant proteins and attenuation of ROS-mediated mitochondrial dysfunction. PMID:21846841

  14. BIBR 1532 increases arsenic trioxide-mediated apoptosis in acute promyelocytic leukemia cells: therapeutic potential for APL.

    PubMed

    Bashash, Davood; Ghaffari, Seyed H; Zaker, Farhad; Kazerani, Maryam; Hezave, Kebria; Hassani, Saeed; Rostami, Masomeh; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2013-09-01

    The current treatment of acute promyelocytic leukemia with arsenic trioxide (ATO) has increased long-lasting complete remissions; however, a proportion of patients continues to die eventually as a result of disease recurrence. In an effort to enhance the effectiveness of the APL treatment, we designed experiments to evaluate the effects of ATO in combination with the lead compound of non-nucleoside inhibitor of telomerase, BIBR 1532. After combined treatments with BIBR 1532 and ATO, decreased cell viability index with a concomitant increase in apoptotic cell death was observed in NB4 leukemic cells. Apoptosis induced by the combined treatments was accompanied by elevated Bax/Bcl-2 molecular ratio and enhanced caspase 3 activation. Our study has also demonstrated that the combined treatment suppressed NB4 cell proliferative capacity and inhibited telomerase activity probably via transcriptional suppression of c-Myc and hTERT. In conclusion, this study may supply insight into the application of this new combination therapy to APL cells intrinsically less sensitive to routine therapies and suggested a novel combination therapy for patients with more aggressive disease; those who may not respond favorably to the arsenic mono-therapy. PMID:23293885

  15. Outcome of Therapy-Related Acute Promyelocytic Leukemia With or Without Arsenic Trioxide as a Component of Frontline Therapy

    PubMed Central

    Dayyani, Farshid; Kantarjian, Hagop; O’Brien, Susan; Pierce, Sherry; Jones, Dan; Faderl, Stefan; Garcia-Manero, Guillermo; Cortes, Jorge; Ravandi, Farhad

    2015-01-01

    BACKGROUND Patients with therapy-related acute promyelocytic leukemia (t-APL) have been commonly exposed to topoisomerase inhibitors and may potentially benefit from induction regimens omitting anthracyclines. METHODS Retrospective analysis of the outcomes of 29 patients with t-APL who were either treated with arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) or with standard ATRA plus anthracycline-based chemotherapy was performed. RESULTS Prior therapy included chemotherapy alone, radiation alone, or a combination of the 2 in 19%, 33%, and 47% of patients, respectively. The combination of ATO and ATRA (n = 19) for induction resulted in a similar remission rate compared with ATRA plus chemotherapy (n = 10) (89% vs 70%; P = .35). The median overall survival for the patients treated with ATRA plus ATO was not reached compared with that for patients treated with ATRA plus chemotherapy (161 weeks; P =.79). CONCLUSIONS In this cohort of t-APL patients, outcomes with ATO and ATRA appeared to be comparable to anthracycline-containing induction regimens. This combination may be preferable in t-APL patients to avoid any risk of anthracycline-induced toxicities. PMID:20803607

  16. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line.

    PubMed

    Meng, Ran; Zhou, Jin; Sui, Meng; Li, ZhiYong; Feng, GuoSheng; Yang, BaoFeng

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) 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 As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-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 As(2)O(3) 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 As(2)O(3) in APL treatment. PMID:20596959

  17. Arsenic Trioxide Activate Transcription of Heme Oxygenase-1 by Promoting Nuclear Translocation of NFE2L2

    PubMed Central

    Yue, Zhen; Zhong, Lingzhi; Mou, Yan; Wang, Xiaotong; Zhang, Haiying; Wang, Yang; Xia, Jianxin; Li, Ronggui; Wang, Zonggui

    2015-01-01

    In a previous study, we found that induced expression of Heme Oxygenase-1 (HO-1) is responsible for the resistance of human osteosarcoma MG63 cells to the chemotherapeutic agent arsenic trioxide (ATO). The present study was aimed at investigating the molecular mechanisms underlying the induction of HO-1 that occurs after exposure of MG63 cells to ATO. First, using RT-QPCT and Western-blot, we found that ATO strongly induced the expression of heme oxygenase-1 (HO-1) in these human osteosarcoma cells. Then by analyzing HO-1 mRNA of MG63 cells exposed to ATO in the presence and absence of a transcription inhibitor Actinomycin-D (Act-D), we demonstrated that ATO activates HO-1 expression in MG63 cells by regulating the transcription of the gene. Finally, through the analysis of the NFE2L2 protein levels among the total cellular and nuclear proteins by Western-blot and Immunocytochemical staning, we determined that ATO enhanced the nuclear translocation of nuclear factor erythroid 2-like 2 (NFE2L2), also known as Nrf2. From these results we have concluded that transcription activation of HO-1 resulting from the nuclear translocation of NFE2L2 is the underlying molecular mechanism for its high induction, which, in turn, is responsible for the resistance of human osteosarcoma cells to ATO treatment. PMID:26283888

  18. The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System

    PubMed Central

    da Silva, Raquel Frenedoso; Borges, Cibele dos Santos; Villela e Silva, Patrícia; Kiguti, Luiz Ricardo Almeida; Pupo, André Sampaio; Barbosa Junior, Fernando; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2016-01-01

    Arsenic trioxide (As2O3) has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N-acetylcysteine (NAC) may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system. PMID:26839632

  19. [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on RPMI 8226 cells and its mechanism].

    PubMed

    Wang, Xiao-Ning; Zhang, Mei

    2014-08-01

    This study was aimed to investigate the apoptosis-inducing effect of valproic acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI 8226 cells and its mechanism. The cell proliferation of RPMI 8226 cells was assayed by CCK-8 method. The cell apoptosis were detected by flow cytometry. Semiquantitative RT-PCR and Western blot were applied respectively to detect the mRNA and protein expression level of BCL-2, BAX, caspase-8 and caspase-9 gene. The results showed that both the VPA and ATO inhibited RPMI 8226 cell proliferation. The combination of ATO and VPA has synergistic effect (Q values greater than 1.15). The RPMI 8226 cell apoptosis rate in combined drug group was significantly higher than that in single drug group (P < 0.05). The mRNA and protein expressions of BCL-2 gene in combined drug group decreased, while the mRNA and protein expressions of BAX, caspase-8 and caspase-9 significantly increased, compared with single drug group (P < 0.05) . It is concluded that VPA can enhance the sensitivity of RPMI 8226 cells to ATO-induced apoptosis, which may be associated with decreasing the BCL-2 expression and increasing the BAX, caspase-8 and caspase-9 gene expression. PMID:25130820

  20. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet.

    PubMed

    Lengfelder, E; Lo-Coco, F; Ades, L; Montesinos, P; Grimwade, D; Kishore, B; Ramadan, S M; Pagoni, M; Breccia, M; Huerta, A J G; Nloga, A M; González-Sanmiguel, J D; Schmidt, A; Lambert, J-F; Lehmann, S; Di Bona, E; Cassinat, B; Hofmann, W-K; Görlich, D; Sauerland, M-C; Fenaux, P; Sanz, M

    2015-05-01

    In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively. PMID:25627637

  1. Arsenic trioxide enhances the cytotoxic effect of cisplatin in head and neck squamous cell carcinoma cell lines

    PubMed Central

    KOTOWSKI, ULANA; HEIDUSCHKA, GREGOR; BRUNNER, MARKUS; EROVIC, BOBAN M.; MARTINEK, HELGA; THURNHER, DIETMAR

    2012-01-01

    Arsenic trioxide (ATO) has been approved for the treatment of relapsed acute promyelocytic leukaemia. The aim of this study was to determine whether ATO would lead to cell death in head and neck squamous cell carcinoma (HNSCC) cell lines and whether it was able to enhance the cytotoxicity of cisplatin, a standard chemotherapeutic agent. The four HNSCC cell lines SCC9, SCC25, CAL27 and FADU were treated with ATO or cisplatin alone or with ATO and cisplatin in combination. Cytotoxicity assays, immunohistochemistry, western blot analysis and flow cytometry were carried out. Possible interactions between the two drugs were calculated using the Chou-Talalay equation. Ther results demonstrated a synergistic cytotoxic effect of the combination of ATO and cisplatin at high doses. The two agents induced apoptosis in all four HNSCC cell lines. In conclusion, this study showed that ATO is a promising therapeutic drug with cytotoxic effects in HNSCC. We demonstrated a synergistic effect in the combined treatment with cisplatin at high doses. PMID:22783443

  2. Consolidation therapy of arsenic trioxide alternated with chemotherapy achieves remarkable efficacy in newly diagnosed acute promyelocytic leukemia

    PubMed Central

    Liu, Cheng-cheng; Wang, Hua; Wang, Wei-da; Zhu, Meng-yuan; Geng, Qi-rong; Lu, Yue

    2015-01-01

    Background Currently, all-trans retinoic acid (ATRA) combined with daunorubicin and ATRA combined with arsenic trioxide (ATO) therapies are considered the standard induction therapy regimens for adult patients newly diagnosed with acute promyelocytic leukemia (APL). However, there is no consensus concerning the optimal consolidation and maintenance therapies after induction therapy. In this study, we explored a new therapeutic strategy for APL that may be simple, effective, and safe. Methods The patients in our study were divided into high white blood cell (WBC) group and low WBC group according to the numeration of leukocytes at the first visit. The low WBC group received ATRA and ATO until complete remission (CR), and the high WBC group received anthracycline, ATRA, and ATO until CR. After achieving hematologic CR, ATO was alternated with chemotherapy for consolidation therapy. Three cycles were completed in the 1st year with no maintenance therapy. The patients were followed for a median of 5 years after their initial treatment. Results After induction therapy, the rate of CR for the 18 patients was 100%. The rate of negativity for the PML/RARα fusion gene following induction therapy was 100%. There was no mortality during the treatment. Both the 5-year event-free survival rate and 5-year overall survival rate were 100%. No relapses occurred during the follow-up period. Conclusion This study proposes a novel treatment for APL that is efficient, well-tolerated, and very simple to perform. PMID:26622182

  3. Perturbation of cellular oxidative state induced by dichloroacetate and arsenic trioxide for treatment of acute myeloid leukemia.

    PubMed

    Emadi, Ashkan; Sadowska, Mariola; Carter-Cooper, Brandon; Bhatnagar, Vishal; van der Merwe, Isabella; Levis, Mark J; Sausville, Edward A; Lapidus, Rena G

    2015-07-01

    The incidence of acute myeloid leukemia (AML) is rising and the outcome of current therapy, which has not changed significantly in the last 40 years, is suboptimal. Cellular oxidative state is a credible target to selectively eradicate AML cells, because it is a fundamental property of each cell that is sufficiently different between leukemic and normal cells, yet its aberrancy shared among different AML cells. To this end, we tested whether a short-time treatment of AML cells, including cells with FLT3-ITD mutation, with sub-lethal dose of dichloroacetate (DCA) (priming) followed by pharmacologic dose of arsenic trioxide (ATO) in presence of low-dose DCA could produce insurmountable level of oxidative damage that kill AML cells. Using cellular cytotoxicity, apoptotic and metabolic assays with both established AML cell lines and primary AML cells, we found that priming with DCA significantly potentiated the cytotoxicity of ATO in AML cells in a synergistic manner. The combination decreased the mitochondrial membrane potential as well as expression of Mcl-1 and GPx in primary AML cells more than either drug alone. One patient with AML whose disease was refractory to several lines of prior treatments was treated with this combination, and tolerated it well. These data suggest that targeting cellular redox balance in leukemia may provide a therapeutic option for AML patients with relapsed/refractory disease. PMID:25982179

  4. VEGFA Expression Is Inhibited by Arsenic Trioxide in HUVECs through the Upregulation of Ets-2 and miRNA-126.

    PubMed

    Ge, Hong-Yan; Han, Zhong-Jing; Tian, Pei; Sun, Wen-Jie; Xue, Da-Xi; Bi, Yu; Yang, Zhang-Hui; Liu, Ping

    2015-01-01

    Arsenic trioxide (ATO) has been used to treat patients with acute promyelocytic leukemia. Recently, studies have shown that ATO can induce apoptosis in leukemic cells and blood vessel endothelial cells in a time- and dose-dependent manner through the inhibition of vascular endothelial growth factor A (VEGFA) production. VEGFA is a key factor in angiogenesis initiation. Targeted inhibition of VEGF or VEGFA expression can suppress angiogenesis; however, little is known about the mechanism by which ATO inhibits VEGFA expression. In this study, we investigated the role of miRNA-126 in the mechanism of action of ATO in human umbilical vein endothelial cells (HUVECs). ATO significantly decreased the viability and proliferation of HUVECs and decreased their migration at 48 h. Cell proliferation was inhibited by 50% (IC50) when 5.0 μmol/L ATO was used. ATO treatment induced miR-126 upregulation and HUVEC apoptosis. Transfection with a miR-126 mimic significantly downregulated VEGFA mRNA levels, and transfection with a miR-126 inhibitor significantly upregulated VEGFA mRNA levels. Finally, we showed that ATO treatment upregulated Ets-2 and miR-126 expression in HUVECs. These results demonstrate that ATO inhibits the growth of HUVECs and induces apoptosis by downregulating VEGFA. One mechanism by which this occurs is Ets-2 upregulation, which results in an increase in miR-126 levels and downregulation of VEGFA expression. PMID:26274316

  5. Cytotoxicity of arsenic trioxide is enhanced by (-)-epigallocatechin-3-gallate via suppression of ferritin in cancer cells

    SciTech Connect

    Lee, Te-Chang; Cheng, I-Cheng; Shue, Jun-Jie; Wang, T.C.

    2011-01-01

    Arsenic trioxide (ATO) treatment is a useful therapy against human acute promyelocytic leukemia (APL), however, it concomitantly brings potential adverse consequences including serious side effect, human carcinogenicity and possible development of resistance. This investigation revealed that those problems might be relaxed by simultaneous application with (-)-epigallocatechin-3-gallate (EGCG), one of the major components from green tea. EGCG significantly lowered down the ATO concentration required for an effective control of APL cells, HL-60. The simultaneous treatment of ATO with EGCG induced a mitochondria-dependent apoptosis in HL-60 cells significantly, which accounted for more than 70% of the cell death in the treatment. The mechanism of apoptosis induction was elucidated. EGCG in HL-60 cells acted as a pro-oxidant enhancing intracellular hydrogen peroxide significantly. ATO, on the other hand, induced heme oxygenase-1 (HO-1) to catalyze heme degradation, thereby provided ferrous iron for EGCG-induced hydrogen peroxide to precede Fenton reaction, which in turn generated deleterious reactive oxygen species to damage cell. In addition, EGCG inhibited expression of ferritin, which supposedly to sequester harmful ferrous iron, thereby augmented the occurrence of Fenton reaction. This investigation also provided evidence that ATO, since mainly acted to induce HO-1 in simultaneous treatment with EGCG, could be replaced by other HO-1 inducer with much less human toxicity. Furthermore, several of our preliminary investigations revealed that the enhanced cytotoxicity induced by combining heme degradation and Fenton reaction is selectively toxic to malignant but not non-malignant cells.

  6. Arsenic trioxide-based therapy in relapsed/refractory multiple myeloma patients: a meta-analysis and systematic review.

    PubMed

    He, Xuepeng; Yang, Kai; Chen, Peng; Liu, Bing; Zhang, Yuan; Wang, Fang; Guo, Zhi; Liu, Xiaodong; Lou, Jinxing; Chen, Huiren

    2014-01-01

    Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting. PMID:25246802

  7. Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer

    PubMed Central

    Chang, Ke-Jie; Yang, Meng-Hang; Zheng, Jin-Cheng; Li, Bing; Nie, Wei

    2016-01-01

    Cancer stem cells (CSCs) are responsible for the tumorigenesis and recurrence, so targeting CSCs is a potential effective method to cure cancers. Activated Hedgehog signaling pathway has been proved to be implicated in the maintenance of self-renewal of CSCs, and arsenic trioxide (As2O3) has been reported to inhibit Gli1, a key transcription factor of Hedgehog pathway. In this study, we evaluated whether As2O3 has inhibitory effects on cancer stem-like cells (CSLCs) in lung cancer and further explored the possible mechanism. CCK8 assay and colony formation assay were performed to demonstrate the ability of As2O3 to inhibit the growth of NCI-H460 and NCI-H446 cells, which represented non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), respectively. Tumor sphere formation assay was carried out to evaluate the effects of As2O3 on stem cell-like subpopulations. The expression of stem cell biomarkers CD133 and stem cell transcription factors such as Sox2 and Oct4 were detected. Moreover, the effects of As2O3 on expression of Gli1 and its target genes were observed. We found that As2O3 inhibited the cell proliferation and reduced the colony formation ability. Importantly, As2O3 decreased the formation of tumor spheres. The expression of stem cell biomarker CD133 and stem cell transcription factors such as Sox2 and Oct4 were markedly reduced by As2O3 treatment. Furthermore, As2O3 decreased the expression of Gli1, N-myc and GAS1. Our results suggested that As2O3 is a promising agent to inhibit CSLCs in lung cancer. In addition, the mechanism of CSLCs inhibition might involve Gli1 down-regulation. PMID:27158399

  8. Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide.

    PubMed

    Sanford, David; Lo-Coco, Francesco; Sanz, Miguel A; Di Bona, Eros; Coutre, Steven; Altman, Jessica K; Wetzler, Meir; Allen, Steven L; Ravandi, Farhad; Kantarjian, Hagop; Cortes, Jorge E

    2015-11-01

    Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of complete cytogenetic response was 43% (n = 6) and the rate of complete molecular response was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a median of 4·6 months (range 1·6-26·8 months). The median event-free survival (EFS) was 3·5 months [95% confidence interval (CI) 0-8·6 months] and the median overall survival (OS) was 9·5 months (95% CI 5·9-13·1 months). These results demonstrate that tamibarotene has activity in relapsed APL after treatment with ATO and ATRA and further studies using tamibarotene as initial therapy and in combination with ATO are warranted. PMID:26205361

  9. Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model.

    PubMed

    Hao, Li; Ran, Wang; Xiang-Xin, Li; Lu-Qun, Wang; Xiao-Ning, Yu

    2016-09-01

    Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity. PMID:26998898

  10. Effective Treatment of Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin

    PubMed Central

    Ravandi, Farhad; Estey, Eli; Jones, Dan; Faderl, Stefan; O'Brien, Susan; Fiorentino, Jackie; Pierce, Sherry; Blamble, Deborah; Estrov, Zeev; Wierda, William; Ferrajoli, Alessandra; Verstovsek, Srdan; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop

    2009-01-01

    Purpose We examined the outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) with or without gemtuzumab ozogamicin (GO) but without traditional cytotoxic chemotherapy. Patients and Methods From February 2002 to March 2008, 82 patients with APL were treated with a combination of ATRA plus ATO. The first cohort of 65 patients received ATRA and ATO (beginning on day 10 of ATRA). High-risk patients (WBCs ≥ 10 × 109/L) received GO on the first day. From July 2007, the second cohort of 17 patients received ATRA and ATO concomitantly on day 1. They also received GO on day 1, if high risk, and if their WBC increased to more than 30 × 109/L during induction. Monitoring for PML-RARA fusion gene was conducted after induction and throughout consolidation and follow-up. Results Overall, 74 patients achieved complete remission (CR) and one achieved CR without full platelet recovery after the induction, for a response rate of 92%. Seven patients died at a median of 4 days (range, 1 to 24 days) after inclusion in the study from disease-related complications. The median follow-up is 99 weeks (range, 2 to 282 weeks). Among the responding patients, three experienced relapse at 39, 52, and 53 weeks. Three patients died after being in CR for 14, 21, and 71 weeks, all from a second malignancy. The estimated 3-year survival rate is 85%. Conclusion The combination of ATRA and ATO (with or without GO) as initial therapy for APL was effective and safe and can substitute chemotherapy-containing regimens. PMID:19075265

  11. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells

    PubMed Central

    2014-01-01

    Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted in complete remission. Recently published studies from our laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is associated with cytotoxic and genotoxic effects in leukemia cells. Methods In the present study, we further investigated the detailed molecular mechanism of ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model. Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH levels while genotoxicity was determined by single cell gel electrophoresis (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax, Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal imaging of Bax and Cyt c translocation and mitochondrial membrane potential depolarization. Results ATO significantly (p < 0.05) induces oxidative stress, DNA damage, and caspase 3 activityin HL-60 cells in a dose-dependent manner. It also activated the intrinsic pathway of apoptosis by significantly modulating (p < 0.05) the expression and translocation of apoptotic molecules and decreasing the mitochondrial membrane potential in leukemia cells. Conclusion Taken together, our research demonstrated that ATO induces mitochondrial pathway of apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative stress, DNA damage, and change in mitochondrial membrane potential, translocation and upregulation of apoptotic proteins leading programmed cell death. PMID:24887205

  12. Synergistic effects of valproic acid and arsenic trioxide on RPMI8226 cells in vitro and the possible underlying mechanisms.

    PubMed

    Wang, Xiaoning; Zhang, Mei

    2015-07-01

    The aim of the present study was to investigate the synergistic effects of valproic acid (VPA) and arsenic trioxide (ATO) on the proliferation of RPMI8226 cells and the possible underlying mechanisms. Cell apoptosis was assessed by flow cytometry. The mRNA expression levels were analyzed by semi-quantitative polymerase chain reaction, and the protein expression levels were analyzed by western blotting. The histone acetylation and methylation states of the gene promoters were detected using a chromatin immunoprecipitation technique. The apoptotic rates of the RPMI8226 cells in the combined drug groups were significantly increased compared with those of the single drug groups (P<0.05). The mRNA and protein expression levels of Bcl-2 and the expression levels of HDAC1 mRNA and H3K9me2 protein decreased significantly in the combined groups compared with the single drug groups. The mRNA and protein expression levels of Bax, Caspase 8, Caspase 9 and LSD1, and the protein expression of acetylated H3 increased significantly in the combination groups compared with the single drug groups. Histone methylation and acetylation of the Bcl-2 and bax gene promoters were increased in the combination groups compared with the single drug groups. VPA and ATO had synergistic effects on the proliferation of RPMI8226 cells, which may have been associated with the decreased expression of Bcl-2 and the increased expression levels of Bcl-2-associated X protein, Caspase 8 and Caspase 9. Therefore, the expression levels of the Bcl-2 gene family may have been regulated by the levels of gene promoter methylation and acetylation. PMID:25815518

  13. Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer.

    PubMed

    Chang, Ke-Jie; Yang, Meng-Hang; Zheng, Jin-Cheng; Li, Bing; Nie, Wei

    2016-01-01

    Cancer stem cells (CSCs) are responsible for the tumorigenesis and recurrence, so targeting CSCs is a potential effective method to cure cancers. Activated Hedgehog signaling pathway has been proved to be implicated in the maintenance of self-renewal of CSCs, and arsenic trioxide (As2O3) has been reported to inhibit Gli1, a key transcription factor of Hedgehog pathway. In this study, we evaluated whether As2O3 has inhibitory effects on cancer stem-like cells (CSLCs) in lung cancer and further explored the possible mechanism. CCK8 assay and colony formation assay were performed to demonstrate the ability of As2O3 to inhibit the growth of NCI-H460 and NCI-H446 cells, which represented non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), respectively. Tumor sphere formation assay was carried out to evaluate the effects of As2O3 on stem cell-like subpopulations. The expression of stem cell biomarkers CD133 and stem cell transcription factors such as Sox2 and Oct4 were detected. Moreover, the effects of As2O3 on expression of Gli1 and its target genes were observed. We found that As2O3 inhibited the cell proliferation and reduced the colony formation ability. Importantly, As2O3 decreased the formation of tumor spheres. The expression of stem cell biomarker CD133 and stem cell transcription factors such as Sox2 and Oct4 were markedly reduced by As2O3 treatment. Furthermore, As2O3 decreased the expression of Gli1, N-myc and GAS1. Our results suggested that As2O3 is a promising agent to inhibit CSLCs in lung cancer. In addition, the mechanism of CSLCs inhibition might involve Gli1 down-regulation. PMID:27158399

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

    SciTech Connect

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    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.

  15. Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms.

    PubMed

    Maroui, Mohamed Ali; Kheddache-Atmane, Sabrina; El Asmi, Faten; Dianoux, Laurent; Aubry, Muriel; Chelbi-Alix, Mounira K

    2012-01-01

    PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene. This variability is important for the function of the different PML isoforms. PML NB formation requires the covalent linkage of SUMO to PML. Arsenic trioxide (As₂O₃) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Furthermore, the presence of a bona fide SUMO Interacting Motif (SIM) within the C-terminal region of PML seems to be required for recruitment of other SUMOylated proteins within PML NBs. This motif is present in all PML isoforms, except in the nuclear PMLVI and in the cytoplasmic PMLVII. Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As₂O₃ enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI). In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As₂O₃-induced PML degradation. Similarly, mutation of the SIM in PMLIII abrogated its sensitivity to As₂O₃-induced degradation. PMLVI and PMLIII-SIM mutant still interacted with RNF4. However, their resistance to the degradation process was due to their inability to be polyubiquitinated and to recruit efficiently the 20S core and the β regulatory subunit of the 11S complex of the proteasome in PML NBs. Such resistance of PMLVI to As₂O₃-induced degradation was alleviated by overexpression of RNF4. Our results demonstrate that the SIM of PML is dispensable for PML SUMOylation and interaction with RNF4 but is required for efficient PML ubiquitination, recruitment of proteasome components within NBs and proteasome-dependent degradation of PML in response to As₂O₃. PMID:23028697

  16. pH-triggered sustained release of arsenic trioxide by polyacrylic acid capped mesoporous silica nanoparticles for solid tumor treatment in vitro and in vivo.

    PubMed

    Xiao, Xuecheng; Liu, Yangyang; Guo, Manman; Fei, Weidong; Zheng, Hongyue; Zhang, Rongrong; Zhang, Yan; Wei, Yinghui; Zheng, Guohua; Li, Fanzhu

    2016-07-01

    Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell in vitro or solid tumor in vivo. However, its effect on solid tumor in vivo was hampered by its poor pharmacokinetics and dose-limited toxicity. In this study, a polyacrylic acid capped pH-triggered mesoporous silica nanoparticles was conducted to improve the pharmacokinetics and enhance the antitumor effect of arsenic trioxide. The mesoporous silica nanoparticles loaded with arsenic trioxide was grafted with polyacrylic acid (PAA-ATO-MSN) as a pH-responsive biomaterial on the surface to achieve the release of drug in acidic microenvironment of tumor, instead of burst release action in circulation. The nanoparticles were characterized with uniform grain size (particle sizes of 158.6 ± 1.3 nm and pore sizes of 3.71 nm, respectively), historically comparable drug loading efficiency (11.42 ± 1.75%), pH-responsive and strengthened sustained release features. The cell toxicity of amino groups modified mesoporous silica nanoparticles (NH2-MSN) was significantly reduced by capping of polyacrylic acid. In pharmacokinetic studies, the half time (t1/2β) was prolonged by 1.3 times, and the area under curve) was increased by 2.6 times in PAA-ATO-MSN group compared with free arsenic trioxide group. Subsequently, the antitumor efficacy in vitro (SMMC-7721 cell line) and in vivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug. These results suggest that the polyacrylic acid capped mesoporous silica nanoparticles (PAA-MSN) will be a promising nanocarrier for improving pharmacokinetic features and enhancing the anti-tumor efficacy of arsenic trioxide. PMID:27059495

  17. Requirement of PML SUMO Interacting Motif for RNF4- or Arsenic Trioxide-Induced Degradation of Nuclear PML Isoforms

    PubMed Central

    El Asmi, Faten; Dianoux, Laurent; Aubry, Muriel; Chelbi-Alix, Mounira K.

    2012-01-01

    PML, the organizer of nuclear bodies (NBs), is expressed in several isoforms designated PMLI to VII which differ in their C-terminal region due to alternative splicing of a single gene. This variability is important for the function of the different PML isoforms. PML NB formation requires the covalent linkage of SUMO to PML. Arsenic trioxide (As2O3) enhances PML SUMOylation leading to an increase in PML NB size and promotes its interaction with RNF4, a poly-SUMO-dependent ubiquitin E3 ligase responsible for proteasome-mediated PML degradation. Furthermore, the presence of a bona fide SUMO Interacting Motif (SIM) within the C-terminal region of PML seems to be required for recruitment of other SUMOylated proteins within PML NBs. This motif is present in all PML isoforms, except in the nuclear PMLVI and in the cytoplasmic PMLVII. Using a bioluminescence resonance energy transfer (BRET) assay in living cells, we found that As2O3 enhanced the SUMOylation and interaction with RNF4 of nuclear PML isoforms (I to VI). In addition, among the nuclear PML isoforms, only the one lacking the SIM sequence, PMLVI, was resistant to As2O3-induced PML degradation. Similarly, mutation of the SIM in PMLIII abrogated its sensitivity to As2O3-induced degradation. PMLVI and PMLIII-SIM mutant still interacted with RNF4. However, their resistance to the degradation process was due to their inability to be polyubiquitinated and to recruit efficiently the 20S core and the β regulatory subunit of the 11S complex of the proteasome in PML NBs. Such resistance of PMLVI to As2O3-induced degradation was alleviated by overexpression of RNF4. Our results demonstrate that the SIM of PML is dispensable for PML SUMOylation and interaction with RNF4 but is required for efficient PML ubiquitination, recruitment of proteasome components within NBs and proteasome-dependent degradation of PML in response to As2O3. PMID:23028697

  18. Differential in vivo genotoxicity of arsenic trioxide in glutathione depleted mouse bone marrow cells: expressions of Nrf2/Keap1/P62.

    PubMed

    Srivastava, Ritu; Bhattacharya, Shelley; Chakraborty, Anindita; Chattopadhyay, Ansuman

    2015-03-01

    Generation of reactive oxygen species is one of the major contributors in arsenic-induced genotoxicity where reduced glutathione (GSH) could be an important determining factor. To understand the role of endogenous GSH, arsenic trioxide (As2O3) was administered in buthionine sulfoximine (BSO)- and N-acetyl-L-cysteine (NAC)-treated mice. As2O3-induced significant chromosome aberrations (CAs) in all treatment groups compared with the control. BSO-treated mouse bone marrow cells showed significant CAs at a dose of 2 mg As2O3 kg(-1) b.w. Similar induction was not evident at 4 mg As2O3 kg(-1) b.w. and exhibited antagonistic effect at 8 mg As2O3 kg(-1) b.w. To understand this differential effect, expression pattern of Nrf2 was observed. Nrf2 expression increased following As2O3 treatment in a dose-dependent manner up to 4 mg As2O3 kg(-1) b.w after which no further increase was noticed. NAC pre-treatment significantly reduced the extent of As2O3-induced CAs suggesting the protective role of endogenous GSH against arsenic-induced genotoxicity. PMID:25906049

  19. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.

    PubMed

    Martelli, Maria Paola; Gionfriddo, Ilaria; Mezzasoma, Federica; Milano, Francesca; Pierangeli, Sara; Mulas, Floriana; Pacini, Roberta; Tabarrini, Alessia; Pettirossi, Valentina; Rossi, Roberta; Vetro, Calogero; Brunetti, Lorenzo; Sportoletti, Paolo; Tiacci, Enrico; Di Raimondo, Francesco; Falini, Brunangelo

    2015-05-28

    Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. PMID:25795919

  20. In Vivo Effect of Arsenic Trioxide on Keap1-p62-Nrf2 Signaling Pathway in Mouse Liver: Expression of Antioxidant Responsive Element-Driven Genes Related to Glutathione Metabolism

    PubMed Central

    Srivastava, Ritu; Sengupta, Archya; Mukherjee, Sandip; Chatterjee, Sarmishtha; Sudarshan, Muthammal; Chakraborty, Anindita; Bhattacharya, Shelley; Chattopadhyay, Ansuman

    2013-01-01

    Arsenic is a Group I human carcinogen, and chronic arsenic exposure through drinking water is a major threat to human population. Liver is one of the major organs for the detoxification of arsenic. The present study was carried out in mice in vivo after arsenic treatment through drinking water at different doses and time of exposure. Arsenic toxicity is found to be mediated by reactive oxygen species. Nuclear factor (erythroid-2 related) factor 2 (Nrf2)/Keap1 (Kelch-like ECH-associated protein 1)/ARE (antioxidant response element)—driven target gene system protects cells against oxidative stress and maintains cellular oxidative homeostasis. Our result showed 0.4 ppm, 2 ppm, and 4 ppm arsenic trioxide treatment through drinking water for 30 days and 90 days induced damages in the liver of Swiss albino mice as evidenced by histopathology, disturbances in liver function, induction of heat shock protein 70, modulation of trace elements, alteration in reduced glutathione level, glutathione-s-transferase and catalase activity, malondialdehyde production, and induction of apoptosis. Cellular Nrf2 protein level and mRNA level increased in all treatment groups. Keap1 protein as well as mRNA level decreased concomitantly in arsenic treated mice. Our study clearly indicates the important role of Nrf2 in activating ARE driven genes related to GSH metabolic pathway and also the adaptive response mechanisms in arsenic induced hepatotoxicity. PMID:27335833

  1. Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro.

    PubMed

    Pastorek, M; Gronesova, P; Cholujova, D; Hunakova, L; Bujnakova, Z; Balaz, P; Duraj, J; Lee, T C; Sedlak, J

    2014-01-01

    The aim of the present study was to compare the effect of realgar nanoparticles and arsenic trioxide (ATO) on viability, DNA damage, proliferation, autophagy and apoptosis in the human melanoma cell lines BOWES and A375. The application of various flow cytometric methods for measurements cell viability, DNA cell cycle, mitochondrial potential, lysosomal activity, and intracellular content of glutathione was used. In addition, quantitative PCR, western blotting and multiplex bead array analyses were applied for evaluation of redox stress, autophagic flux, and cell signaling alterations.The results showed that realgar treatment of studied cells caused modulation of cell proliferation, induced a block in G2/M phase of the cell cycle and altered phosphorylation of IκB, Akt, ERK1/2, p38, and JNK kinases, as well as decreased mitochondrial membrane potential. Additionally, it appeared that induction of cell death by both realgar and ATO was dose-dependent, when lower (0.3 µM) dosage increased lysosomal activity and induced autophagy and higher (1.25 µM) concentration resulted in the appearance of apoptosis, while pan-caspase inhibitor attenuated more efficiently realgar- than ATO-induced cell death. Furthermore, low concentrations of ATO and realgar nanoparticles increased the content of intracellular glutathione and elevated γ-H2AX expression confirmed DNA damage preferentially at higher concentrations of both drugs used. Further analysis revealed slight differences in time-dependent phosphorylation pattern due to both realgar and ATO treatments, while significant differences were noticed between cell lines. In conclusion, realgar nanoparticles and ATO treatment induced dose-dependent activation of autophagy and apoptosis in both melanoma cell lines, when autophagy flux was determined at lower drug concentrations and the switch to apoptosis occurred at higher concentrations of both arsenic forms. PMID:25150315

  2. Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells

    PubMed Central

    Liu, Da; Wu, Donglu; Zhao, Linhong; Yang, Yang; Ding, Jian; Dong, Liguo; Hu, Lianghai; Wang, Fei; Zhao, Xiaoming; Cai, Yong; Jin, Jingji

    2015-01-01

    Histone post-translational modification heritably regulates gene expression involved in most cellular biological processes. Experimental studies suggest that alteration of histone modifications affects gene expression by changing chromatin structure, causing various cellular responses to environmental influences. Arsenic (As), a naturally occurring element and environmental pollutant, is an established human carcinogen. Recently, increasing evidence suggests that As-mediated epigenetic mechanisms may be involved in its toxicity and carcinogenicity, but how this occurs is still unclear. Here we present evidence that suggests As-induced global histone H4K16 acetylation (H4K16ac) partly due to the direct physical interaction between As and histone acetyltransferase (HAT) hMOF (human male absent on first) protein, leading to the loss of hMOF HAT activity. Our data show that decreased global H4K16ac and increased deacetyltransferase HDAC4 expression occurred in arsenic trioxide (As2O3)-exposed HeLa or HEK293T cells. However, depletion of HDAC4 did not affect global H4K16ac, and it could not raise H4K16ac in cells exposed to As2O3, suggesting that HDAC4 might not directly be involved in histone H4K16 de-acetylation. Using As-immobilized agarose, we confirmed that As binds directly to hMOF, and that this interaction was competitively inhibited by free As2O3. Also, the direct interaction of As and C2CH zinc finger peptide was verified by MAIDI-TOF mass and UV absorption. In an in vitro HAT assay, As2O3 directly inhibited hMOF activity. hMOF over-expression not only increased resistance to As and caused less toxicity, but also effectively reversed reduced H4K16ac caused by As exposure. These data suggest a theoretical basis for elucidating the mechanism of As toxicity. PMID:26473953

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24160850

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

    PubMed

    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. PMID:24160850

  5. Down-regulation of Mcl-1 through GSK-3β activation contributes to arsenic trioxide-induced apoptosis in acute myeloid leukemia cells

    PubMed Central

    Wang, Rui; Xia, Lijuan; Gabrilove, Janice; Waxman, Samuel; Jing, Yongkui

    2012-01-01

    Arsenic trioxide (ATO) induces disease remission in acute promyelocytic leukemia (APL) patients, but not in non-APL acute myeloid leukemia (AML) patients. ATO at therapeutic concentrations (1-2 μM) induce APL NB4, but not non-APL HL-60, cells to undergo apoptosis through the mitochondrial pathway. The role of antiapoptotic protein Mcl-1 in ATO-induced apoptosis was determined. The levels of Mcl-1 were decreased in NB4, but not in HL-60, cells after ATO treatment through proteasomal degradation. Both GSK3β inhibitor SB216763 and siRNA blocked ATO-induced Mcl-1 reduction as well as attenuated ATO-induced apoptosis in NB4 cells. Silencing Mcl-1 sensitized HL-60 cells to ATO-induced apoptosis. Both ERK and AKT inhibitors decreased Mcl-1 levels and enhanced ATO-induced apoptosis in HL-60 cells. Sorafenib, a Raf inhibitor, activated GSK3β by inhibiting its phosphorylation, decreased Mcl-1 levels, and decreased intracellular glutathione levels in HL-60 cells. Sorafenib plus ATO augmented ROS production and apoptosis induction in HL-60 cells and in primary AML cells. These results indicate that ATO induces Mcl-1 degradation through activation of GSK3β in APL cells and provide a rationale for utilizing ATO in combination with sorafenib for the treatment of non-APL AML patients. PMID:22751450

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

    SciTech Connect

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na; Choe, Tae-Boo; Hong, Seok-Il; Yi, Jae-Youn; Hwang, Sang-Gu; Lee, Hyun-Gyu; Lee, Yun-Han; Park, In-Chul

    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.

  7. Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells.

    PubMed

    Zhang, Yao; Sun, Miao; Shi, Weiwei; Yang, Qingling; Chen, Changjie; Wang, Zhiwei; Zhou, Xin

    2015-01-22

    Acute promyelocytic leukemia (APL) is largely caused by the t(15,17) chromosome translocation, leading to the production of the PML/retinoic acid receptor alpha fusion. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), as a monotherapy or combination therapy, have been successfully used to treat APL primarily by targeting the degradation of the fusion protein. We previously observed that ATO treatment induced cell death in APL cell line HL-60 accompanied by inhibition of the human telomere reverse transcriptase (hTERT) activity, a critical enzyme responsible for the control of cell replication and transformation in cancer cells. In the present study, we investigated the underlying mechanism by which hTERT activity is inhibited by ATO in HL-60 cells. Our results showed that ATO down-regulated the expression of hTERT at both mRNA and protein levels. Further molecular analysis revealed that the expression of four transcription factors Sp1, c-Myc, NF-κB and USF2, which are located in the proximate promoter region (-1126 to -47) of hTERT, was also suppressed by ATO. Notably, we observed that down-regulation of these four factors by their siRNAs potentiates ATO-induced cell growth inhibition and apoptosis. Therefore, our results provide a novel mechanism of action of ATO for the treatment of APL. PMID:25436934

  8. Ultrastructural localization of F-actin using phalloidin and quantum dots in HL-60 promyelocytic leukemia cell line after cell death induction by arsenic trioxide.

    PubMed

    Izdebska, Magdalena; Gagat, Maciej; Grzanka, Dariusz; Grzanka, Alina

    2013-06-01

    Quantum dots (QDs) are fluorescent nanocrystals whose unique properties are fundamentally different from organic fluorophores. Moreover, their cores display sufficient electron density to be visible under transmission electron microscopy (TEM). Here, we report a technique for phalloidin-based TEM detection of F-actin. The ultrastructural reorganization of F-actin after arsenic trioxide (ATO) treatment was estimated using a combination of pre- and post-embedding techniques with biotinylated phalloidin and QD-streptavidin conjugates or colloidal gold (AU) conjugated to streptavidin. Ultrastructural studies showed ATO-induced apoptosis of HL-60 cells. Moreover, different patterns of QD-labeled F-actin after ATO treatment were seen. In the case of AU labeling, only a few gold particles were seen and it was impossible to see any difference in F-actin distribution. TEM imaging experiments using QDs and colloidal gold (AU) showed that the strategy of bioconjugation of nanoprobes is the most important factor in biotinylated phalloidin detection of F-actin using streptavidin-coated nanoparticles, especially at the ultrastructural level. Additionally, the results presented in present study confirm the essential role of F-actin in chromatin reorganization during cell death processes. PMID:23312591

  9. Ultrasensitive and selective assay of glutathione species in arsenic trioxide-treated leukemia HL-60 cell line by molecularly imprinted polymer decorated electrochemical sensors.

    PubMed

    Zhang, Bo; Liu, Jie; Ma, Xiaoru; Zuo, Peng; Ye, Bang-ce; Li, Yingchun

    2016-06-15

    Herein a pair of molecularly imprinted polymer (MIP) modified electrochemical sensors were reported to detect glutathione (GSH) and glutathione disulfide (GSSG) in arsenic trioxide-treated HL-60 cells. MIP film was in situ synthesized onto electrode surface via electro-polymerization in a facile way. The characteristics of the obtained sensors were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Both GSH-MIP and GSSG-MIP sensors exhibit the relatively wide linear detection range and low detection limit of 1.33 × 10(-10) M (S/N=3). It is found that N-acetylcysteine and DL-homocysteine, the precursors of GSH, show little influence on the detection of glutathione species, nor did the reactants of arsenite and GSH. Such strategies were successfully applied to discriminate GSH and GSSG in cell samples with acceptable recoveries of 92.0-109.1%, and the results are comparable with classic o-phthalaldehyde fluorospectrophotometry. Moreover, the presented sensors allow for easy disclosure of the reversion of malignant phenotype in leukemia cells via glutathione species analysis. PMID:26890824

  10. Acute promyelocytic leukemia with isochromosome 17q and cryptic PML-RARA successfully treated with all-trans retinoic acid and arsenic trioxide.

    PubMed

    Shepshelovich, Daniel; Oniashvili, Nino; Parnes, Doris; Klein, Alina; Muchtar, Eli; Yeshaya, Josepha; Aviram, Adina; Rabizadeh, Esther; Raanani, Pia

    2015-11-01

    Acute promyelocytic leukemia (APL) is a subtype of acute leukemia that is characterized by typical morphology, bleeding events and distinct chromosomal aberrations, usually the t(15;17)(q22;q21) translocation. Approximately 9% of APL patients harbor other translocations involving chromosome 17, such as the t(11;17)(q23;q21), t(5;17)(q35;q12-21), t(11;17)(q13;q21), and der(17). All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have specific targeted activities against the PML-RARA fusion protein. The combination of ATRA and ATO is reportedly superior to chemotherapy and ATRA as induction therapy for APL. The clinical significance of non-t(15:17) APL-related aberrations is controversial, with conflicting reports regarding sensitivity to modern, targeted therapy. Isochromosome 17q (iso(17q)) is rarely associated with APL and usually occurs concurrently with the t(15:17) translocation. No published data is available regarding the efficacy of ATO-based therapy for APL patients who harbor iso(17q). We report on an APL patient with iso(17q) as the sole cytogenetic aberration and a cryptic PML-RARA transcript, who was treated with ATRA and ATO after failure of chemotherapy and achieved complete remission. To our knowledge, this is the first published report of APL associated with iso(17q) as the sole cytogenetic aberration, which was successfully treated with an ATO containing regimen. PMID:26471811

  11. Arsenic Trioxide (ATO) cooperates with All Trans Retinoic Acid (ATRA) to enhance MAPK activation and differentiation in Human Myeloblastic Leukemia (HL-60) cells

    PubMed Central

    Nayak, Satyaprakash; Shen, Miaoqing; Varner, Jeffrey D.; Yen, Andrew

    2016-01-01

    Arsenic trioxide (ATO) synergistically promotes retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells, a PML-RARα negative cell line. In PML-RARα positive myeloid leukemia cells, ATO is known to cause degradation of PML-RARα with subsequent induced myeloid differentiation. We find now that ATO by itself does not cause differentiation of the PML-RARα negative HL-60 cells, but enhances RA’s capability to cause differentiation. RA-induced differentiation of HL-60 cells is known to be propelled by an induced hyperactive/persistent MAPK signal. ATO augmented RA induced RAF/MEK/ERK axis signaling and expression of CD11b, an integrin receptor that is a myeloid differentiation marker. p47PHOX, a component of the respiratory burst machinery and inducible oxidative metabolism, functional differentiation marker were also enhanced. However, ATO did not enhance RA-induced CD38 expression, an early cell surface differentiation marker. ATO enhanced RA-induced population growth retardation without evidence of apoptosis or an enhanced G1/0 growth arrest. But compared to RA, ATO plus RA showed reduced pAKT, suggesting that an overall biosynthetic/metabolic retardation was seminal to the apparent enhanced growth retardation due to ATO. In sum, our results indicate that ATO can augment action of RA in causing differentiation of myeloid leukemia cells through promoting MAPK signaling and independent of PML-RARα. PMID:20615082

  12. Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism.

    PubMed

    Ghaffari, Seyed H; Yousefi, Meysam; Dizaji, Majid Zaki; Momeny, Majid; Bashash, Davood; Zekri, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2016-01-01

    Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dosedependent manner and also inhibited classical NF-κB signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-κB and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-κB down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-κB-mediated inhibition of survivin and telomerase activity and NF-κB-dependent suppression of cathepsin B, MMP-2 and MMP-9. PMID:27039805

  13. Arsenic trioxide (As{sub 2}O{sub 3}) induced calcium signals and cytotoxicity in two human cell lines: SY-5Y neuroblastoma and 293 embryonic kidney (HEK)

    SciTech Connect

    Florea, Ana-Maria; Splettstoesser, Frank; Buesselberg, Dietrich . E-mail: Dietrich.Buesselberg@uni-due.de

    2007-05-01

    Arsenic trioxide (As{sub 2}O{sub 3}) has anticancer properties; however, its use also leads to neuro-, hepato- or nephro-toxicity, and therefore, it is important to understand the mechanism of As{sub 2}O{sub 3} toxicity. We studied As{sub 2}O{sub 3} influence on intracellular calcium ([Ca{sup 2+}]{sub i}) homeostasis of human neuroblastoma SY-5Y and embryonic kidney cells (HEK 293).We also relate the As{sub 2}O{sub 3} induced [Ca{sup 2+}]{sub i} modifications with cytotoxicity. We used Ca{sup 2+} sensitive dyes (fluo-4 and rhod-2) combined with laser scanning microscopy or fluorescence activated cell sorting to measure Ca{sup 2+} changes during the application of As{sub 2}O{sub 3} and we approach evaluation of cytotoxicity. As{sub 2}O{sub 3} (1 {mu}M) increased [Ca{sup 2+}]{sub i} in SY-5Y and HEK 293 cells. Three forms of [Ca{sup 2+}]{sub i}-elevations were found: (1) steady-state increases (2) transient [Ca{sup 2+}]{sub i}-elevations and (3) Ca{sup 2+}-spikes. [Ca{sup 2+}]{sub i} modifications were independent from extracellular Ca{sup 2+} but dependent on internal calcium stores. The effect was not reversible. Inositol triphosphate (IP{sub 3}) and ryanodine (Ry) receptors are involved in regulation of signals induced by As{sub 2}O{sub 3}. 2-APB and dantrolene significantly reduced the [Ca{sup 2+}]{sub i}-rise (p < 0.001, t-test) but did not completely abolish [Ca{sup 2+}]{sub i}-elevation or spiking. This indicates that other Ca{sup 2+} regulating mechanisms are involved. In cytotoxicity tests As{sub 2}O{sub 3} significantly reduced cell viability in both cell types. Staining with Hoechst 33342 showed occurrence of apoptosis and DNA damage. Our data suggest that [Ca{sup 2+}]{sub i} is an important messenger in As{sub 2}O{sub 3} induced cell death.

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

    PubMed Central

    Ma, Yafang; Liu, Lu; Jin, Jie; Lou, Yinjun

    2016-01-01

    Background 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. Methods We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity. Results 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). Conclusion 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. PMID:27391027

  15. PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells.

    PubMed

    Jo, Sungsin; Lee, Young Lim; Kim, Sojin; Lee, Hongki; Chung, Heekyoung

    2016-07-01

    Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1, via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down-regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation-, ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein. Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I-mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition, UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise, endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. PMID:27030546

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

    SciTech Connect

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling; Yeh, Bi-Wen; Wu, Wen-Jeng; Huang, Huei-Sheng

    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 mediates

  17. Arsenic

    MedlinePlus

    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- ...

  18. Arsenic

    MedlinePlus

    ... and minerals. Arsenic compounds are used to preserve wood, as pesticides, and in some industries. Arsenic can ... Breathing sawdust or burning smoke from arsenic-treated wood Living in an area with high levels of ...

  19. Antimony trioxide

    Integrated Risk Information System (IRIS)

    Antimony trioxide ; CASRN 1309 - 64 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  20. 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

    PubMed Central

    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

  1. Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines.

    PubMed

    Sánchez, Yolanda; Simón, Gloria P; Calviño, Eva; de Blas, Elena; Aller, Patricio

    2010-10-01

    Arsenic trioxide (ATO, Trisenox) is an important antileukemic drug, but its efficacy is frequently low when used as a single agent. Here, we demonstrate that the apoptotic action of ATO is greatly increased when combined with subcytotoxic curcumin concentrations in U937 and HL60 human acute myeloid leukemia cells, and with lower efficacy in K562 chronic myelogenous leukemia cells. Curcumin exerts similar cooperative effect with the mitochondria-targeting drug lonidamine, whereas the response is negligible in combination with the DNA-targeting drug cisplatin. Curcumin plus ATO or lonidamine stimulates typical events of the mitochondrial executioner pathway (Bax and Bid activation, cytochrome c release, X-linked inhibitor of apoptosis down-regulation, and caspase-9/-3 activation) and causes mitochondrial transmembrane potential dissipation, which nevertheless represents a late event in the apoptotic response. Curcumin increases anion superoxide production, and its proapoptotic action in combination with ATO and lonidamine is mimicked by pro-oxidant agents (2-methoxyestradiol and H(2)O(2)) and prevented by antioxidant agents [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride and N-acetyl-l-cysteine]. Within the assayed time period (16-24 h), curcumin does not significantly modify p38-mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase phosphorylation/activation or nuclear factor-κB activity, but it greatly stimulates extracellular signal-regulated kinase (ERK) phosphorylation, and decreases Akt phosphorylation. Experiments using mitogen-activated protein kinase kinase/ERK inhibitors [2'-amino-3'-methoxyflavone (PD98059) and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126)] and phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) indicate that ERK activation does not mediate and even restrains apoptosis potentiation, whereas Akt down-regulation facilitates apoptosis generation. In summary

  2. 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.

    PubMed

    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

  3. Arsenic

    MedlinePlus

    ... mainly found in its less toxic organic form. Industrial processes Arsenic is used industrially as an alloying ... are also required to reduce occupational exposure from industrial processes. Education and community engagement are key factors ...

  4. Bone marrow stroma-induced resistance of chronic lymphocytic leukemia cells to arsenic trioxide involves Mcl-1 upregulation and is overcome by inhibiting the PI3Kδ or PKCβ signaling pathways.

    PubMed

    Amigo-Jiménez, Irene; Bailón, Elvira; Aguilera-Montilla, Noemí; Terol, María José; García-Marco, José A; García-Pardo, Angeles

    2015-12-29

    CLL remains an incurable disease in spite of the many new compounds being studied. Arsenic trioxide (ATO) induces apoptosis in all CLL cell types and could constitute an efficient therapy. To further explore this, we have studied the influence of stromal cells, key components of the CLL microenvironment, on the response of CLL cells to ATO. Bone marrow stromal cells induced CLL cell resistance to 2 μM ATO and led to activation of Lyn, ERK, PI3K and PKC, as well as NF-κB and STAT3. Mcl-1, Bcl-xL, and Bfl-1 were also upregulated after the co-culture. Inhibition experiments indicated that PI3K and PKC were involved in the resistance to ATO induced by stroma. Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kδ and PKCβ, respectively, inhibited Akt phosphorylation, NF-κB/STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO. Mcl-1 was central to the mechanism of resistance to ATO, since: 1) Mcl-1 levels correlated with the CLL cell response to ATO, and 2) blocking Mcl-1 expression or function with specific siRNAs or inhibitors overcame the protecting effect of stroma. We have therefore identified the mechanism involved in the CLL cell resistance to ATO induced by bone marrow stroma and show that idelalisib or sotrastaurin block this mechanism and restore sensibility to ATO. Combination of ATO with these inhibitors may thus constitute an efficient treatment for CLL. PMID:26540567

  5. Bone marrow stroma-induced resistance of chronic lymphocytic leukemia cells to arsenic trioxide involves Mcl-1 upregulation and is overcome by inhibiting the PI3Kδ or PKCβ signaling pathways

    PubMed Central

    Amigo-Jiménez, Irene; Bailón, Elvira; Aguilera-Montilla, Noemí; Terol, María José; García-Marco, José A.; García-Pardo, Angeles

    2015-01-01

    CLL remains an incurable disease in spite of the many new compounds being studied. Arsenic trioxide (ATO) induces apoptosis in all CLL cell types and could constitute an efficient therapy. To further explore this, we have studied the influence of stromal cells, key components of the CLL microenvironment, on the response of CLL cells to ATO. Bone marrow stromal cells induced CLL cell resistance to 2 μM ATO and led to activation of Lyn, ERK, PI3K and PKC, as well as NF-κB and STAT3. Mcl-1, Bcl-xL, and Bfl-1 were also upregulated after the co-culture. Inhibition experiments indicated that PI3K and PKC were involved in the resistance to ATO induced by stroma. Moreover, idelalisib and sotrastaurin, specific inhibitors for PI3Kδ and PKCβ, respectively, inhibited Akt phosphorylation, NF-κB/STAT3 activation and Mcl-1 upregulation, and rendered cells sensitive to ATO. Mcl-1 was central to the mechanism of resistance to ATO, since: 1) Mcl-1 levels correlated with the CLL cell response to ATO, and 2) blocking Mcl-1 expression or function with specific siRNAs or inhibitors overcame the protecting effect of stroma. We have therefore identified the mechanism involved in the CLL cell resistance to ATO induced by bone marrow stroma and show that idelalisib or sotrastaurin block this mechanism and restore sensibility to ATO. Combination of ATO with these inhibitors may thus constitute an efficient treatment for CLL. PMID:26540567

  6. PREPARATION OF URANIUM TRIOXIDE

    DOEpatents

    Buckingham, J.S.

    1959-09-01

    The production of uranium trioxide from aqueous solutions of uranyl nitrate is discussed. The uranium trioxide is produced by adding sulfur or a sulfur-containing compound, such as thiourea, sulfamic acid, sulfuric acid, and ammonium sulfate, to the uranyl solution in an amount of about 0.5% by weight of the uranyl nitrate hexahydrate, evaporating the solution to dryness, and calcining the dry residue. The trioxide obtained by this method furnished a dioxide with a considerably higher reactivity with hydrogen fluoride than a trioxide prepared without the sulfur additive.

  7. Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation.

    PubMed

    Calviño, Eva; Estañ, María Cristina; Simón, Gloria P; Sancho, Pilar; Boyano-Adánez, María del Carmen; de Blas, Elena; Bréard, Jacqueline; Aller, Patricio

    2011-12-01

    Lonidamine is a safe, clinically useful anti-tumor drug, but its efficacy is generally low when used in monotherapy. We here demonstrate that lonidamine efficaciously cooperates with the anti-leukemic agent arsenic trioxide (ATO, Trisenox) to induce apoptosis in HL-60 and other human leukemia cell lines, with low toxicity in non-tumor peripheral blood lymphocytes. Apoptosis induction by lonidamine/ATO involves mitochondrial dysfunction, as indicated by early mitochondrial permeability transition pore opening and late mitochondrial transmembrane potential dissipation, as well as activation of the intrinsic apoptotic pathway, as indicated by Bcl-X(L) and Mcl-1 down-regulation, Bax translocation to mitochondria, cytochrome c and Omi/HtrA2 release to the cytosol, XIAP down-regulation, and caspase-9 and -3 cleavage/activation, with secondary (Bcl-2-inhibitable) activation of the caspase-8/Bid axis. Lonidamine stimulates reactive oxygen species production, and lonidamine/ATO toxicity is attenuated by antioxidants. Lonidamine/ATO stimulates JNK phosphorylation/activation, and apoptosis is attenuated by the JNK inhibitor SP600125. In addition, lonidamine elicits ERK and Akt/mTOR pathway activation, as indicated by increased ERK, Akt, p70S6K and rpS6 phosphorylation, and these effects are reduced by co-treatment with ATO. Importantly, co-treatment with MEK/ERK inhibitor (U0126) and PI3K/Akt (LY294002) or mTOR (rapamycin) inhibitors, instead of ATO, also potentiates lonidamine-provoked apoptosis. These results indicate that: (i) lonidamine efficacy is restrained by drug-provoked activation of MEK/ERK and Akt/mTOR defensive pathways, which therefore represent potential therapeutic targets. (ii) Co-treatment with ATO efficaciously potentiates lonidamine toxicity via defensive pathway inhibition and JNK activation. And (iii) conversely, the pro-oxidant action of lonidamine potentiates the apoptotic efficacy of ATO as an anti-leukemic agent. PMID:21889928

  8. 2-Deoxy-D-glucose cooperates with arsenic trioxide to induce apoptosis in leukemia cells: involvement of IGF-1R-regulated Akt/mTOR, MEK/ERK and LKB-1/AMPK signaling pathways.

    PubMed

    Estañ, María Cristina; Calviño, Eva; de Blas, Elena; Boyano-Adánez, María del Carmen; Mena, Maria Luz; Gómez-Gómez, Milagros; Rial, Eduardo; Aller, Patricio

    2012-12-15

    While the anti-tumor efficacy of 2-deoxy-D-glucose (2-DG) is normally low in monotherapy, it may represent a valuable radio- and chemo-sensitizing agent. We here demonstrate that 2-10 mM 2-DG cooperates with arsenic trioxide (ATO) and other antitumor drugs to induce apoptosis in human myeloid leukemia cell lines. Using ATO and HL60 as drug and cell models, respectively, we observed that 2-DG/ATO combination activates the mitochondrial apoptotic pathway, as indicated by Bid-, and Bax-regulated cytochrome c and Omi/HtrA2 release, XIAP down-regulation, and caspase-9/-3 pathway activation. 2-DG neither causes oxidative stress nor increases ATO uptake, but causes inner mitochondria membrane permeabilization as well as moderate ATP depletion, which nevertheless do not satisfactorily explain the pro-apoptotic response. Surprisingly 2-DG causes cell line-specific decrease in LKB-1/AMPK phosphorylation/activation, and also causes Akt/mTOR/p70S6K and MEK/ERK activation, which is prevented by co-treatment with ATO. The use of kinase-specific pharmacologic inhibitors and/or siRNAs reveals that apoptosis is facilitated by AMPK inactivation and restrained by Akt and ERK activation, and that Akt and ERK activation mediates AMPK inhibition. Finally, 2-DG stimulates IGF-1R phosphorylation/activation, and co-treatment with IGF-1R inhibitor prevents 2-DG effects on Akt, ERK and AMPK, and facilitates 2-DG-provoked apoptosis. In summary 2-DG elicits IGF-1R-mediated AMPK inactivation and Akt and ERK activation, which facilitates or restrain apoptosis, respectively. 2-DG-provoked AMPK inactivation increases the apoptotic efficacy of ATO, while in turn ATO-provoked Akt and ERK inactivation may increase the efficacy of 2-DG as anti-tumor drug. PMID:23041229

  9. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  10. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  11. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  12. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  13. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  14. Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals.

    PubMed

    Fan, Xiao-Yang; Chen, Xin-You; Liu, Yu-Jiao; Zhong, Hui-Min; Jiang, Feng-Lei; Liu, Yi

    2016-01-01

    Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC50) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs. PMID:27432798

  15. Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals

    PubMed Central

    Fan, Xiao-Yang; Chen, Xin-You; Liu, Yu-Jiao; Zhong, Hui-Min; Jiang, Feng-Lei; Liu, Yi

    2016-01-01

    Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC50) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs. PMID:27432798

  16. Arsenic trioxide (As(2)O(3)) induces apoptosis and necrosis mediated cell death through mitochondrial membrane potential damage and elevated production of reactive oxygen species in PLHC-1 fish cell line.

    PubMed

    Selvaraj, Vellaisamy; Armistead, Mindy Yeager; Cohenford, Menashi; Murray, Elizabeth

    2013-01-01

    Several environmental pollutants, including metals can induce toxicological effect on aquatic animal species. Most studies to understand the toxicity of arsenic compounds were performed in mammalian cells; however, the study of the arsenic toxicity to the aquatic animals' species, including fish, is limited. So the objective of this study was first to investigate the effects of As(2)O(3) induced toxicity particularly on apoptosis and necrosis mediated cell death in fish cell PLHC-1 as compared to the mechanism of toxicity from known mammalian cell lines, secondly to relate in vitro effects in fish to those demonstrated by in vivo systems. To conduct this study, PLHC-1 cells were exposed to various concentrations of As(2)O(3) (0-100 μM) for 10, 20 and 40 h. The results indicate that As(2)O(3) exposure promoted apoptotic and necrotic mediated cell death in a concentration and time dependent manner. Cell death (apoptotic and necrotic) induced by As(2)O(3) was further confirmed by changes in various phases of cell cycle, DNA fragmentation (necro- comet and apo-comet) in the comet assay, alteration in mitochondrial membrane potential and formation of increased reactive oxygen species (ROS). Apoptotic mediated cell death was confirmed further by observing the increased caspase-3 activity and elevated expression of p53, cytochrome c and Bax proteins levels in the same experimental conditions. PLHC-1 cells were shown to be a good model for evaluating biochemical/cytotoxic effects following exposure to various reference chemicals and environmental contaminants. In vitro data obtained from this study provides a comprehensive approach for the elucidating the actual molecular mechanism for As(2)O(3) induced toxicity particularly apoptosis and necrosis mediated cell death in PLHC-1 cell line. PMID:23121984

  17. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  18. Arsenic Induces Functional Re-Expression of Estrogen Receptor α by Demethylation of DNA in Estrogen Receptor-Negative Human Breast Cancer

    PubMed Central

    Liu, Hongxia; Jiang, Fei; Wang, Yubang; Hu, Chunyan; Qi, Hong; Zhong, Caiyun; Wang, Xinru; Li, Zhong

    2012-01-01

    Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)- 2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER–negative human breast cancer. PMID:22558281

  19. ARSENIC EFFECTS ON TELOMERE AND TELOMERASE ACTIVITY

    EPA Science Inventory

    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 27711
    Arsenic is a known carcinogen and also an anticancer agent for acut...

  20. Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

    PubMed

    Farmer, J G; Johnson, L R

    1990-05-01

    An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases. PMID:2357455

  1. Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

    PubMed Central

    Farmer, J G; Johnson, L R

    1990-01-01

    An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases. PMID:2357455

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

    PubMed Central

    Zhang, Tao; Lu, Haojie; Li, Weijun; Hu, Ronggui; Chen, Zi

    2015-01-01

    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. PMID:26569224

  3. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    NASA Astrophysics Data System (ADS)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  4. Arsenic Methyltransferase

    EPA Science Inventory

    The metalloid arsenic enters the environment by natural processes (volcanic activity, weathering of rocks) and by human activity (mining, smelting, herbicides and pesticides). Although arsenic has been exploited for homicidal and suicidal purposes since antiquity, its significan...

  5. ARSENIC REMOVAL

    EPA Science Inventory

    Presentation covered five topics; arsenic chemistry, best available technology (BAT), surface water technology, ground water technology and case studies of arsenic removal. The discussion on arsenic chemistry focused on the need and method of speciation for AsIII and AsV. BAT me...

  6. A spectroscopic study of the impact of arsenic speciation on arsenic/phosphorous uptake and plant growth in tumbleweed (Salsola kali)

    PubMed Central

    de la Rosa, Guadalupe; Parsons, Jason G.; Martinez-Martinez, Alejandro; Peralta-Videa, Jose R.; Gardea-Torresdey, Jorge L.

    2008-01-01

    This manuscript reports the toxic effects of As2O3 (arsenic trioxide) and As2O5 (arsenic pentoxide) on S. kali, as well as the arsenic and phosphate uptake, and arsenic coordination within plant tissues. Plants were germinated and grown for 15 days on a Hoagland modified medium containing either As(III) (arsenic trioxide) or As(V) (arsenic pentoxide). Subsequently, the seedlings were measured and analyzed using ICP-OES and XAS techniques. Plants stressed with 2 mg L−1 of whichever As(III) or As(V) concentrated 245 ± 19, 30 ± 1, and 60 ± 3 mg As kg−1 d. wt, or 70 ± 6, 10 ± 0.3, and 27 ± 3 mg As kg−1 d. wt in roots, stems, and leaves, respectively. Arsenate was less toxic and more As translocation occurred from the roots to the leaves. All treatments reduced P concentration at root level; however, only As(V) at 2 and 4 mg L−1 reduced P concentration at leaf level. Regardless the arsenic species supplied to the plants, arsenic was found in plant tissues as As(III) coordinated to three sulfur ligands with an interatomic distance of approximately 2.25 Å. PMID:16570626

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26598702

  8. Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

    PubMed Central

    Yager, J W; Hicks, J B; Fabianova, E

    1997-01-01

    Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. Images Figure 1. A Figure 1. B Figure 2. PMID:9347899

  9. Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

    PubMed

    Yager, J W; Hicks, J B; Fabianova, E

    1997-08-01

    Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. PMID:9347899

  10. Polyol mediated synthesis of tungsten trioxide and Ti doped tungsten trioxide

    SciTech Connect

    Porkodi, P.; Yegnaraman, V.; Jeyakumar, D. . E-mail: djkr@rediffmail.com

    2006-08-10

    Polyol mediated synthesis for the preparation of tungsten trioxide and titanium doped tungsten trioxide has been reported. The reaction was carried out using chlorides of tungsten and titanium in diethylene glycol medium and water as the reagent for hydrolysis at 190 deg. C. Formation of a blue coloured dimensionally stable suspension of the precursor materials was observed during the course of the reaction. The particle sizes of the precursor materials were observed to be around 100 nm. The precursor materials were annealed to give tungsten trioxide and titanium doped tungsten trioxide. The precursor materials were characterised using TGA/DTA, FT-IR, optical spectra, SEM, TEM and powder XRD methods. It was observed that the doping of titanium could be effected at least up to 10% of Ti in WO{sub 3}. The TGA/DTA studies indicated that WO{sub 3-x}.H{sub 2}O is the dominant material that formed during the polyol mediated synthesis. The XRD data of the annealed samples revealed that the crystalline phase could be manipulated by varying the extent of titanium doping in the tungsten trioxide matrix.

  11. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

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

    PubMed

    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. PMID:26716387

  13. [Exposure to arsenic in the manufacture of glass rods. Results of the biological monitoring and preventive indications].

    PubMed

    Montagnani, R; Campagna, M; Gasparello, S; Hreiglich, A; Apostoli, P

    2006-01-01

    Nowadays arsenic trioxid is still used in the hand made glass production in Murano. In the last years, many industries have reduced its use but, in some specific lines of production, such as the "bacchetta di vetro" for the secondary "a lume" production, there is still a considerable use. Biological monitoring, carried out through urinary arsenic measurement, shows as workers employed in the mixture preparation and in the furnace work, are still significantly exposed to arsenic, despite the technical preventive measures adopted. We propose further measures to reduce this risk. PMID:16805446

  14. Organic transformations catalyzed by methylrhenium trioxide

    SciTech Connect

    Zhu, Z.

    1995-11-01

    Methylrhenium trioxide (MTO), CH{sub 3}ReO{sub 3}, was first prepared in 1979. MTO forms stable or unstable adducts with electron-rich ligands, such as amines (quinuclidine, 1,4-diazabicyclo-octane, pyridine, aniline, 2,2{prime}-bipyridine), alkynes, olefins, 1,2-diols, catechols, hydrogen peroxide, water, thiophenols, 1,2-dithiols, triphenylphosphine, 2-aminophenols, 2-aminothiophenols, 8-hydroxyquinoline and halides (Cl-, Br-, I-). After coordination, different further reactions will occur for different reagents. Reactions described in this report include the dehydration of alcohols, direct amination of alcohols, activation of hydrogen peroxide, oxygen transfer, and decomposition of ethyl diazoacetate.

  15. The MRP1-mediated effluxes of arsenic and antimony do not require arsenic-glutathione and antimony-glutathione complex formation.

    PubMed

    Salerno, Milena; Petroutsa, Maria; Garnier-Suillerot, Arlette

    2002-04-01

    Arsenic trioxide is an effective treatment for acute promyelocytic leukemia, but resistance to metalloid salts is found in humans. Using atomic absorption spectroscopy, we have measured the rate of uptake of arsenic trioxide and of antimony tartrate in GLC4 and GLC4/ADR cells overexpressing MRP1 and the rate of their MRP1-mediated effluxes as a function of the intracellular GSH concentration. In sensitive cells, after 1 h, a pseudosteady state is reached where intra- and extracellular concentrations of metalloid are the same. This precludes the formation, at short term, of complexes between arsenic or antimony with GSH. In resistant cells reduced intracellular accumulation of arsenic (or antimony), reflecting an increased rate of arsenic (or antimony) efflux from the cells, is observed. No efflux of the metalloid is observed in GSH depleted cells. The two metalloids and GSH are pumped out by MRP1 with the same efficiency. Moreover for the three compounds 50% of the efflux is inhibited by 2 microM MK571. This led us to suggest that As- and Sb-containing species could be cotransported with GSH. PMID:12018890

  16. Phase Transformations upon Doping in Tungsten Trioxide

    NASA Astrophysics Data System (ADS)

    Wang, Wennie; Janotti, Anderson; van de Walle, Chris G.

    Tungsten trioxide (WO3) is an emerging semiconductor material, with a growing number of applications in Li-ion batteries, photocatalysis, gas sensors and electrochromic devices. As an electrochromic material, WO3 turns from transparent to blue upon doping with monovalent species. Due to it having an empty A-site in the ABO3 perovskite structure, high doping concentrations are possible through intercalation. Tungsten trioxide has been experimentally shown to transform from the ground-state monoclinic symmetry to cubic symmetry with increasing monovalent doping. We use first-principles calculations to understand this transformation. Our calculations show that the addition of electrons to the conduction band is a primary driver of the phase transformation. We quantify the energetics and structural aspects of this transformation using density functional theory, allowing us to elucidate the mechanism. Comparison with experiment, role of the dopant species, and implications of structural changes for device applications will be discussed. This work is supported by the DOE and NSF GRFP.

  17. Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Steinmaus, Craig; Liaw, Jane; Smith, Martyn T.; Wood, Lily; Heirich, Marissa; Fritzemeier, Rebecca M.; Pegram, Mark D.; Ferreccio, Catterina

    2014-01-01

    Background Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970. Methods We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies. Findings Before 1958, breast cancer mortality rates were similar, but in 1958–1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51, 95% CI 0.40–0.66; p < 0.0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965–1970 (RR = 0.30, 0.17–0.54; p < 0.0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II. Interpretation We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer. PMID:25580451

  18. Total and Inorganic Arsenic in Mid-Atlantic Marine Fish and Shellfish and Implications for Fish Advisories

    SciTech Connect

    Greene, Richard; Crecelius, Eric A.

    2006-02-06

    Up to 33.3 metric tons of arsenic trioxide were spilled off the Middle Atlantic coast of the United States in January of 1992 during a shipping accident. Historical fish tissue data for samples collected in the Delaware Inland Bays before and after the spill reveal a prominent spike in total arsenic in summer flounder following the spill and a gradual decline ever since. In 2002, a small study was conducted to determine whether summer flounder migrating into the Delaware Inland Bays from the Continental Shelf in the spring contain higher body burdens of arsenic than summer flounder migrating out of the Inland Bays in the fall. Total arsenic was significantly higher in the incoming fish. Considering that summer flounder overwinter at the spill site, that arsenic trioxide is a dense powder of limited solubility that would tend to incorporate into the sediments, and that summer flounder are demersal fish, we conclude that summer flounder accumulate arsenic offshore and that the likely source of their extra body burden is the spilled arsenic. Speciation of arsenic in the summer flounder, as well as in Atlantic croaker, striped bass, and hard clam reveal low concentrations (0.5 ? 20 ug/kg ww) of toxic inorganic arsenic. DMA was more than an order of magnitude greater in hard clam meats than in the other species tested, a finding attributed to arsenic uptake by phytoplankton and subsequent dietary uptake by the clam. Risk assessment using the inorganic arsenic concentrations was used to conclude that a fish advisory is not warranted.

  19. Effect of iron redox transformations on arsenic solid-phase associations in an arsenic-rich, ferruginous hydrothermal sediment

    NASA Astrophysics Data System (ADS)

    Handley, Kim M.; McBeth, Joyce M.; Charnock, John M.; Vaughan, David J.; Wincott, Paul L.; Polya, David A.; Lloyd, Jonathan R.

    2013-02-01

    Well-constrained laboratory incubations of a ferruginous marine hydrothermal sediment from Santorini, Greece, were used to elucidate the effect of microbially induced redox transformations on arsenic speciation and mobility. Despite naturally high arsenic concentrations (˜400 mg/kg), the sediment has a low As:Fe ratio (1:1000 wt/wt). Acetate-amendment of sediment, extracted from the naturally-occurring suboxic-anoxic (Eh -60 to -138 mV) transition zone, promoted Fe(III) reduction, and increased the concentration of Fe(II) from ˜40% to ˜60% in the bulk sediment. Sulfate, which was present at lower concentrations, was also reduced. Phylogenetic 16S rRNA and dsr gene analysis suggested that Fe(III) and sulfate were reduced by bacteria related to Malonomonas rubra and Desulfosarcina variabilis, respectively. Arsenic remained predominantly as arsenic trioxide (As2O3) throughout the amendment experiment. However, the percentage of total arsenic present within poorly-crystalline iron oxides decreased from ˜69% to ˜32%, while the percentage incorporated within crystalline iron-containing minerals or sorbed to surfaces via inner-sphere complexes increased significantly (to 22% and 30%, respectively). Re-oxidation of the system with nitrate resulted in incomplete reduction of the nitrate pool, and partial re-association of arsenic with the poorly-crystalline iron fraction. Exposure to air led to virtually complete reversal of the arsenic partitioning, and oxidation of 71% As(III) to As(V). During aeration, oxidation of sediment-bound sulfur/sulfide occurred, alongside an observed ˜63% decrease in arsenic bound to this minor component. Analogous trends in arsenic-sediment associations were observed in the natural, unamended sediment depth-profile, whereby a greater proportion of arsenic (34% As(III), 66% As(V)) was bound within poorly-crystalline iron oxides at the sediment-water interface. Arsenic (96% As(III)) was increasingly incorporated within well

  20. Arsenic and its combinations in cancer therapeutics.

    PubMed

    Prajapati, Vandana; Kale, Raosaheb K; Singh, Rana P

    2011-06-01

    Arsenic is a metalloid that is considered to be a paradox in terms of its role both as a carcinogen and as a therapeutic agent. Chronic exposure to arsenic in drinking water has been linked with the development of various pathological conditions including cancer. Nevertheless, the therapeutic potential of arsenic and its derivatives in a variety of diseases have been exploited in the past. However, its role and mechanism of action as a therapeutic agent still remain an active area of research and investigation. Our ongoing work also suggests varied responses in cancer cells exposed to lower versus higher concentrations of arsenic. Furthermore, the arsenic combinations with chemopreventive or anticancer agents have been observed to sensitize the cell for cell-cycle arrest and cell death. Here, we have provided the account of recent updates on the mechanism of action of arsenic and its derivatives that lead to various disorders, and its role as a therapeutic agent both as a single agent as well as in combination chemotherapy. PMID:22822509

  1. Arsenic, inorganic

    Integrated Risk Information System (IRIS)

    Arsenic , inorganic ; CASRN 7440 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  2. Can MTA be: Miracle trioxide aggregate?

    PubMed Central

    Naik, Reshma M; Pudakalkatti, Pushpa S; Hattarki, Sanjeevini A

    2014-01-01

    Mineral trioxide aggregate (MTA) has been used for more than 10 years in the dental community and has often been thought of as a material of choice for the endodontist. The dental pulp is closely related to periodontal tissues through apical foramina, accessory canals, and dentinal tubules. Due to this interrelationship, pulpal diseases may influence periodontal health and periodontal infections may affect pulpal integrity. It is estimated that pulpal and periodontal problems are responsible for more than 50% of tooth mortality. Thus, these associations recommend an interdisciplinary approach. MTA appears to exhibit significant results even in periodontal procedures as it is the first restorative material that consistently allows for over-growth of cementum and may facilitate periodontal tissue regeneration. Thus, in the present review, an attempt is made to discuss the clinical applications of MTA as an interdisciplinary approach. PMID:24744536

  3. Mineral trioxide aggregate apexification: A novel approach

    PubMed Central

    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

  4. Mineral trioxide aggregate apexification: A novel approach.

    PubMed

    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

  5. The chemical composition of mineral trioxide aggregate

    PubMed Central

    Camilleri, Josette

    2008-01-01

    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. PMID:20351970

  6. Speciation of arsenic oxides using laser desorption/ionization time-of-flight mass spectrometry.

    PubMed

    Allen, T M; Bezabeh, D Z; Smith, C H; McCauley, E M; Jones, A D; Chang, D P; Kennedy, I M; Kelly, P B

    1996-11-15

    Positive and negative ion mass spectra of arsenic trioxide (As2O3) and arsenic pentaoxide (As2O5) have been obtained by single-step laser desorption/ionization time-of-flight mass spectrometry. Pulsed UV radiation at 266 nm was used for the simultaneous desorption and ionization of the solid sample. High-mass cluster ions that are unique to the oxidation state of each oxide sample appear in the negative ion mass spectra. The As2O3 produces As3O5-, while the As2O5 yields As3O8-. The formation of unique negative cluster ions presents the capability for arsenic oxidation state speciation by laser desorption/ionization mass spectrometry. The ability of time-of-flight mass spectrometry to examine the relative amounts of each arsenic oxide present in a series of mixtures is discussed. Application of our speciation technique to a model incinerator sample is demonstrated. PMID:8916457

  7. An Aerosol Condensation Model for Sulfur Trioxide

    SciTech Connect

    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. Arsenic surveillance program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background information about arsenic is presented including forms, common sources, and clinical symptoms of arsenic exposure. The purpose of the Arsenic Surveillance Program and LeRC is outlined, and the specifics of the Medical Surveillance Program for Arsenic Exposure at LeRC are discussed.

  9. Earth Abides Arsenic Biotransformations

    PubMed Central

    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

  10. Earth Abides Arsenic Biotransformations

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:9644328

  12. Understanding the Oxygen Vacancy in Tungsten Trioxide

    NASA Astrophysics Data System (ADS)

    Wang, Wennie; Janotti, Anderson; van de Walle, Chris G.

    2015-03-01

    Tungsten trioxide (WO3) has a variety of applications in gas sensors, photocatalysis, and smart windows. As an electrochromic BO3 perovskite, WO3 turns from transparent to blue upon doping. This color change is correlated with a drop in transmittance of near-IR radiation, and is used in smart windows for energy efficiency. In addition to monovalent species doping that modulates optical properties, oxygen deficiencies have been found to have a similar electrochromic effect. The influence of oxygen vacancies on electronic structure and how it corresponds to electrochromic behavior remains a topic of debate. In this work, we examine the oxygen vacancy in monoclinic WO3 and its influence on electronic structure using density functional theory with a hybrid functional. We investigate the relative stability of different charge states and its implications for electrical properties, such as conductivity and electrochromism. We find oxygen vacancies to be shallow donors, and explore similarities and differences with monovalent species doping. Finally, we compare our theoretical findings with experiment to elucidate how vacancies may contribute to electrochromic behavior. This work is supported by DOE and NSF.

  13. THE CELLUAR METABOLISM OF ARSENIC

    EPA Science Inventory

    Because the methylation of arsenic produces intermediates and terminal products that exceed inorganic arsenic in potency as enzyme inhibitors, cytotoxins, and genotoxins, the methylation of arsenic is properly regarded as an activation process. The methylation of arsenic is an e...

  14. Chem I Supplement: Arsenic and Old Myths.

    ERIC Educational Resources Information Center

    Sarquis, Mickey

    1979-01-01

    Describes the history of arsenic, the properties of arsenic, production and uses of arsenicals, arsenic in the environment; toxic levels of arsenic, arsenic in the human body, and the Marsh Test. (BT)

  15. Prophylactic treatment of dens evaginatus using mineral trioxide aggregate.

    PubMed

    Koh, E T; Ford, T R; Kariyawasam, S P; Chen, N N; Torabinejad, M

    2001-08-01

    Two case reports with dens evaginatus are presented. Each patient had one tooth affected. There was a prominent tubercle on the occlusal surface of the mandibular second premolar. Under local anesthesia and rubber dam isolation a partial pulpotomy was conducted and mineral trioxide aggregate was placed. After 6 months the teeth were removed as part of planned orthodontic treatment. Histological examination of these teeth showed an apparent continuous dentin bridge formation in both teeth, and the pulps were free of inflammation. These cases show that mineral trioxide aggregate can be used as an alternative to existing materials in the proplylactic treatment of dens evaginatus. PMID:11501594

  16. Massive acute arsenic poisonings.

    PubMed

    Lech, Teresa; Trela, Franciszek

    2005-07-16

    Arsenic poisonings are still important in the field of toxicology, though they are not as frequent as about 20-30 years ago. In this paper, the arsenic concentrations in ante- and post-mortem materials, and also forensic and anatomo-pathological aspects in three cases of massive acute poisoning with arsenic(III) oxide (two of them with unexplained criminalistic background, in which arsenic was taken for amphetamine and one suicide), are presented. Ante-mortem blood and urine arsenic concentrations ranged from 2.3 to 6.7 microg/ml, respectively. Post-mortem tissue total arsenic concentrations were also detected in large concentrations. In case 3, the contents of the duodenum contained as much as 30.1% arsenic(III) oxide. The high concentrations of arsenic detected in blood and tissues in all presented cases are particularly noteworthy in that they are very rarely detected at these concentrations in fatal arsenic poisonings. PMID:15939162

  17. Arsenite as the probable active species in the human carcinogenicity of arsenic: Mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution

    SciTech Connect

    Tinwell, H.; Ashby, J. ); Stephens, S.C. )

    1991-11-01

    Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay ({approximately} 10 mg/kg by IP injection). The natural ore orpiment (principally As{sub 2}S{sub 3}) was inactive despite blood levels of arsenic of 300 to 900 mg/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the skin cancer among people exposed therapeutically to Fowler's solution, have, as their common origin, the genotoxic arsenite ion AsO{sub 2}{sup {minus}}. The difficulty experienced when attempting to demonstrate rodent carcinogenicity for derivatives of arsenic suggests that the bone marrow micronucleus assay may act as a useful assay for potentially carcinogenic arsenic derivatives.

  18. Arsenic and 17-β-estradiol bind to each other and neutralize each other's signaling effects.

    PubMed

    Kumar, Sukhdeep; Mukherjee, Tapan K; Guptasarma, Purnananda

    2016-09-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D (1)H and (13)C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl (1)H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. PMID:27346132

  19. Method for the reduction of sulfur trioxide in an effluent

    SciTech Connect

    Epperly, W.R.; Sullivan, J.C.; Sprague, B.N.

    1989-04-18

    A method is described for the selective reduction of sulfur trioxide in the effluent from the combustion of a carbonaceous fuel, the method comprising introducing a treatment agent comprising hydrogen peroxide or an oxygenated hydrocarbon having at least two carbon atoms into the effluent at an effluent temperature of between about 1000/sup 0/F and about 1450/sup 0/F.

  20. EMISSIONS OF SULFUR TRIOXIDE FROM COAL-FIRED POWER PLANTS

    EPA Science Inventory

    Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough not to cause opacity violations and acid deposition. Generally, a small fraction of sulfur in coal is converted to SO3 in coal-fired co...

  1. Toxic Substances Portal- Arsenic

    MedlinePlus

    ... industrial applications. Organic arsenic compounds are used as pesticides, primarily on cotton fields and orchards. top What ... as copper or lead smelting, wood treating, or pesticide application. top How can arsenic affect my health? ...

  2. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

    A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer. PMID:7023936

  3. Arsenic in Food

    MedlinePlus

    ... inorganic forms. The FDA has been measuring total arsenic concentrations in foods, including rice and juices, through its Total Diet Study program ... readily take up much arsenic from the ground, rice is different because it takes ... has high levels of less toxic organic arsenic. Do organic foods ...

  4. NEVADA ARSENIC STUDY

    EPA Science Inventory

    The effects of exposure to arsenic in U.S. drinking water at low levels are difficult to assess. In particular, studies of sufficient sample size on US populations exposed to arsenic in drinking water are few. Churchill County, NV (population 25000) has arsenic levels in drinki...

  5. ARSENIC REMOVAL TECHNOLOGY

    EPA Science Inventory

    Presentation will discuss the state-of-art technology for removal of arsenic from drinking water. Presentation includes results of several EPA field studies on removal of arsenic from existing arsenic removal plants and key results from several EPA sponsored research studies. T...

  6. ARSENIC SOURCES AND ASSESSMENT

    EPA Science Inventory

    Recent research has identified a number of potential and current links between environmental arsenic releases and the management of operational and abandoned landfills. Many landfills will receive an increasing arsenic load due to the disposal of arsenic-bearing solid residuals ...

  7. Robust Structure and Reactivity of Aqueous Arsenous Acid-Platinum(II) Anticancer Complexes**

    PubMed Central

    Miodragović, Ðenana U.; Quentzel, Jeremy A.; Kurutz, Josh W.; Stern, Charlotte L.; Ahn, Richard W.; Kandela, Irawati; Mazar, Andrew; O’Halloran, Thomas V.

    2014-01-01

    The first molecular adducts of platinum and arsenic based anticancer drugs - arsenoplatins - show unanticipated structure, substitution chemistry, and cellular cytotoxicity. The PtII-AsIII bonds in these complexes are stable in aqueous solution and strongly influence the lability of the trans ligand. PMID:24038962

  8. Arsenic pollution sources.

    PubMed

    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

  9. Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

    PubMed Central

    Huang, Chun-Fa; Yang, Ching-Yao; Chan, Ding-Cheng; Wang, Ching-Chia; Huang, Kuo-How; Wu, Chin-Ching; Tsai, Keh-Sung; Yang, Rong-Sen

    2015-01-01

    Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic

  10. Suppression of pancreatic tumor growth by targeted arsenic delivery with anti-CD44v6 single chain antibody conjugated nanoparticles.

    PubMed

    Qian, Chenchen; Wang, Yong; Chen, Yinting; Zeng, Linjuan; Zhang, Qiubo; Shuai, Xintao; Huang, Kaihong

    2013-08-01

    Arsenic trioxide (As2O3) is a promising anticancer agent for solid tumors. However, the high toxicity to normal tissues resulting from the lack of tumor specificity remains a huge challenge in its systemic application. Targeted vectors enabling drug delivery to specific cancer cells bring about great potential for better therapeutic efficacy whereas low side effects in cancer treatments. Our previous work has demonstrated that the anti-CD44v6 single chain variable fragment (scFv(CD44v6)) screened out from the human phage-displayed scFv library possesses high specificity and affinity to membrane antigen CD44v6 over-expressing in a subset of epithelium-derived cancers, such as pancreatic, hepatocellular, colorectal and gastric cancers. Herein, a maleimide-functionalized amphiphilic diblock copolymer of poly (ethylene glycol) and poly (D, L-lactide) (mal-PEG-PDLLA) was synthesized and assembled to vesicles with arsenite ion (As) encapsulated in their cores (As-NPs). Conjugation of scFv(CD44v6) with mal-PEG-PDLLA (scFv-As-NPs) enabled more efficient delivery of As and exhibited higher cytotoxic activity than non-targeted ones (As-NPs) in human pancreatic cancer cells PANC-1. Furthermore, the targeted delivery of As induced more significant gene suppression in terms of the expression of anti-apoptotic Bcl-2 protein. Consequently, the expression level of cleaved caspase-3 which is a molecular indicator of cell apoptosis was remarkably elevated. In animal tests, scFv-As-NPs were found to greatly increase accumulation of drug in tumor site and potentiate the efficacy of As in inhibiting tumor growth owing to the enhanced cell apoptosis. These results imply that our tumor specific nanocarriers provide a highly efficient and safe platform for pancreatic cancer therapy. PMID:23721794

  11. Construction of carbon nanodots/tungsten trioxide and their visible-light sensitive photocatalytic activity.

    PubMed

    Yan, Fanyong; Kong, Depeng; Fu, Yang; Ye, Qianghua; Wang, Yinyin; Chen, Li

    2016-03-15

    Herein we designed a simple and effective method for synthesizing carbon nanodots/tungsten trioxide nanocomposite with high photocatalytic activity. The as-prepared carbon nanodots/ tungsten trioxide has strong photoabsorption under visible light irradiation. Then, carbon nanodots/tungsten trioxide was successfully applied to the degradation of methylene blue. The photodegradation efficiency of methylene blue can be reached as high as 100% after 0.5 h visible light illumination. In addition, carbon nanodots/tungsten trioxide could also be used to degrade rhodamine B and methyl orange. Most importantly, the photocatalytic activity of carbon nanodots/tungsten trioxide did not exhibit obvious changes after five cycles. The results indicate that carbon nanodots/tungsten trioxide has potential applications in the degradation of organic pollutants in industrial waste water. PMID:26745743

  12. Arsenic-Based Antineoplastic Drugs and Their Mechanisms of Action

    PubMed Central

    Ralph, Stephen John

    2008-01-01

    Arsenic-based compounds have become accepted agents for cancer therapy providing high rates of remission of some cancers such as acute promyelocytic leukemia (APL). The mechanisms by which arsenic-containing compounds kill cells and reasons for selective killing of only certain types of cancer cells such as APLs have recently been delineated. This knowledge was gained in parallel with increasing understanding and awareness of the importance of intracellular redox systems and regulation of the production of reactive oxygen species (ROS) by controlling mitochondrial function. Many of the targets for the arsenic-containing compounds are mitochondrial proteins involved in regulating the production of ROS. Inhibition of these proteins by disulfide linkage of vicinal thiol groups often leads to increased production of ROS and induction of apoptotic signalling pathways. Sensitivity or resistance to the actions of arsenic-containing compounds on cancer cells and normal cells depends on the levels of transport systems for their uptake or efflux from the cells as well as their redox defence mechanisms. The exact mechanisms of arsenic toxicity as well as its anticancer properties are likely to be related and these aspects of arsenic metabolism are covered in this review. Greater understanding of the mechanisms of action of arsenic will help determine the risks of human exposure to this chemical. Novel organic arsenic-containing compounds and the lessons learned from studying their selective sensitivity in targeting dividing endothelial cells to inhibit angiogenesis raise the future possibility for designing better targeted antineoplastic arsenic-containing compounds with less toxicity to normal cells. PMID:18431449

  13. Arsenic removal from water

    DOEpatents

    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.

  14. Arsenic: homicidal intoxication

    SciTech Connect

    Massey, E.W.; Wold, D.; Heyman, A.

    1984-07-01

    Arsenic-induced deaths have been known to occur from accidental poisoning, as a result of medical therapy, and from intentional poisonings in homicide and suicide. Twenty-eight arsenic deaths in North Carolina from 1972 to 1982 included 14 homicides and seven suicides. In addition, 56 hospitalized victims of arsenic poisoning were identified at Duke Medical Center from 1970 to 1980. Four case histories of arsenic poisoning in North Carolina are presented and clinical manifestations are discussed. In view of the continued widespread use of arsenic in industry and agriculture, and its ubiquity in the environment, arsenic poisoning will continue to occur. A need for knowledge of its toxicity and of the clinical manifestations of acute and chronic arsenic poisoning will also continue.

  15. The Form, Distribution and Mobility of Arsenic in Soils Contaminated by Arsenic Trioxide, at Sites in Southeast USA

    SciTech Connect

    Yang,L.; Donahoe, R.

    2007-01-01

    Soils from many industrial sites in southeastern USA are contaminated with As because of the application of herbicide containing As{sub 2}O{sub 3}. Among those contaminated sites, two industrial sites, FW and BH, which are currently active and of most serious environmental concerns, were selected to characterize the occurrence of As in the contaminated soils and to evaluate its environmental leachability. The soils are both sandy loams with varying mineralogical and organic matter contents. Microwave-assisted acid digestion (EPA method 3051) of the contaminated soils indicated As levels of up to 325 mg/kg and 900 mg/kg (dry weight basis) for FW and BH soils, respectively. However, bulk X-ray powder diffraction (XRD) analysis failed to find any detectable As-bearing phases in either of the studied soil samples. Most of the soil As was observed by scanning electron microscopy, coupled with energy dispersive X-ray spectroscopy (SEM/EDX), to be disseminated on the surfaces of fine-grained soil particles in close association with Al and Fe. A few As-bearing particles were detected in BH soil using electron microprobe analysis (EMPA). Synchrotron micro-XRD and X-ray absorption near-edge structure (XANES) analyses indicated that these As-rich particles were possibly phaunouxite, a mineral similar to calcium arsenate, which could have been formed by natural weathering after the application of As{sub 2}O{sub 3}. However, the scarcity of those particles eliminated them from playing any important role in As sequestration. Synthetic acid rain sequential batch leaching experiments showed distinct As leaching behaviors of the two studied soil samples: BH soil, which has the higher As content, showed a slow, steady release of As, while FW soil, with a lower As content, showed a much quicker release and lower overall retention of As upon leaching. Sequential chemical extraction experiments were carried out using a simplified 4-step sequential chemical extraction procedure (SCEP) previously developed to characterize the fractionation of As and better understand the different leaching behaviors of the two studied soils. It was shown that only about 50% of the total extractable As was removed by the first two extraction steps, which represented the most weakly bonded and readily available As for environmental leaching. Compared with the sequential leaching experiments, it was further indicated that only half of the As associated with phases extracted by the second SCEP step was mobilized by SPLP leaching. Although microwave-assisted acid digestion results showed similar Al and Fe contents in both soils, the sequential chemical extraction experiments indicated that BH soil has a much higher content of amorphous Al and Fe phases and that a comparably higher portion of soil As was associated with those materials. The experimental results suggest that remediation efforts for the contaminated sites can be directed towards enhancing the formation of more stable As-bearing compounds in the soils to reduce the environmental leachability of As.

  16. The form, distribution and mobility of arsenic in soilscontaminated by arsenic trioxide, at sites in southeast USA

    SciTech Connect

    Yang, Li; Donahoe, Rona J.

    2005-03-04

    Soils from many industrial sites in southeastern USA arecontaminated with As because of the application of herbicide containingAs2O3. Among those contaminated sites, two industrial sites, FW and BH,which are currently active and of most serious environmental concerns,were selected to characterize the occurrence of As in the contaminatedsoils and to evaluate its environmental leachability. The soils are bothsandy loams with varying mineralogical and organic matter contents.Microwave-assisted acid digestion (EPA method 3051) of the contaminatedsoils indicated As levels of up to 325 mg/kg and 900 mg/kg (dry weightbasis) for FW and BH soils, respectively. However, bulk X-ray powderdiffraction (XRD) analysis failed to find any detectable As-bearingphases in either of the studied soil samples. Most of the soil As wasobserved by scanning electron microscopy, coupled with energy dispersiveX-ray spectroscopy (SEM/EDX), to be disseminated on the surfaces offine-grained soil particles in close association with Al and Fe. A fewAs-bearing particles were detected in BH soil using electron microprobeanalysis (EMPA). Synchrotron micro-XRD and X-ray absorption near-edgestructure (XANES) analyses indicated that these As-rich particles werepossibly phaunouxite, a mineral similar to calcium arsenate, which couldhave been formed by natural weathering after the application of As2O3.However, the scarcity of those particles eliminated them from playing anyimportant role in Assequestration.Synthetic acid rain sequential batchleaching experiments showed distinct As leaching behaviors of the twostudied soil samples: BH soil, which has the higher As content, showed aslow, steady release of As, while FW soil, with a lower As content,showed a much quicker release and lower overall retention of As uponleaching. Sequential chemical extraction experiments were carried outusing a simplified 4-step sequential chemical extraction procedure (SCEP)previously developed to characterize the fractionation of As and betterunderstand the different leaching behaviors of the two studied soils. Itwas shown that only about 50 percent of the total extractable As wasremoved by the first two extraction steps, which represented the mostweakly bonded and readily available As forenvironmental leaching.Compared with the sequential leaching experiments, it was furtherindicated that only half of the As associated with phases extracted bythe second SCEP step was mobilized by SPLP leaching. Althoughmicrowave-assisted acid digestion results showed similar Al and Fecontents in both soils, the sequential chemical extraction experimentsindicated that BH soil has a much higher content of amorphous Al and Fephases and that a comparably higher portion of soil As was associatedwith those materials. The experimental results suggest that remediationefforts for the contaminated sites can be directed towards enhancing theformation of more stable As-bearing compounds in the soils to reduce theenvironmental leachability of As.

  17. ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE METHYLATION OF ARSENICALS

    EPA Science Inventory

    Metabolic conversion of inorganic arsenic into methylated products is a multistep process that yields mono, di, and trimethylated arsenicals. In recent years, it has become apparent that formation of methylated metabolites of inorganic arsenic is not necessarily a detoxification...

  18. Production of sulfur trioxide, sulfuric acid and oleum

    SciTech Connect

    Daley, W.D.; Jaffe, J.

    1987-02-17

    A process is described for the production of sulfur trioxide which comprises the steps: (a) feeding a gas mixture having a sulfur dioxide partial pressure of at least about 0.5 atmosphere, an oxygen partial pressure of at least about 0.37 atmosphere, an oxygen:-sulfur dioxide mole ratio of between about 0.7:1 and about 1:1. It also has a total pressure between about 1 atmosphere and about 10 atmospheres in plug flow through a bed of a conversion catalyst selected from the group consisting of vanadium oxide conversion catalysts and platinum conversion catalysts; (b) cooling the catalyst bed to produce a first zone wherein the gas mixture increases in temperature from the inlet temperature to a temperature between about 475/sup 0/C. and about 575/sup 0/C., a second zone wherein the temperature is substantially constant at a temperature between about 450/sup 0/C. and about 575/sup 0/C. and a third zone wherein the temperature is declining from a temperature between about 450/sup 0/C. and about 575/sup 0/C. to a temperature between about 325/sup 0/C. and about 400/sup 0/C., (c) passing the gas mixture successively through the first, second and third zones with sufficient contact times in the second and third zones to produce a product gas mixture with a sulfur trioxide to sulfur dioxide mole ratio of at least about 99:1, (d) cooling the product gas mixture to a temperature between about 35/sup 0/C. and about 45/sup 0/C. to produce liquid sulfur trioxide, and (e) separating the liquid sulfur trioxide from the remaining gas stream.

  19. COMMONALITIES IN METABOLISM OF ARSENICALS

    EPA Science Inventory

    Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with e...

  20. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    PubMed Central

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  1. Response to Comment on "SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML".

    PubMed

    Fasci, Domenico; Anania, Veronica; Lill, Jennie; Salvesen, Guy

    2016-01-01

    Arsenic trioxide chemotherapy cures acute promyelocytic leukemia by inducing the ubiquitylation of an oncogenic fusion protein containing promyelocytic leukemia protein (PML) subsequent to modification of PML by SUMO1 and SUMO2. We proposed that the SUMO switch at Lys(65) of PML enhanced subsequent SUMO2 conjugation to Lys(160) and consequent RNF4-dependent ubiquitylation of PML. Ferhi et al note differences between their experimental system and ours regarding the outcome and mechanisms of SUMO-dependent PML signaling. When confronted by apparently contradictory data, it is appropriate to drill down to where the differences could lie. PMID:27507652

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

    PubMed Central

    Betti, Lucietta; Trebbi, Grazia; Borghini, Giovanni; Nani, Daniele; Dinelli, Giovanni

    2014-01-01

    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. PMID:25525452

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

    ClinicalTrials.gov

    2013-09-13

    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

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    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

  6. Arsenic trioxide inhibits glioma cell growth through induction of telomerase displacement and telomere dysfunction

    PubMed Central

    Cheng, Ye; Li, Yunqian; Ma, Chengyuan; Song, Yang; Xu, Haiyang; Yu, Hongquan; Xu, Songbai; Mu, Qingchun; Li, Haisong; Chen, Yong; Zhao, Gang

    2016-01-01

    Glioblastomas are resistant to many kinds of treatment, including chemotherapy, radiation and other adjuvant therapies. As2O3 reportedly induces ROS generation in cells, suggesting it may be able to induce telomerase suppression and telomere dysfunction in glioblastoma cells. We show here that As2O3 induces ROS generation as well as telomerase phosphorylation in U87, U251, SHG4 and C6 glioma cells. It also induces translocation of telomerase from the nucleus to the cytoplasm, thereby decreasing total telomerase activity. These effects of As2O3 trigger an extensive DNA damage response at the telomere, which includes up-regulation of ATM, ATR, 53BP1, γ-H2AX and Mer11, in parallel with telomere fusion and 3′-overhang degradation. This ultimately results in induction of p53- and p21-mediated cell apoptosis, G2/M cell cycle arrest and cellular senescence. These results provide new insight into the antitumor effects of As2O3 and can perhaps contribute to solving the problem of glioblastoma treatment resistance. PMID:26871293

  7. 78 FR 59679 - Antimony Trioxide TSCA Chemical Risk Assessment; Notice of Public Meetings and Opportunity To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... AGENCY Antimony Trioxide TSCA Chemical Risk Assessment; Notice of Public Meetings and Opportunity To... review of EPA's draft Toxic Substances Control Act (TSCA) chemical risk assessment, ``TSCA Workplan Chemical Risk Assessment for Antimony Trioxide.'' EPA will hold three peer review meetings by web...

  8. Anticancer activity of ferrocenylthiosemicarbazones.

    PubMed

    Sandra, Cortez-Maya; Elena, Klimova; Marcos, Flores-Alamo; Elena, Martínez-Klimova; Arturo, Ramírez-Ramírez; Teresa, Ramírez Apan; Marcos, Martínez-García

    2014-03-01

    Aliphatic and aromatic ferrocenylthiosemicarbazones were synthesized. The characterization of the new ferrocenylthiosemicarbazones was done by IR, (1)H-NMR and (13)C-NMR spectroscopy, elemental analysis and X-ray diffraction studies. The biological activity of the obtained compounds was assessed in terms of anticancer activity. Their activity against U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma), K562 (human chronic myelogenous leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma) and SKLU-1 (human lung adenocarcinoma) cell lines was studied and compared with cisplatin. All tested compounds showed good activity and the aryl-chloro substituted ferrocenylthiosemicarbazones showed the best anticancer activity. PMID:24144199

  9. Kinetics of sulfonation of amines of the benzene series with sulfur trioxide

    SciTech Connect

    Khelevin, R.N.

    1988-08-20

    The sulfonation of amines of the benzene series with sulfur trioxide in dichloroethane is described by a third-order kinetic equation for an irreversible process, and first order is observed with respect to the compound being sulfonated and second with respect to the sulfur trioxide. The unprotonated molecules of the amines undergo sulfonation, and this leads to the production of the para-aminosulfonic acids with small amounts of the ortho isomers. The reaction mechanism involves electrophilic reaction of the unprotonated amine molecule with the sulfur trioxide dimer S/sub 2/O/sub 6/ and subsequent dissociation of the obtained pyrosulfonate with the production of the amino sulfonic acid and sulfur trioxide. Sulfonation with sulfur trioxide is of interest in connection with the high rate and degree of completion of the reaction and the absence of energy expenditures.

  10. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    The biotransformation of inorganic arsenic (iAs) involves methylation by an arsenic (+3 oxidation state) methyltransferase (AS3MT), yielding methyl arsenic (MA), dimethyl arsenic (DMA), and trimethylarsenic (TMA). To identify molecular mechanisms that coordinate arsenic biotra...

  11. Anticancer drugs during pregnancy.

    PubMed

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. PMID:27284093

  12. Arsenic (Environmental Health Student Portal)

    MedlinePlus

    ... Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Arsenic The Basics Arsenic is an element that exists naturally in the Earth’s crust. Small amounts of arsenic are found in some rock, soil, water, and air. When arsenic combines with ...

  13. ARSENIC REMOVAL USING ADSORPTION TECHNOLOGIES

    EPA Science Inventory

    The recently promulgated Arsenic Rule will require that many new drinking water systems treat their water to remove arsenic. Many groundwaters that have arsenic in their source water will likely consider adsorption technology as a reasonable approach to remove arsenic. Adsorptio...

  14. ADSORPTION TECHNOLOGIES FOR ARSENIC REMOVAL

    EPA Science Inventory

    The recently promulgated Arsenic Rule will require that many new drinking water systems treat their water to remove arsenic. Many groundwaters that have arsenic in their source water will likely consider adsorption technology as a reasonable approach to remove arsenic. Adsorptio...

  15. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  16. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  17. ARSENIC AND OHIO UTILITIES

    EPA Science Inventory

    The presentation provides information on arsenic removal drinking water treatment systems that are likely to be used in Ohio for arsenic removal. Because most Ohio ground water contain significant amounts of iron, iron removal processes will play a major role in treating Ohio gro...

  18. An update on arsenic

    SciTech Connect

    Malachowski, M.E. )

    1990-09-01

    Arsenic poisoning is more than just a medical curiosity. Cases of acute and chronic intoxication continue to occur in the United States. Much is now known about the biochemical mechanisms of injury, which has led to a rational basis for therapy. Most importantly, however, the clinician must stay alert to correctly diagnose and treat cases of arsenic poisoning.23 references.

  19. Raman study of thermochromic phase transition in tungsten trioxide nanowires

    NASA Astrophysics Data System (ADS)

    Lu, Dong Yu; Chen, Jian; Chen, Huan Jun; Gong, Li; Deng, Shao Zhi; Xu, Ning Sheng; Liu, Yu Long

    2007-01-01

    Tungsten trioxide (WO3) nanowires were synthesized by thermal evaporation of tungsten powder in two steps: tungsten suboxide (WO3-x) nanowires were synthesized, and then oxidized in O2 ambient and transformed into WO3 nanowires. Raman spectroscopy was applied to study the thermochromic phase transition of one-dimensional WO3 nanowires. From the temperature dependence of the characteristic mode at 33cm-1 in WO3, the phase transition temperature was determined. It was found that the phase transition of WO3 nanowires was reversible and the phase transition temperatures were even lower than that of WO3 nanopowder.

  20. Acute arsenic intoxication from environmental arsenic exposure

    SciTech Connect

    Franzblau, A.; Lilis, R. )

    1989-11-01

    Reports of acute arsenic poisoning arising from environmental exposure are rare. Two cases of acute arsenic intoxication resulting from ingestion of contaminated well water are described. These patients experienced a variety of problems: acute gastrointestinal symptoms, central and peripheral neurotoxicity, bone marrow suppression, hepatic toxicity, and mild mucous membrane and cutaneous changes. Although located adjacent to an abandoned mine, the well water had been tested for microorganisms only and was found to be safe. Regulations for testing of water from private wells for fitness to drink are frequently nonexistent, or only mandate biologic tests for microorganisms. Well water, particularly in areas near mining activity, should be tested for metals.

  1. SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML

    PubMed Central

    Fasci, Domenico; Anania, Veronica G.; Lill, Jennie R.; Salvesen, Guy S.

    2015-01-01

    Acute promyelocytic leukemia is characterized by a chromosomal translocation that produces an oncogenic fusion protein of the retinoic acid receptor α (RARα) and promyelocytic leukemia protein (PML). Arsenic trioxide chemotherapy of this cancer induces the PML moiety to organize nuclear bodies, where the oncoprotein is degraded. This process requires the participation of two SUMO paralogs (SUMO1 and SUMO2) to promote PML ubiquitylation mediated by the ubiquitin E3 ligase RNF4 and reorganization of PML nuclear bodies. We demonstrated that the ubiquitylation of PML required the SUMO deconjugation machinery, primarily the deconjugating enzyme SENP1, and was suppressed by expression of non-deconjugatable SUMO2. We hypothesized that constitutive SUMO2 conjugation and deconjugation occurred basally, and that arsenic trioxide treatment caused the exchange of SUMO2 for SUMO1 on a fraction of Lys65 in PML. Based on data obtained with mutational analysis and quantitative proteomics, we propose that the SUMO switch at Lys65 of PML enhanced nuclear body formation, subsequent SUMO2 conjugation to Lys160, and consequent RNF4-dependent ubiquitylation of PML. Our work provides insights into how the SUMO system achieves selective SUMO paralog modification, and highlights the crucial role of SENPs in defining the specificity of SUMO signaling. PMID:26060329

  2. SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML.

    PubMed

    Fasci, Domenico; Anania, Veronica G; Lill, Jennie R; Salvesen, Guy S

    2015-06-01

    Acute promyelocytic leukemia is characterized by a chromosomal translocation that produces an oncogenic fusion protein of the retinoic acid receptor α (RARα) and promyelocytic leukemia protein (PML). Arsenic trioxide chemotherapy of this cancer induces the PML moiety to organize nuclear bodies, where the oncoprotein is degraded. This process requires the participation of two SUMO paralogs (SUMO1 and SUMO2) to promote PML ubiquitylation mediated by the ubiquitin E3 ligase RNF4 and reorganization of PML nuclear bodies. We demonstrated that the ubiquitylation of PML required the SUMO deconjugation machinery, primarily the deconjugating enzyme SENP1, and was suppressed by expression of non-deconjugatable SUMO2. We hypothesized that constitutive SUMO2 conjugation and deconjugation occurred basally and that arsenic trioxide treatment caused the exchange of SUMO2 for SUMO1 on a fraction of Lys(65) in PML. On the basis of data obtained with mutational analysis and quantitative proteomics, we propose that the SUMO switch at Lys(65) of PML enhanced nuclear body formation, subsequent SUMO2 conjugation to Lys(160), and consequent RNF4-dependent ubiquitylation of PML. Our work provides insights into how the SUMO system achieves selective SUMO paralog modification and highlights the crucial role of SENPs in defining the specificity of SUMO signaling. PMID:26060329

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

    PubMed Central

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

    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 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. PMID:22690182

  4. LincRNAs and base modifications of p53 induced by arsenic methylation in workers.

    PubMed

    Wen, Weihua; Lu, Lin; He, Yuefeng; Cheng, Huirong; He, Fang; Cao, Shuqiao; Li, Liang; Xiong, Li; Wu, Tangchun

    2016-02-25

    Arsenic (As) metabolites could induce methylation changes of DNA and base modifications of p53, which play role in the toxicity of As. LincRNAs should play a key regulatory role in the p53 transcriptional response. There were 43 workers producing As trioxide, 36 workers who stopped exposure to As trioxide about 85 days ago, and 24 individuals as control group. Three As species in urine were measured, and primary and secondary methylation indexes, iAs%, MMA% and DMA% were calculated. RT-PCR was performed to detect the expression of 7 LincRNAs and the base modifications of exon 5, 6, 7, and 8 of p53. The concentrations of urinary As were high in workers. Compared to control group, significant changes for 5 LincRNAs in workers producing As trioxide were found (P < 0.05), and there were significant base modifications of p53 in workers came from the two plants (P < 0.05). There exist various correlations between different exon base modifications of p53 and expressions of LincRNAs (P < 0.05). The closely positive correlations between MMA/DMA and MEG3/TUG1/HOTAIR/MALAT1 were found, but negative correlation between DMA/MALAT1 and the base modifications of exon 7 and 8 of p53 were found also (P < 0.05). LincRNAs and base modifications of p53 could be induced by As, MALAT1 and the base modifications of exon 7 and 8 of p53 could play unique roles in epigenic changes. These findings suggest potentially widespread roles of p53 and relative RNAs in arsenic workers, which may be caused by As metabolism. PMID:26772154

  5. Environmental biochemistry of arsenic

    SciTech Connect

    Tamaki, S.; Frankenberger, W.T. Jr. )

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  6. Anticancer properties of lamellarins.

    PubMed

    Bailly, Christian

    2015-03-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  7. Anticancer Properties of Lamellarins

    PubMed Central

    Bailly, Christian

    2015-01-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  8. Sesterterpenoids with Anticancer Activity.

    PubMed

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2015-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  9. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  10. Water hyacinth removes arsenic from arsenic-contaminated drinking water.

    PubMed

    Misbahuddin, Mir; Fariduddin, Atm

    2002-01-01

    Water hyacinth (Eichhornia crassipes) removes arsenic from arsenic-contaminated drinking water. This effect depends on several factors, such as the amount of water hyacinth, amount of arsenic present in the water, duration of exposure, and presence of sunlight and air. On the basis of the present study, the authors suggest that water hyacinth is useful for making arsenic-contaminated drinking water totally arsenic free. Water hyacinth provides a natural means of removing arsenic from drinking water at the household level without monetary cost. PMID:12696647

  11. High pseudotumor cerebri incidence in tretinoin and arsenic treated acute promyelocytic leukemia and the role of topiramate after acetazolamide failure

    PubMed Central

    Smith, Morgan B.; Griffiths, Elizabeth A.; Thompson, James E.; Wang, Eunice S.; Wetzler, Meir; Freyer, Craig W.

    2014-01-01

    Dual differentiation therapy with arsenic trioxide and tretinoin (all-trans-retinoic acid; ATRA) for the management of low and intermediate risk acute promyelocytic leukemia has recently been recommended by the National Comprehensive Cancer Network. Some less common toxicities of the combination may have yet to be fully realized. Of ten patients we have treated thus far, five (50%) have developed pseudotumor cerebri. In one patient, temporary discontinuation of ATRA and initiation of acetazolamide controlled symptoms. In four patients, topiramate was substituted for acetazolamide to relieve symptoms and allow ATRA dose re-escalation. We conclude that providers should monitor for pseudotumor cerebri and consider topiramate if acetazolamide fails. PMID:25180154

  12. USEPA Arsenic Demonstration Program

    EPA Science Inventory

    The presentation provides background information on the USEPA arsenic removal program. The summary includes information on the history of the program, sites and technology selected, and a summary of the data collected from two completed projects.

  13. ENZYMOLOGY OF ARSENIC METHYLATION

    EPA Science Inventory

    Enzymology of Arsenic Methylation

    David 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...

  14. Reaction of arsenic vapor species with fly ash compounds: kinetics and speciation of the reaction with calcium silicates.

    PubMed

    Sterling, R O; Helble, J J

    2003-06-01

    In coal combustion systems, the partitioning of arsenic between the vapor and solid phases is determined by the interaction of arsenic vapors with fly ash compounds under post-combustion conditions. This partitioning is affected by gas-solid reactions between the calcium components of the ash particles and arsenic vapors. In this study, bench scale experiments were conducted with calcium compounds typical of coal-derived fly ash to determine product formation, the extent of reaction and reaction rates when contacted by arsenic oxide vapors. Experiments conducted with arsenic trioxide (As(4)O(6(g))) vapors in contact with calcium oxide, di-calcium silicate and mono-calcium silicate over the temperature range 600-1000 degrees C indicated that these solids were capable of reacting with arsenic vapor species in both air and nitrogen. Calcium arsenate was the observed reaction product in all the samples analyzed. Maximum capture of arsenic occurred at 1000 degrees C with calcium oxide being the most effective of the three solids over the range of temperatures studied. Using a shrinking core model for a first order reaction and the results from intrinsic kinetic experiments conducted in air, the reaction rate constants were found to be 1.4 x 10(-3)exp(-2776/T) m/s for calcium oxide particles, 7.2 x 10(-3)exp(-3367/T) m/s for di-calcium silicate particles and 5.5 x 10(-3)exp(-3607/T) m/s for mono-calcium silicate particles. These results therefore suggest that any calcium present in fly ash can react with arsenic vapor and capture the metal in water-insoluble forms of the less hazardous As(V) oxidation state. PMID:12718977

  15. Electrochromic properties of molybdenum trioxide thin films prepared by chemical vapor deposition

    SciTech Connect

    Maruyama, Toshiro; Kanagawa, Tetsuya

    1995-05-01

    Electrochromic molybdenum trioxide thin films were prepared by chemical vapor deposition. The source material was molybdenum carbonyl. Amorphous molybdenum trioxide thin films were produced at a substrate temperature 300 C. Reduction and oxidation of the films in a 0.3M LiClO{sub 4} propylene carbonate solution caused desirable changes in optical absorption. Coulometry indicated that the coloration efficiency was 25.8 cm{sup 2}/C.

  16. Mineral Trioxide Aggregate and Portland Cement for Direct Pulp Capping in Dog: A Histopathological Evaluation

    PubMed Central

    Bidar, Maryam; Naghavi, Neda; Mohtasham, Nooshin; Sheik-Nezami, Mahshid; Fallahrastegar, Amir; Afkhami, Farzaneh; Attaran Mashhadi, Negin; Nargesi, Iman

    2014-01-01

    Background and aims. Mineral trioxide aggregate and calcium hydroxide are considered the gold standard pulp-capping materials. Recently, Portland cement has been introduced with properties similar to those of mineral trioxide aggregate. Histopathological effects of direct pulp capping using mineral trioxide aggregate and Portland cements on dog dental pulp tissue were evaluated in the present study. Materials and methods. This histopatological study was carried out on 64 dog premolars. First, the pulp was exposed with a sterile bur. Then, the exposed pulp was capped with white or gray mineral trioxide aggregates and white or gray Portland cements in each quadrant and sealed with glass-ionomer. The specimens were evaluated under a light microscope after 6 months. Statistical analysis was carried out using Kruskal-Wallis test. Statistical significance was defined at α=5%. Results. There was no acute inflammation in any of the specimens. Chronic inflammation in white and gray mineral trioxide aggregates and white and gray Portland cements was reported to be 45.5%, 27.3%, 57.1% and 34.1%, respectively. Although the differences were not statistically significant, severe inflammation was observed mostly adjacent to white mineral trioxide aggregate. The largest extent of increased vascularization (45%) and the least increase in fibrous tissue were observed adjacent to white mineral trioxide aggregate, with no significant differences. In addition, the least calcified tissue formed adjacent to white mineral trioxide aggregate, although the difference was not significant. Conclusion. The materials used in this study were equally effective as pulp protection materials following direct pulp capping in dog teeth. PMID:25346831

  17. Airborne arsenic exposure and excretion of methylated arsenic compounds.

    PubMed Central

    Smith, T J; Crecelius, E A; Reading, J C

    1977-01-01

    First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylarsinic acid) in these samples were analyzed by selective volatilization as arsines with determination of arsenic by plasma excitation emission spectrometry. On the day preceding the urine sample collection a breathing zone measurement was made of respirable arsenic particulates for each subject. It was found that all of the subjects, including the controls excreted arsenic primarily as methylated species. Approximately 50% of the total arsenic was excreted as dimethylarsinic acid and 20% as methylarsonic acid. Slight differences in the proportion of various arsenic compounds were observed with varying levels of inorganic arsenic exposure. Amounts of arsenic species were all closely correlated with each other and with exposure. Irrespirable particulate exposures were measured on a subset of high exposure workers. Irrespirable arsenic was found to be more closely correlated with excretion of arsenic compounds than was respirable arsenic. PMID:908318

  18. Electrochromism of electrodeposited tungsten trioxide films; 1: Electrochemical characterization

    SciTech Connect

    Shen, P.K.; Chen, K.Y.; Tseung, A.C.C. . Dept. of Chemistry and Biological Chemistry)

    1994-07-01

    Electrodeposited tungsten trioxide films show fast electrochromic response both in aqueous and in nonaqueous solutions. The values of x in the tungsten bronzes, M[sub x]WO[sub 3], were determined by using a chronopotentiometric technique combined with UV/Vis spectroscopic analysis. The effect of double-layer charging was discussed. A finite diffusion control model was used to analyze the insertion behavior of M[sup +] ions into the films. The apparent diffusion coefficient of Li[sup +] through the electrodeposited WO[sub 3] film is about two orders of magnitude higher than that of vacuum-evaporated WO[sub 3] films, indicating that electrodeposited films are more suitable for use as display devices than vacuum-evaporated films. The higher porosity of the electrodeposited WO[sub 3] films may be a main reason for the fast electrochromic response.

  19. Chemical characteristics of mineral trioxide aggregate and its hydration reaction

    PubMed Central

    2012-01-01

    Mineral trioxide aggregate (MTA) was developed in early 1990s and has been successfully used for root perforation repair, root end filling, and one-visit apexification. MTA is composed mainly of tricalcium silicate and dicalcium silicate. When MTA is hydrated, calcium silicate hydrate (CSH) and calcium hydroxide is formed. Formed calcium hydroxide interacts with the phosphate ion in body fluid and form amorphous calcium phosphate (ACP) which finally transforms into calcium deficient hydroxyapatite (CDHA). These mineral precipitate were reported to form the MTA-dentin interfacial layer which enhances the sealing ability of MTA. Clinically, the use of zinc oxide euginol (ZOE) based materials may retard the setting of MTA. Also, the use of acids or contact with excessive blood should be avoided before complete set of MTA, because these conditions could adversely affect the hydration reaction of MTA. Further studies on the chemical nature of MTA hydration reaction are needed. PMID:23429542

  20. Microwave spectra and quadrupole coupling measurements for methyl rhenium trioxide

    NASA Astrophysics Data System (ADS)

    Sickafoose, S. M.; Wikrent, P.; Drouin, B. J.; Kukolich, S. G.

    1996-12-01

    Microwave rotational transitions for J' ← J = 1 ← 0 and 2 ← 1 were measured in the 6-14 GHz range for methyl rhenium trioxide using a Flygare-Balle type, pulsed-beam spectrometer. The rotational constants for the most abundant isotopomers are B( 187Re) = 3466.964(2) MHz and B( 185Re) = 3467.049(3) MHz. The quadrupole coupling strengths are eQq( 187Re) = 716.55(2) MHz and eQq( 185Re) = 757.19(3) MHz. Transitions were also observed for 13C isotopomers and 18O isotopomers. The value for the ReC bond length obtained from a Kraitchman analysis is R( ReC) = 2.080 Å. The rhenium quadrupole coupling strengths are about 20% smaller than those obtained for HRe(CO) 5.

  1. Clinical Applications of Mineral Trioxide Aggregate: Report of Four Cases

    PubMed Central

    Battepati, Prashant M

    2010-01-01

    The greatest threats to developing teeth are dental caries and traumatic injuries. The primary goal of all restorative treatment is to maintain pulp vitality so that normal root development or apexogenesis can occur. If pulpal exposure occurs, then a pulpotomy procedure aims to preserve pulp vitality to allow for normal root development. Historically, calcium hydroxide has been the material of choice for pulpotomy procedures. Recently, an alternative material called mineral trioxide aggregate (MTA) has demonstrated the ability to induce hard-tissue formation in pulpal tissue. This article describes the clinical and radiographic outcome of a series of cases involving the use of MTA in pulpotomy, apexogenesis and apexification procedures and root perforations repair.

  2. Chemical characteristics of mineral trioxide aggregate and its hydration reaction.

    PubMed

    Chang, Seok-Woo

    2012-11-01

    Mineral trioxide aggregate (MTA) was developed in early 1990s and has been successfully used for root perforation repair, root end filling, and one-visit apexification. MTA is composed mainly of tricalcium silicate and dicalcium silicate. When MTA is hydrated, calcium silicate hydrate (CSH) and calcium hydroxide is formed. Formed calcium hydroxide interacts with the phosphate ion in body fluid and form amorphous calcium phosphate (ACP) which finally transforms into calcium deficient hydroxyapatite (CDHA). These mineral precipitate were reported to form the MTA-dentin interfacial layer which enhances the sealing ability of MTA. Clinically, the use of zinc oxide euginol (ZOE) based materials may retard the setting of MTA. Also, the use of acids or contact with excessive blood should be avoided before complete set of MTA, because these conditions could adversely affect the hydration reaction of MTA. Further studies on the chemical nature of MTA hydration reaction are needed. PMID:23429542

  3. Mineral trioxide aggregate: part 2 - a review of the material aspects.

    PubMed

    Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

    2013-03-01

    The purpose of this two-part series is to review the composition, properties, and products of mineral trioxide aggregate (MTA) materials. PubMed and MedLine electronic databases were used to identify scientific papers from January 1991 to May 2010. Based on the selected inclusion criteria, citations were referenced from the scientific peer-reviewed dental literature. Mineral trioxide aggregate is a refined form of the parent compound, Portland cement (PC), and demonstrates a strong biocompatibility due to the high pH level and the material's ability to form hydroxyapatite. Mineral trioxide aggregate materials provide better microleakage protection than traditional endodontic materials as observed in findings from dye-leakage, fluid-filtration, protein-leakage, and bacterial penetration-leakage studies and has been recognized as a bioactive material. Various MTA commercial products are available, including gray mineral trioxide aggregate (GMTA), white mineral trioxide aggregate (WMTA), and mineral trioxide aggregate-Angelus (AMTA). Although these materials are indicated for various dental uses and applications, long-term in-vivo clinical studies are needed. Part 1 of this article highlighted and discussed the composition and characteristics of the material. Part 2 provides an overview of commercially available MTA materials. PMID:23631637

  4. Melatonin Anticancer Effects: Review

    PubMed Central

    Di Bella, Giuseppe; Mascia, Fabrizio; Gualano, Luciano; Di Bella, Luigi

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases. PMID:23348932

  5. ARSENIC URINARY METABOLITES: BIOMARKER STUDY

    EPA Science Inventory

    A population of adults and children with ranges of 10 to 300 g/l of arsenic in their drinking water will have their urine analyzed for total and speciated arsenic. A sample of 30 families will be selected based on tap water analyses for arsenic. This sample will comprise 50% adul...

  6. PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC

    EPA Science Inventory

    PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC.

    Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. In contrast,
    there is no accepted experimental animal model of inorganic arsenic carcinogenesis.
    Proposed mechanisms/modes of action for a...

  7. ADSORPTION MEDIA FOR ARSENIC REMOVAL

    EPA Science Inventory

    Presentation will discuss the use of adsorptive media for the removal of arsenic from drinking water. Presentation is a fundamental discussion on the use of adsorptive media for arsenic removal and includes information from several EPA field studies on removal of arsenic from dr...

  8. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt), yielding mono- , di- , and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation,...

  9. Arsenic, Anaerobes, and Astrobiology

    NASA Astrophysics Data System (ADS)

    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

  10. Arsenic-mediated nephrotoxicity.

    PubMed

    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. PMID:25703706

  11. Arsenic: The Silent Killer

    SciTech Connect

    Foster, Andrea

    2006-02-28

    Andrea Foster uses x-rays to determine the forms of potentially toxic elements in environmentally-important matrices such as water, sediments, plants, and microorganisms. In this free public lecture, Foster will discuss her research on arsenic, which is called the silent killer because dissolved in water, it is colorless, odorless, and tasteless, yet consumption of relatively small doses of this element in its most toxic forms can cause rapid and violent death. Arsenic is a well-known poison, and has been used as such since ancient times. Less well known is the fact that much lower doses of the element, consumed over years, can lead to a variety of skin and internal cancers that can also be fatal. Currently, what has been called the largest mass poisoning in history is occurring in Bangladesh, where most people are by necessity drinking ground water that is contaminated with arsenic far in excess of the maximum amounts determined to be safe by the World Health Organization. This presentation will review the long and complicated history with arsenic, describe how x-rays have helped explain the high yet spatially variable arsenic concentrations in Bangladesh, discuss the ways in which land use in Bangladesh may be exacerbating the problem, and summarize the impact of this silent killer on drinking water systems worldwide.

  12. Arsenics as bioenergetic substrates.

    PubMed

    van Lis, Robert; Nitschke, Wolfgang; Duval, Simon; Schoepp-Cothenet, Barbara

    2013-02-01

    Although at low concentrations, arsenic commonly occurs naturally as a local geological constituent. Whereas both arsenate and arsenite are strongly toxic to life, a number of prokaryotes use these compounds as electron acceptors or donors, respectively, for bioenergetic purposes via respiratory arsenate reductase, arsenite oxidase and alternative arsenite oxidase. The recent burst in discovered arsenite oxidizing and arsenate respiring microbes suggests the arsenic bioenergetic metabolisms to be anything but exotic. The first goal of the present review is to bring to light the widespread distribution and diversity of these metabolizing pathways. The second goal is to present an evolutionary analysis of these diverse energetic pathways. Taking into account not only the available data on the arsenic metabolizing enzymes and their phylogenetical relatives but also the palaeogeochemical records, we propose a crucial role of arsenite oxidation via arsenite oxidase in primordial life. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems. PMID:22982475

  13. Anticancer mechanisms of cannabinoids

    PubMed Central

    Velasco, G.; Sánchez, C.; Guzmán, M.

    2016-01-01

    In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy. Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents. PMID:27022311

  14. [Update on anticancer drugs].

    PubMed

    Roila, Fausto; Ballatori, Enzo

    2014-01-01

    Update on anticancer drugs. A thorough review of the clinical trials published over the last two years in major medical and oncological journals on a comprehensive spectrum of oncological conditions aims to provide at the same time (as the authors are well known representatives of the critical and complementary competences of clinical care and research methodology) an interesting double opportunity of update on: a) what is truly (i.e.documented and reliable) innovative and deserves adoption in daily care,vs what is either purely suggestive or clearly misleading; b) what are the methological, concrete, simple rules to observe in a field which is certainly moving fast, but at the same time generates highly controversial behaviors in research as well as in daily practices. The accompanying editorial (pag 60-63) further illustrates the way and the yield of using this material and approach both in the areas of nursing sciences and practice. PMID:25002061

  15. Microbiome and Anticancer Immunosurveillance.

    PubMed

    Zitvogel, Laurence; Ayyoub, Maha; Routy, Bertrand; Kroemer, Guido

    2016-04-01

    Anticancer immune responses can be considered a desirable form of autoimmunity that may be profoundly shaped by the microbiome. Here, we discuss evidence for the microbiome's influence on anti-tumor immunosurveillance, including those that are indirect and can act at a distance, and we put forward hypotheses regarding mechanisms of how these effects are implemented. These may involve cross-reactivity between microbial and tumor antigens shaping T cell repertoires and/or microbial products stimulating pattern recognition receptors that influence the type and intensity of immune responses. Understanding how the microbiome impacts natural cancer immunosurveillance as well as treatment-induced immune responses will pave the way for more effective therapies and prophylactics. PMID:27058662

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

    PubMed Central

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    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 six 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. PMID:22521957

  17. Arsenic levels in Oregon waters.

    PubMed Central

    Stoner, J C; Whanger, P D; Weswig, P H

    1977-01-01

    The arsenic content of well water in certain areas of Oregon can range up to 30 to 40 times the U.S.P.H.S. Drinking Water Standard of 1962, where concentrations in excess of 50 ppb are grounds for rejection. The elevated arsenic levels in water are postulated to be due to volcanic deposits. Wells in central Lane County, Oregon, that are known to contain arsenic rich water are in an area underlain by a particular group of sedimentary and volcanic rocks, which geologists have named the Fischer formation. The arsenic levels in water from wells ranged from no detectable amounts to 2,000 ppb. In general the deeper wells contained higher arsenic water. The high arsenic waters are characterized by the small amounts of calcium and magnesium in relation to that of sodium, a high content of boron, and a high pH. Water from some hot springs in other areas of Oregon was found to range as high as 900 ppb arsenic. Arsenic blood levels ranged from 32 ppb for people living in areas where water is low in arsenic to 250 ppb for those living in areas where water is known to contain high levels of arsenic. Some health problems associated with consumption of arsenic-rich water are discussed. PMID:908291

  18. Environmental Source of Arsenic Exposure

    PubMed Central

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

    2014-01-01

    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. PMID:25284196

  19. Arsenic Speciation of Terrestrial Invertebrates

    SciTech Connect

    Moriarty, M.M.; Koch, I.; Gordon, R.A.; Reimer, K.J. ); )

    2009-07-01

    The distribution and chemical form (speciation) of arsenic in terrestrial food chains determines both the amount of arsenic available to higher organisms, and the toxicity of this metalloid in affected ecosystems. Invertebrates are part of complex terrestrial food webs. This paper provides arsenic concentrations and arsenic speciation profiles for eight orders of terrestrial invertebrates collected at three historical gold mine sites and one background site in Nova Scotia, Canada. Total arsenic concentrations, determined by inductively coupled plasma mass spectrometry (ICP-MS), were dependent upon the classification of invertebrate. Arsenic species were determined by high-performance liquid chromatography (HPLC) ICP-MS and X-ray absorption spectroscopy (XAS). Invertebrates were found by HPLC ICP-MS to contain predominantly arsenite and arsenate in methanol/water extracts, while XAS revealed that most arsenic is bound to sulfur in vivo. Examination of the spatial distribution of arsenic within an ant tissue highlighted the differences between exogenous and endogenous arsenic, as well as the extent to which arsenic is transformed upon ingestion. Similar arsenic speciation patterns for invertebrate groups were observed across sites. Trace amounts of arsenobetaine and arsenocholine were identified in slugs, ants, and spiders.

  20. ELUCIDATING THE PATHWAY FOR ARSENIC METHYLATION

    EPA Science Inventory

    Enzymatically-catalyzed methylation of arsenic is part of a metabolic pathway that converts inorganic arsenic into methylated products. Hence, in humans chronically exposed to inorganic arsenic, methyl and dimethyl arsenic account for most of the arsenic that is excreted in the ...

  1. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    EPA Science Inventory

    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. Arsenic doped zinc oxide

    SciTech Connect

    Volbers, N.; Lautenschlaeger, S.; Leichtweiss, T.; Laufer, A.; Graubner, S.; Meyer, B. K.; Potzger, K.; Zhou Shengqiang

    2008-06-15

    As-doping of zinc oxide has been approached by ion implantation and chemical vapor deposition. The effect of thermal annealing on the implanted samples has been investigated by using secondary ion mass spectrometry and Rutherford backscattering/channeling geometry. The crystal damage, the distribution of the arsenic, the diffusion of impurities, and the formation of secondary phases is discussed. For the thin films grown by vapor deposition, the composition has been determined with regard to the growth parameters. The bonding state of arsenic was investigated for both series of samples using x-ray photoelectron spectroscopy.

  3. Arsenic removal by coagulation

    SciTech Connect

    Scott, K.N.; Green, J.F.; Do, H.D.; McLean, S.J.

    1995-04-01

    This study evaluated the removal of naturally occurring arsenic in a full-scale (106-mgd) conventional treatment plant. When the source water was treated with 3--10 mg/L of ferric chloride or 6, 10, or 20 mg/L of alum, arsenic removal was 81--96% (ferric chloride) and 23--71% (alum). Metal concentrations in the sludge produced during this study were below the state`s current hazardous waste levels at all coagulant dosages. No operational difficulties were encountered.

  4. Arsenic and Selenium

    NASA Astrophysics Data System (ADS)

    Plant, J. A.; Kinniburgh, D. G.; Smedley, P. L.; Fordyce, F. M.; Klinck, B. A.

    2003-12-01

    Arsenic (As) and selenium (Se) have become increasingly important in environmental geochemistry because of their significance to human health. Their concentrations vary markedly in the environment, partly in relation to geology and partly as a result of human activity. Some of the contamination evident today probably dates back to the first settled civilizations which used metals.Arsenic is in group 15 of the periodic table (Table 1) and is usually described as a metalloid. It has only one stable isotope, 75As. It can exist in the -III, -I, 0, III, and V oxidation states (Table 2).

  5. ARSENIC REMOVAL TREATMENT OPTIONS FOR SINGLE FAMILY HOMES

    EPA Science Inventory

    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...

  6. Efficacy of arsenic filtration by Kanchan arsenic filter in Nepal.

    PubMed

    Singh, Anjana; Smith, Linda S; Shrestha, Shreekrishna; Maden, Narendra

    2014-09-01

    Groundwater arsenic contamination has caused a significant public health burden in lowland regions of Nepal. For arsenic mitigation purposes, the Kanchan Arsenic Filter (KAF) was developed and validated for use in 2003 after pilot studies showed its effectiveness in removing arsenic. However, its efficacy in field conditions operating for a long period has been scarcely observed. In this study, we observe the efficacy of KAFs running over 6 months in highly arsenic-affected households in Nawalparasi district. We assessed pair-wise arsenic concentrations of 62 randomly selected household tubewells before filtration and after filtration via KAFs. Of 62 tubewells, 41 had influent arsenic concentration exceeding the Nepal drinking water quality standard value (50 μg/L). Of the 41 tubewells having unsafe arsenic levels, KAFs reduced arsenic concentration to the safe level for only 22 tubewells, an efficacy of 54%. In conclusion, we did not find significantly high efficacy of KAFs in reducing unsafe influent arsenic level to the safe level under the in situ field conditions. PMID:25252363

  7. Cancer in Experimental Animals Exposed to Arsenic and Arsenic Compounds

    PubMed Central

    Tokar, Erik J.; Benbrahim-Tallaa, Lamia; Ward, Jerold M.; Lunn, Ruth; Sams, Reeder L.; Waalkes, Michael P.

    2011-01-01

    Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, like mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC 2009). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals. PMID:20812815

  8. Arsenic in cancer treatment: challenges for application of realgar nanoparticles (a minireview).

    PubMed

    Baláž, Peter; Sedlák, Ján

    2010-06-01

    While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment-As(2)S(3), realgar-As(4)S(4), and arsenolite-arsenic trioxide, As(2)O(3)) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. PMID:22069650

  9. Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles (A Minireview)

    PubMed Central

    Baláž, Peter; Sedlák, Ján

    2010-01-01

    While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment—As2S3, realgar—As4S4, and arsenolite—arsenic trioxide, As2O3) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. PMID:22069650

  10. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats.

    PubMed

    Patlolla, Anita K; Todorov, Todor I; Tchounwou, Paul B; van der Voet, Gijsbert; Centeno, Jose A

    2012-11-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. PMID:23175155

  11. ARSENIC TREATMENT OPTIONS

    EPA Science Inventory

    The PPT presentation will provide information on the drinking water treatment options for small utilities to remove arsenic from ground water. The discussion will include information on the EPA BAT listed processes and on some of the newer technologies, such as the iron based ad...

  12. Arsenic Content in American Wine.

    PubMed

    Wilson, Denise

    2015-10-01

    Recent studies that have investigated arsenic content in juice, rice, milk, broth (beef and chicken), and other foods have stimulated an interest in understanding how prevalent arsenic contamination is in the U.S. food and beverage supply. The study described here focused on quantifying arsenic levels in wine. A total of 65 representative wines from the top four wine-producing states in the U.S. were analyzed for arsenic content. All samples contained arsenic levels that exceeded the U.S. Environmental Protection Agency (U.S. EPA) exposure limit for drinking water of 10 parts per billion (ppb) and all samples contained inorganic arsenic. The average arsenic detected among all samples studied was 23.3 ppb. Lead, a common co-contaminant to arsenic, was detected in 58% of samples tested, but only 5% exceeded the U.S. EPA exposure limit for drinking water of 15 ppb. Arsenic levels in American wines exceeded those found in other studies involving water, bottled water, apple juice, apple juice blend, milk, rice syrup, and other beverages. When taken in the context of consumption patterns in the U.S., the pervasive presence of arsenic in wine can pose a potential health risk to regular adult wine drinkers. PMID:26591333

  13. Arsenic in shrimp from Kuwait

    SciTech Connect

    Bou-Olayan, A.H.; Al-Yakoob, S.; Al-Hossaini, M.

    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.

  14. Speciation of arsenic in urine following intravenous administration of arsthinol in mice.

    PubMed

    Ajana, Imane; Astier, Alain; Gibaud, Stéphane

    2010-09-01

    Recent investigations have shown that arsthinol, a trivalent organoarsenic compound (dithiarsolane), has been active in vitro on leukemia cell lines and offers a better therapeutic index than arsenic trioxide, as estimated by the ratio LD50/IC50. To complete our understanding of its urinary excretion, a sensitive method using liquid chromatography coupled with mass spectrometry (LC-MS) was used. Mice were injected intravenously with a single dose of arsthinol at 0.2 mmol/kg of body weight. The amount of total arsenic in tissues and body fluids was determined by a colorimetric method and urine metabolites were analyzed on a C18 Acclaim PepMap 100 A column by LC-MS. Our results showed that only three arsenic species (acetarsol, acetarsol oxide and arsthinol) were detected in the first 24-h urine. Overall, this study confirms that the hydrolysis of dithiarsolanes to arsenoxides (i.e. acetarsol oxide) can be followed by an oxidation in arsonic acids (i.e. acetarsol). All these compounds are excreted in the urine. PMID:21495268

  15. Liquid phase deposition synthesis of hexagonal molybdenum trioxide thin films

    SciTech Connect

    Deki, Shigehito; Beleke, Alexis Bienvenu; Kotani, Yuki; Mizuhata, Minoru

    2009-09-15

    Hexagonal molybdenum trioxide thin films with good crystallinity and high purity have been fabricated by the liquid phase deposition (LPD) technique using molybdic acid (H{sub 2}MoO{sub 4}) dissolved in 2.82% hydrofluoric acid (HF) and H{sub 3}BO{sub 3} as precursors. The crystal was found to belong to a hexagonal hydrate system MoO{sub 3}.nH{sub 2}O (napprox0.56). The unit cell lattice parameters are a=10.651 A, c=3.725 A and V=365.997 A{sup 3}. Scanning electron microscope (SEM) images of the as-deposited samples showed well-shaped hexagonal rods nuclei that grew and where the amount increased with increase in reaction time. X-ray photon electron spectroscopy (XPS) spectra showed a Gaussian shape of the doublet of Mo 3d core level, indicating the presence of Mo{sup 6+} oxidation state in the deposited films. The deposited films exhibited an electrochromic behavior by lithium intercalation and deintercalation, which resulted in coloration and bleaching of the film. Upon dehydration at about 450 deg. C, the hexagonal MoO{sub 3}.nH{sub 2}O was transformed into the thermodynamically stable orthorhombic phase. - Abstract: SEM photograph of typical h-MoO{sub 3}.nH{sub 2}O thin film nuclei obtained after 36 h at 40 deg. C by the LPD method. Display Omitted

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

    PubMed

    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. PMID:24782669

  17. Uranium trioxide behavior during electron energy loss spectroscopy analysis

    NASA Astrophysics Data System (ADS)

    Degueldre, Claude; Alekseev, Evgeny V.

    2015-03-01

    A sample of uranium trioxide (UO3) was produced by focused ion beam (~10 μm×~10 μm×<0.5 μm) for transmission electron and electron energy loss (EEL) spectroscopy examinations in a transmission electron microscope (TEM). The EEL spectra were recorded as a function of the thickness for the P and O edges in the low energy range 0-350 eV and were compared to spectra of UO3 small grains attached to a TEM grid. The EEL spectrum was studied through a range of thicknesses going from ~60 to ~260 nm. The EEL spectra recorded for UO3 are compared with those recorded for UO2. The reduction of UO3 into U4O9 and/or UO2 is readily observed apparently during the TEM investigations and as confirmed by electron diffraction (eD). This redox effect is similar to that known for other redox sensitive oxides. Recommendations are suggested to avoid sample decomposition.

  18. Photocatalysis and Photoelectrochemical Properties of Tungsten Trioxide Nanostructured Films

    PubMed Central

    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. PMID:24782669

  19. Photoresist removal using gaseous sulfur trioxide cleaning technology

    NASA Astrophysics Data System (ADS)

    Del Puppo, Helene; Bocian, Paul B.; Waleh, Ahmad

    1999-06-01

    A novel cleaning method for removing photoresists and organic polymers from semiconductor wafers is described. This non-plasma method uses anhydrous sulfur trioxide gas in a two-step process, during which, the substrate is first exposed to SO3 vapor at relatively low temperatures and then is rinsed with de-ionized water. The process is radically different from conventional plasma-ashing methods in that the photoresist is not etched or removed during the exposure to SO3. Rather, the removal of the modified photoresist takes place during the subsequent DI-water rinse step. The SO3 process completely removes photoresist and polymer residues in many post-etch applications. Additional advantages of the process are absence of halogen gases and elimination of the need for other solvents and wet chemicals. The process also enjoys a very low cost of ownership and has minimal environmental impact. The SEM and SIMS surface analysis results are presented to show the effectiveness of gaseous SO3 process after polysilicon, metal an oxide etch applications. The effects of both chlorine- and fluorine-based plasma chemistries on resist removal are described.

  20. Emissions of sulfur trioxide from coal-fired power plants.

    PubMed

    Srivastava, R K; Miller, C A; Erickson, C; Jambhekar, R

    2004-06-01

    Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough to not cause opacity violations and acid deposition. Generally, a small fraction of sulfur (S) in coal is converted to SO3 in coal-fired combustion devices such as electric utility boilers. The emissions of SO3 from such a boiler depend on coal S content, combustion conditions, flue gas characteristics, and air pollution devices being used. It is well known that the catalyst used in the selective catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small fraction of sulfur dioxide in the flue gas to SO3. The extent of this oxidation depends on the catalyst formulation and SCR operating conditions. Gas-phase SO3 and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and wet scrubber), result in fine acidic mist, which can cause increased plume opacity and undesirable emissions. Recently, such effects have been observed at plants firing high-S coal and equipped with SCR systems and wet scrubbers. This paper investigates the factors that affect acidic mist production in coal-fired electric utility boilers and discusses approaches for mitigating emission of this mist. PMID:15242154

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

    PubMed

    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. PMID:23842700

  2. Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation.

    PubMed

    Wang, Qian Qian; Zhou, Xin Yi; Zhang, Yan Fang; Bu, Na; Zhou, Jin; Cao, Feng Lin; Naranmandura, Hua

    2015-09-22

    Arsenic trioxide (As2O3) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As2O3, which results in initiation of PML-RARα degradation. However, after injection, As2O3 is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As2O3 (as iAs(III)) and its intermediate metabolites (i.e., MMA(III)/DMA(III)) in NB4 cells. Inorganic iAs(III) predominantly showed induction of cell differentiation, while MMA(III) and DMA(III) specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs(III), MMA(III) showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARα fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation. PMID:26213848

  3. Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation

    PubMed Central

    Zhang, Yan Fang; Bu, Na; Zhou, Jin; Cao, Feng Lin; Naranmandura, Hua

    2015-01-01

    Arsenic trioxide (As2O3) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As2O3, which results in initiation of PML-RARa degradation. However, after injection, As2O3 is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As2O3 (as iAsIII) and its intermediate metabolites (i.e., MMAIII/DMAIII) in NB4 cells. Inorganic iAsIII predominantly showed induction of cell differentiation, while MMAIII and DMAIII specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAsIII, MMAIII showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARa fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation. PMID:26213848

  4. Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.

    PubMed

    Hopkirk, R G

    1987-10-01

    An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock. PMID:16031332

  5. Arsenic Exposure and Toxicology: A Historical Perspective

    PubMed Central

    Hughes, Michael F.; Beck, Barbara D.; Chen, Yu; Lewis, Ari S.; Thomas, David J.

    2011-01-01

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve. PMID:21750349

  6. Avulsed Immature Permanent Central Incisors Obturated With Mineral Trioxide Aggregate: A Case Report

    PubMed Central

    Al-Kahtani, Ahmed

    2013-01-01

    The endodontic management of immature permanent incisors in young children can be challenging. This case reported an avulsed immature maxillary central incisors that underwent complete endodontic obturation using mineral trioxide aggregate. A 10-year-old male who suffered a fall injury avulsed both his central incisors. The revascularization process was not possible due to patient compliance and geographic reasons. Mineral trioxide aggregate was utilized as a novel endodontic treatment. After one year post-injury, the teeth remained symptom-free, the clinical and radiographic follow-up showed evidence of healthy periodontium. How to cite this article: Al-Kahtani A. Avulsed Immature Permanent Central Incisors Obturated With Mineral Trioxide Aggregate: A Case Report. J Int Oral Health 2013; 5(3):88-96. PMID:24155609

  7. The embryotoxic response to maternal chromium trioxide exposure in different strains of hamsters

    SciTech Connect

    Gale, T.F.

    1982-10-01

    This paper compares the chromium trioxide-induced embryotoxic effects among one noninbred (LVG) and five inbred (CB, LHC, LSH, MHA, PD4) strains of hamsters. A single dose of chromium trioxide (8 mg/kg, iv) was injected into pregnant hamsters on the morning of gestation Day 8. Treated and control animals were killed on gestation Day 15 and studied for the types and incidence of external and internal abnormalities, as well as the frequency of resorption sites per uterus. The embryotoxic effects described in this study include significant rates of resorptions, external abnormalities, cleft palate, and hydrocephalus. The results indicate that the MHA, LSH, and LVG strains are susceptible, while the CB, LHC, and PD4 strains are resistant to chromium trioxide-induced embryotoxicity. This study was compared with prior work in which the same hamster strains were treated with either cadmium, lead, or mercury.

  8. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  9. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  10. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  11. 40 CFR 61.180 - Applicability and designation of sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade...

  12. Arsenic content of homeopathic medicines

    SciTech Connect

    Kerr, H.D.; Saryan, L.A.

    1986-01-01

    In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations. Most sales personnel interviewed could not identify arsenic as being an ingredient in these preparations and were therefore incapable of warning the general public of possible dangers from ingestion. No such warnings appeared on the labels.

  13. Dye leakage and modification of fast-setting mineral trioxide aggregate.

    PubMed

    Challenger, Hereward; Lane, Jason; Becker, Ryan; Nassiripour, Sepehr; Torabinejad, Mahmoud

    2015-02-01

    The objective of this investigation was to determine and decrease dye leakage of fast-setting mineral trioxide aggregate (FSMTA). Specimens using differing setting times or concentrations of calcium sulfate modified FSMTA were assessed for dye penetration. Based on the results, no statistical difference was found in the dye leakage of FSMTA compared with regular mineral trioxide aggregate (MTA). The addition of 10 percent calcium sulfate resulted in a statistical reduction in dye leakage compared to both unmodified FSMTA and regular MTA. PMID:25868222

  14. Oxidations of cyclic {beta}-diketones catalyzed by methylrhenium trioxide

    SciTech Connect

    Abu-Omar, M.M.; Espenson, J.H. |

    1996-08-06

    Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) catalyzes the oxidation of {beta}-diketones by hydrogen peroxide. The kinetics of the initial oxidation step have been investigated in CH{sub 3}CN/H{sub 2}O (1:1 v/v) at 25{degree}C for a group of cyclic {beta}-diketones. The initial oxidation step features the enol form, the majority species, as the reactant. Its rate responds to substituents in the `normal` manner: electron-donating groups accelerate the reaction. We suggest that the double bond of the enol attacks a peroxo oxygen of a peroxorhenium complex A = CH{sub 3}Re(O){sub 2}(O{sub 2}) or B = CH{sub 3}Re(O)(O{sub 2}){sub 2}(H{sub 2}O). This reaction affords a 2-hydroxy-1,3-dicarbonyl intermediate, which in some instances was detected by {sup 1}H NMR. This hydroxy intermediate is susceptible to cleavage via a Baeyer-Villiger oxidation to yield carboxylic acids as final products. In contrast to the first reaction, this step may feature the peroxorhenium complexes A and B as nucleophiles rather than their customary electrophilic behavior; perhaps the trend is reversed by substrate binding to rhenium. Time profiles for the different stages of the reaction were also determined. The mechanistic aspects of these multistep catalytic oxidations are discussed in terms of the electronic nature of the activated rhenium-bound peroxo ligands. 38 refs., 3 figs., 3 tabs.

  15. Homicidal arsenic poisoning.

    PubMed

    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. PMID:25344454

  16. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  17. Classification of current anticancer immunotherapies

    PubMed Central

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  18. INFLUENCE OF DIETARY ARSENIC ON URINARY ARSENIC METABOLITE EXCRETION

    EPA Science Inventory

    Influence of Dietary Arsenic on Urinary Arsenic Metabolite Excretion

    Cara L. Carty, M.S., Edward E. Hudgens, B.Sc., Rebecca L. Calderon, Ph.D., M.S.P.H., Richard Kwok, M.S.P.H., Epidemiology and Biomarkers Branch/HSD, NHEERL/US EPA; David J. Thomas, Ph.D., Pharmacokinetics...

  19. A Phytoremediation Strategy for Arsenic

    SciTech Connect

    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. KINETIC AND DYNAMIC ASPECTS OF ARSENIC TOXICITY

    EPA Science Inventory

    This project integrates research on aspects of the kinetic and dynamic behavior of arsenic. A PBPK model for arsenic will be developed using metabolism and disposition data from studies in mice. Retention of arsenic in the tissues following exposure to arsenic will be investigate...

  1. OPTIMIZING ARSENIC REMOVAL DURING IRON REMOVAL PROCESSES

    EPA Science Inventory

    The recently promulgated Arsenic rule will require that many new drinking water systems treat their water to remove arsenic. Many groundwaters that have arsenic in their source water also have iron in their water. As a result, arsenic treatment at these sites will most likely b...

  2. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  3. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    EPA Science Inventory

    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...

  4. MECHANISMS OF ARSENICAL INDUCED MALFORMATIONS

    EPA Science Inventory

    Our research uses the whole embryo culture system to expose mouse embryos to arsenic at the neurulation stage of development (This stage of development is most susceptible to arsenical-induced defects). This includes studies to assess the distribution of cells in the cell cycle a...

  5. Arsenic Removal from Drinking Water

    EPA Science Inventory

    Web cast presentation covered six topics: 1), Arsenic Chemistry, 2), Technology Selection/Arsenic Demonstration Program, 3), Case Study 1, 4), Case Study 2,5), Case Study 3, and 6), Media Regeneration Project. The presentation consists of material presented at other training sess...

  6. ARSENIC TECHNICAL WORKSHOP PROCEEDINGS DOCUMENT

    EPA Science Inventory

    Arsenic is a semi-metallic element or metalloid which has several different allotropic forms. Arsenic compounds, mainly as As2O3, can be recovered as a by-product from processing complex ores mined for other minerals such as copper, lead, zinc, gold and silver. Consequently, ...

  7. Anticancer agents from marine sponges.

    PubMed

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  8. 78 FR 67141 - Antimony Trioxide (ATO) TSCA Chemical Risk Assessment; Notice of Public Meetings and Opportunity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... AGENCY Antimony Trioxide (ATO) TSCA Chemical Risk Assessment; Notice of Public Meetings and Opportunity... Substances Control Act (TSCA) chemical risk assessment, ``TSCA Workplan Chemical Risk Assessment for ATO... CONTACT: For technical information contact: Stan Barone, Jr., Risk Assessment Division (7403M), Office...

  9. Chemiluminescence in the oxidation of uranium (IV) by xenon trioxide and its analytical possibilities

    SciTech Connect

    Khamidullina, L.A.; Lotnik, S.V.; Gusev, Yu.K.; Kazakov, V.P.

    1988-09-01

    This work is devoted to an investigation of the previously detected chemiluminescence in the oxidation of uranium (IV) by xenone trioxide and to evaluating the possibility of using it in determining nanogram quantities of U/sup (IV)/ in solution, including solutions containing a large excess of U/sup (VI)/.

  10. Contribution to the photometric determination of small amounts of boron trioxide in glasses

    NASA Technical Reports Server (NTRS)

    Markova, D.

    1985-01-01

    The photometric determination for boron trioxide is described in amounts of 0-75 micrograms B2O3 with an azomethin H reagent. The yellow colored complex which occurs in a medium held at a pH of 4.5 was measured in light of a wavelength of 415 nm.

  11. PREVENTION REFERENCE MANUAL: CHEMICAL SPECIFIC. VOL. 15: CONTROL OF ACCIDENTAL RELEASES OF SULFUR TRIOXIDE

    EPA Science Inventory

    The report, discussing sulfur trioxide (SO3), is one of a series addressing the prevention of accidental releases of toxic chemicals. SO3, a clear oily liquid or solid at typical ambient conditions, has an Immediately Dangerous to Life and Health (IDLH) concentration of 20 ppm, w...

  12. A note on the biological activity of the noble gas compound xenon trioxide.

    NASA Technical Reports Server (NTRS)

    Siegel, S. M.; Smith, C. W.

    1972-01-01

    Comparison of xenon trioxide for toxicity in the few common oxidants using three bioassays. On a molar basis XeO3 and HOCl were similar, but XeO3 was less active than expected when comparisons were based on normality.

  13. Arsenic concentrations in Chinese coals.

    PubMed

    Wang, Mingshi; Zheng, Baoshan; Wang, Binbin; Li, Shehong; Wu, Daishe; Hu, Jun

    2006-03-15

    The arsenic concentrations in 297 coal samples were collected from the main coal-mines of 26 provinces in China were determined by molybdenum blue coloration method. These samples were collected from coals that vary widely in coal rank and coal-forming periods from the five main coal-bearing regions in China. Arsenic content in Chinese coals range between 0.24 to 71 mg/kg. The mean of the concentration of Arsenic is 6.4+/-0.5 mg/kg and the geometric mean is 4.0+/-8.5 mg/kg. The level of arsenic in China is higher in northeastern and southern provinces, but lower in northwestern provinces. The relationship between arsenic content and coal-forming period, coal rank is studied. It was observed that the arsenic contents decreases with coal rank in the order: Tertiary>Early Jurassic>Late Triassic>Late Jurassic>Middle Jurassic>Late Permian>Early Carboniferous>Middle Carboniferous>Late Carboniferous>Early Permian; It was also noted that the arsenic contents decrease in the order: Subbituminous>Anthracite>Bituminous. However, compared with the geological characteristics of coal forming region, coal rank and coal-forming period have little effect on the concentration of arsenic in Chinese coal. The average arsenic concentration of Chinese coal is lower than that of the whole world. The health problems in China derived from in coal (arsenism) are due largely to poor local life-style practices in cooking and home heating with coal rather than to high arsenic contents in the coal. PMID:16256172

  14. *Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate ciona intestinalis

    EPA Science Inventory

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt) , yielding mono-, di-, and trimethylated arsenicals. A comparative genomic approach focused on Ciona intestinaJis, an invertebrate chordate, was u...

  15. THE ROLE OF PROTEIN BINDING OF TRIVALENT ARSENICALS IN ARSENIC CARCINOGENESIS AND TOXICITY

    EPA Science Inventory

    Three of the most plausible biological theories of arsenic carcinogenesis are protein binding, oxidative stress and altered DNA methylation. This review presents the role of trivalent arsenicals binding to proteins in arsenic carcinogenesis. Using vacuum filtration based receptor...

  16. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1995-01-01

    Methods and apparatus for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short.

  17. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1994-01-01

    Methods and apparatus for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short.

  18. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, D.R.

    1994-12-06

    Methods and apparatus are described for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72. The invention provides apparatus which can be located at a site where arsenic-72 is used, for purposes such as PET imaging, to produce arsenic-72 as needed, since the half-life of arsenic-72 is very short. 2 figures.

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

    PubMed Central

    Chen, Liguo; Chen, Ruixue

    2016-01-01

    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. PMID:27382405

  20. Mitophagy inhibits proliferation by decreasing cyclooxygenase-2 (COX-2) in arsenic trioxide-treated HepG2 cells.

    PubMed

    Niu, Zhidan; Zhang, Wenya; Gu, Xueyan; Zhang, Xiaoning; Qi, Yongmei; Zhang, Yingmei

    2016-07-01

    Mitochondrial damage can trigger mitophagy and eventually suppress proliferation. However, the effect of mitophagy on proliferation remains unclear. In this study, HepG2 cells were used to assess mitophagy and proliferation arrest in response to As2O3 exposure. The stimulatory effect of As2O3 on mitophagy was investigated by assessing morphology (mitophagosome and mitolysosome) and relevant proteins (PINK1, LC3 II/I, and COX IV). Additionally, the relationship of mitophagy and proliferation was explored through the use of mitophagy inhibitors (CsA, Mdivi-1). Interestingly, the inhibition of mitophagy rescued proliferation arrest by restoring COX-2 protein level and countered the elimination of mitochondria-located COX-2 and up-regulated the COX-2 mRNA level. Taken together, our findings indicated that mitophagy can be induced and can inhibit proliferation by reducing COX-2 in HepG2 cells during As2O3 treatment. PMID:27318970

  1. Anticancer Activity of Amauroderma rude

    PubMed Central

    Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B.

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities. PMID:23840494

  2. In situ chemical fixation of arsenic-contaminated soils: Anexperimental study

    SciTech Connect

    Yang, Li; Donahoe, Rona J.; Redwine, James C.

    2007-03-27

    This paper reports the results of an experimentalstudytesting a low-cost in situ chemical fixation method designed to reclaimarsenic-contaminated subsurface soils. Subsurface soils from severalindustrial sites in southeastern U.S. were contaminated with arsenicthrough heavy application of herbicide containing arsenic trioxide. Themean concentrations of environmentally available arsenic in soilscollected from the two study sites, FW and BH, are 325 mg/kg and 900mg/kg, respectively. The soils are sandy loams with varying mineralogicaland organic contents. The previous study [Yang L, Donahoe RJ. The form,distribution and mobility of arsenic in soils contaminated by arsenictrioxide, at sites in Southeast USA. Appl Geochem 2007;22:320 341]indicated that a large portion of the arsenic in both soils is associatedwith amorphous aluminum and iron oxyhydroxides and shows very slowrelease against leaching by synthetic precipitation. The soil's amorphousaluminum and iron oxyhydroxides content was found to have the mostsignificant effect on its ability to retain arsenic.Based on thisobservation, contaminated soils were reacted with different treatmentsolutions in an effort to promote the formation of insolublearsenic-bearing phases and thereby decrease the leachability of arsenic.Ferrous sulfate, potassium permanganate and calcium carbonate were usedas the reagents for the chemical fixation solutions evaluated in threesets of batch experiments: (1) FeSO4; (2) FeSO4 and KMnO4; (3) FeSO4,KMnO4 and CaCO3. The optimum treatment solutions for each soil wereidentified based on the mobility of arsenic during sequential leaching oftreated and untreated soils using the fluids described in EPA Method 1311[USEPA. Method 1311: toxicity characteristic leaching procedure. Testmethods for evaluating solid waste, physical/chemical methods. 3rd ed.Washington, DC: U.S. Environmental Protection Agency, Office of SolidWaste. U.S. Government Printing Office; 1992]toxic characteristicsleaching

  3. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated ars...

  4. Enhanced coagulation for arsenic removal

    SciTech Connect

    Cheng, R.C.; Liang, S.; Wang, H.C.; Beuhler, M.D. )

    1994-09-01

    The possible use of enhanced coagulation for arsenic removal was examined at the facilities of a California utility in 1992 and 1993. The tests were conducted at bench, pilot, and demonstration scales, with two source waters. Alum and ferric chloride, with cationic polymer, were investigated at various influence arsenic concentrations. The investigators concluded that for the source waters tested, enhanced coagulation could be effective for arsenic removal and that less ferric chloride than alum, on a weight basis, is needed to achieve the same removal.

  5. Arsenic behavior in newly drilled wells

    USGS Publications Warehouse

    Kim, M.-J.; Nriagu, J.; Haack, S.

    2003-01-01

    In the present paper, inorganic arsenic species and chemical parameters in groundwater were determined to investigate the factors related to the distribution of arsenic species and their dissolution from rock into groundwater. For the study, groundwater and core samples were taken at different depths of two newly drilled wells in Huron and Lapeer Counties, Michigan. Results show that total arsenic concentrations in the core samples varied, ranging from 0.8 to 70.7 mg/kg. Iron concentration in rock was about 1800 times higher than that of arsenic, and there was no correlation between arsenic and iron occurrences in the rock samples. Arsenic concentrations in groundwater ranged from <1 to 171 ??g/l. The arsenic concentration in groundwater depended on the amount of arsenic in aquifer rocks, and as well decreased with increasing depth. Over 90% of arsenic existed in the form of As(III), implying that the groundwater systems were in the reduced condition. The results such as high ferrous ion, low redox potential and low dissolved oxygen supported the observed arsenic species distribution. There was no noticeable difference in the total arsenic concentration and arsenic species ratio between unfiltered and filtered (0.45 ??m) waters, indicating that the particulate form of arsenic was negligible in the groundwater samples. There were correlations between water sampling depth and chemical parameters, and between arsenic concentration and chemical parameters, however, the trends were not always consistent in both wells. ?? 2003 Elsevier Science Ltd. All rights reserved.

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

    SciTech Connect

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    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

  7. Association of oxidative stress with arsenic methylation in chronic arsenic-exposed children and adults

    SciTech Connect

    Xu Yuanyuan; Wang Yi; Zheng Quanmei; Li Xin; Li Bing; Jin Yaping; Sun Xiance; Sun Guifan

    2008-10-01

    Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.

  8. Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats

    PubMed Central

    Wang, Xiaona; Zhao, Haiyuan; Shao, Yilan; Wang, Pei; Wei, Yanru; Zhang, Weiqian; Jiang, Jing; Chen, Yan

    2014-01-01

    Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy. PMID:24611105

  9. [Arsenic as an environmental problem].

    PubMed

    Jensen, K

    2000-12-01

    Chronic exposure to arsenic through drinking water is known in different continents. Arsenic compounds from disintegrating rock may be solubilized after reduction by organic material, and harmful concentrations of arsenic may be found in surface water as well as in water from drilled wells. Because of well drilling since the sixties in the Ganges delta numerous millions of people have been exposed to toxic amounts, and hundreds of thousands demonstrate signs of chronic poisoning. A changed water technology and chemical precipitation of arsenic in the drinking water can reduce the size of the problem, but the late sequelae i.e. malignant disease are incalculable. Indications for antidotal treatment of exposed individuals have not yet been outlined. PMID:11188053

  10. THE PATHWAY OF ARSENIC METABLISM

    EPA Science Inventory

    The Pathway of Arsenic Methylation

    David J. Thomas, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC

    Understanding ...

  11. ARSENIC TREATMENT BY ADSORPTIVE TECHNOLOGY

    EPA Science Inventory

    Presentation will discuss the removal of arsenic from drinking water using the adsorptive media treatment process. Fundamental information is provided on the design and operation of adsorptive media technology including the selection of the adsorptive media. The information cites...

  12. Anticancer Molecular Mechanisms of Resveratrol

    PubMed Central

    Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

    2016-01-01

    Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment. PMID:27148534

  13. Copper complexes as anticancer agents.

    PubMed

    Marzano, Cristina; Pellei, Maura; Tisato, Francesco; Santini, Carlo

    2009-02-01

    Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field. PMID:19199864

  14. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  15. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  16. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  17. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  18. 40 CFR 61.186 - Reporting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... alternative arsenic trioxide production processes. Conclusions and recommendations of the studies shall...

  19. Life and death with arsenic

    PubMed Central

    Rosen, Barry P.; Ajees, A. Abdul; McDermott, Timothy R.

    2013-01-01

    Arsenic and phosphorus are group 15 elements with similar chemical properties. Is it possible that arsenate could replace phosphate in some of the chemicals that are required for life? Phosphate esters are ubiquitous in biomolecules and are essential for life, from the sugar phosphates of intermediary metabolism to ATP to phospholipids to the phosphate backbone of DNA and RNA. Some enzymes that form phosphate esters catalyze the formation of arsenate esters. Arsenate esters hydrolyze very rapidly in aqueous solution, which makes it improbable that phosphorous could be completely replaced with arsenic to support life. Studies of bacterial growth at high arsenic:phosphorus ratios demonstrate that relatively high arsenic concentrations can be tolerated, and that arsenic can become involved in vital functions in the cell, though likely much less efficiently than phosphorus. Recently Wolfe-Simon et al. [1] reported the isolation of a microorganism that they maintain uses arsenic in place of phosphorus for growth. Here, we examine and evaluate their data and conclusions. PMID:21387349

  20. Arsenic removal by ferric chloride

    SciTech Connect

    Hering, J.G.; Chen, P.Y.; Wilkie, J.A.; Elimelech, M.; Liang, S.

    1996-04-01

    Bench-scale studies were conducted in model freshwater systems to investigate how various parameters affected arsenic removal during coagulation with ferric chloride and arsenic adsorption onto preformed hydrous ferric oxide. Parameters included arsenic oxidation state and initial concentration, coagulant dosage or adsorbent concentration, pH, and the presence of co-occurring inorganic solutes. Comparison of coagulation and adsorption experiments and of experimental results with predictions based on surface complexation modeling demonstrated that adsorption is an important (though not the sole) mechanism governing arsenic removal during coagulation. Under comparable conditions, better removal was observed with arsenic(V) [As(V)] than with arsenic(III) [As(III)] in both coagulation and adsorption experiments. Below neutral pH values, As(III) removal-adsorption was significantly decreased in the presence of sulfate, whereas only a slight decrease in As(V) removal-adsorption was observed. At high pH, removal-adsorption of As(V) was increased in the presence of calcium. Removal of As(V) during coagulation with ferric chloride is both more efficient and less sensitive than that of As(III) to variations in source water composition.

  1. Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

    PubMed

    Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin

    2015-01-01

    Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections. PMID:25751009

  2. Arsenic Toxicity in Male Reproduction and Development

    PubMed Central

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-01-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children’s health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity. PMID:26973968

  3. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity. PMID:26973968

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

    ERIC Educational Resources Information Center

    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…

  5. Arsenic Toxicity to Juvenile Fish: Effects of Exposure Route, Arsenic Speciation, and Fish Species

    EPA Science Inventory

    Arsenic toxicity to juvenile rainbow trout and fathead minnows was evaluated in 28-day tests using both dietborne and waterborne exposures, both inorganic and organic arsenic species, and both a live diet and an arsenic-spiked pellet diet. Effects of inorganic arsenic on rainbow...

  6. Treatment of Internal Resorption with Mineral Trioxide Aggregates: A Case Report

    PubMed Central

    Yadav, Pankaj; Rao, Yogesh; Jain, Anurag; Relhan, Nikhil; Gupta, Sandeep

    2013-01-01

    Tooth resorption is a common sequel which follows injuries or irritation to the periodontal ligament and/or tooth pulp. The course of tooth resorption involves an elaborate interaction among inflammatory cells, resorbing cells, and hard tissue structures. The key cells which are involved in resorption are multi–nucleated giant cells. Internal root resorptions are usually non–symptomatic and they are discovered occasionally through periapical radiographs, which reveal very defined and regular outlines. Many techniques and materials have been used to fill internal resorptive defects. Among them, Mineral Trioxide Aggregates (MTAs) have satisfactory properties, which include: biocompatibility, a favourable sealing ability, mechanical strength and a capacity to promote a periradicular tissue healing. Thus, a Mineral Trioxide Aggregate (MTA) repair of a maxillary left central incisor tooth with an inflammatory resorptive defect, in the middle third of the root canal, has been reported here. PMID:24298543

  7. Summary of the Preliminary Analysis of Savannah River Depleted Uranium Trioxide

    SciTech Connect

    NSTec Environmental Management

    2010-10-13

    This report summarizes a preliminary special analysis of the Savannah River Depleted Uranium Trioxide waste stream (SVRSURANIUM03, Revision 2). The analysis is considered preliminary because a final waste profile has not been submitted for review. The special analysis is performed to determine the acceptability of the waste stream for shallow land burial at the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada National Security Site (NNSS). The Savannah River Depleted Uranium Trioxide waste stream requires a special analysis because the waste stream’s sum of fractions exceeds one. The 99Tc activity concentration is 98 percent of the NNSS Waste Acceptance Criteria and the largest single contributor to the sum of fractions.

  8. Mineral trioxide aggregate: a review of the constituents and biological properties of the material.

    PubMed

    Camilleri, J; Pitt Ford, T R

    2006-10-01

    This paper reviews the literature on the constituents and biocompatibility of mineral trioxide aggregate (MTA). A Medline search was conducted. The first publication on the material was in November 1993. The Medline search identified 206 papers published from November 1993 to August 2005. Specific searches on constituents and biocompatibility of mineral trioxide aggregate, however, yielded few publications. Initially all abstracts were read to identify which fitted one of the two categories required for this review, constituents or biocompatibility. Based on this assessment and a review of the papers, 13 were included in the constituent category and 53 in the biocompatibility category. Relatively few articles addressed the constituents of MTA, whilst cytological evaluation was the most widely used biocompatibility test. PMID:16948659

  9. Mechanism for forming hydrogen chloride and sodium sulfate from sulfur trioxide, water, and sodium chloride

    NASA Technical Reports Server (NTRS)

    Anderson, A. B.

    1984-01-01

    A molecular orbital study of sodium sulfate and hydrogen chloride formation from sulfur trioxide, water, and sodium chloride shows no activation barrier, in agreement with recent experimental work of Kohl, Fielder, and Stearns. Two overall steps are found for the process. First, gas-phase water reacts with sulfur trioxide along a pathway involving a linear O-H-O transition state yielding closely associated hydroxyl and bisulfite which rearrange to become a hydrogen sulfate molecule. Then the hydrogen sulfate molecule transfers a hydrogen atom to a surface chloride in solid sodium chloride while an electron and a sodium cation simultaneously transfer to yield sodium bisulfate and gas-phase hydrogen chloride. This process repeats. Both of these steps represent well-known reactions for which mechanisms have not been previously determined.

  10. Treatment of internal resorption with mineral trioxide aggregates: a case report.

    PubMed

    Yadav, Pankaj; Rao, Yogesh; Jain, Anurag; Relhan, Nikhil; Gupta, Sandeep

    2013-10-01

    Tooth resorption is a common sequel which follows injuries or irritation to the periodontal ligament and/or tooth pulp. The course of tooth resorption involves an elaborate interaction among inflammatory cells, resorbing cells, and hard tissue structures. The key cells which are involved in resorption are multi-nucleated giant cells. Internal root resorptions are usually non-symptomatic and they are discovered occasionally through periapical radiographs, which reveal very defined and regular outlines. Many techniques and materials have been used to fill internal resorptive defects. Among them, Mineral Trioxide Aggregates (MTAs) have satisfactory properties, which include: biocompatibility, a favourable sealing ability, mechanical strength and a capacity to promote a periradicular tissue healing. Thus, a Mineral Trioxide Aggregate (MTA) repair of a maxillary left central incisor tooth with an inflammatory resorptive defect, in the middle third of the root canal, has been reported here. PMID:24298543

  11. Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report

    PubMed Central

    WU, SUIJING; XU, LING; HUANG, XIN; GENG, SUXIA; XU, YAN; CHEN, SHAOHUA; YANG, LIJIAN; WU, XIULI; WENG, JANYU; DU, XIN; LI, YANGQIU

    2016-01-01

    Currently, arsenic trioxide therapy is widely used for the treatment of acute promyelocytic leukemia (APL), relapsed and refractory adult T-cell leukemia/lymphoma and myelodysplastic syndrome. Regarding the broad antitumor activity of arsenic, certain studies have been undertaken to test its efficacy in treating acute T-cell lymphoblastic leukemia (T-ALL) cell lines and patients; however, to the best of our knowledge, no reports document that arsenic is able to induce the remission of T-ALL patients. The present study reports the case of young male patient diagnosed with T-ALL, with no significant response to common chemotherapy regimens, who finally achieved complete remission without minimal residual disease (as detected by flow cytometry) due to arsenic treatment. This result is encouraging, and the present study has shown that malignant TCRαβ+ cell clones can be detected at the molecular level using reverse transcription-polymerase chain reaction (PCR) combined with the GeneScan technique. The result is mainly based on the T-cell receptor (TCR) Vβ1 clone (a 190-base pair PCR product that with the same complementarity determining region 3 length can be detected for all samples collected during various statuses) and on undetectable TCR Vγ subfamily members, at the time of disease diagnosis. It is important to analyze the dynamically changing TCR pool in leukemia patients during therapy. Although the molecular mechanism through which arsenic contributes to malignant clone elimination remains unclear in the case presented, the use of arsenic is expected to be effective for clinically treating refractory and relapsed T-ALL patients. PMID:27313752

  12. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    SciTech Connect

    Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

    2011-06-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  13. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells.

    PubMed

    Sides, Mark D; Block, Gregory J; Shan, Bin; Esteves, Kyle C; Lin, Zhen; Flemington, Erik K; Lasky, Joseph A

    2011-07-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies. PMID:21605886

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Surgical management of iatrogenic perforation in maxillary central incisor using mineral trioxide aggregate

    PubMed Central

    Nagpal, Rajni; Manuja, Naveen; Pandit, I K; Rallan, Mandeep

    2013-01-01

    Root perforations are undesired complications of endodontic treatment. The repair of root perforation can be accomplished using different materials and techniques. Mineral trioxide aggregate (MTA) is widely used to seal perforations because of its biocompatibility and sealability. This article describes a case report where an iatrogenic root perforation was repaired successfully with MTA in maxillary right central incisor of a 13-year-old boy. PMID:23845686

  16. Comparison of radiation shielding ratios of nano-sized bismuth trioxide and molybdenum

    NASA Astrophysics Data System (ADS)

    Cho, J. H.; Kim, M. S.; Rhim, J. D.

    2015-07-01

    In this study, radiation shielding fibers using non-hazardous nano-sized bismuth trioxide and molybdenum instead of lead were developed and evaluated. Among the elements with high densities and atomic numbers, non-hazardous elements such as bismuth trioxide and molybdenum were chosen as a shielding element. Then, bismuth trioxide (Bi2O3) with average particle size 1-500 µm was ball milled for 10 min to produce a powdered form of nanoparticles with average particle size of 10-100 nm. Bismuth trioxide nanoparticles were dispersed to make a colloidal suspension, followed by spreading and hardening onto one or two sides of fabric, to create the radiation shielding fabric. The thicknesses of the shielding sheets using nano-sized bismuth and molybdenum were 0.4 and 0.7 mm. According to the lead equivalent test of X-ray shielding products suggested by KS, the equivalent dose was measured, followed by calculation of the shielding rate. The shielding rate of bismuth with 0.4 mm thickness and at 50 kVp was 90.5%, which is comparable to lead of 0.082 mm thickness. The shielding rate of molybdenum was 51.89%%, which is comparable to lead of 0.034 mm. At a thickness of 0.7 mm, the shielding rate of bismuth was 98.73%, equivalent to 0.101 mm Pb, whereas the shielding rate of molybdenum was 74.68%, equivalent to 0.045 mm Pb. In conclusion, the radiation shielding fibers using nano-sized bismuth developed in this study are capable of reducing radiation exposure by X-ray and its low-dose scatter ray.

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

    PubMed

    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. PMID:25666567

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

    PubMed

    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. PMID:23466730

  19. Arsenic Speciation in Groundwater: Role of Thioanions

    EPA Science Inventory

    The behavior of arsenic in groundwater environments is fundamentally linked to its speciation. Understanding arsenic speciation is important because chemical speciation impacts reactivity, bioavailability, toxicity, and transport and fate processes. In aerobic environments arsen...

  20. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, Dennis R.

    1993-01-01

    Methods for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72.

  1. Production of selenium-72 and arsenic-72

    DOEpatents

    Phillips, D.R.

    1993-04-20

    Methods are described for producing selenium-72, separating it from its daughter isotope arsenic-72, and generating multiple portions of a solution containing arsenic-72 from a reusable parent substance comprised of selenium-72.

  2. Arsenic - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arsenic URL of this page: https://www.nlm.nih.gov/medlineplus/languages/arsenic.html Other topics A-Z A B ...

  3. Plutonium and transplutonium element trioxides: molecular structures, chemical bonding, and isomers.

    PubMed

    Zaitsevskii, Andréi

    2015-10-14

    Ground-state equilibrium geometries, energetics, and vibrational frequencies of AnO3 molecules, An = Pu through Cf, and their isomers are calculated using an accurate small-core pseudopotential model and the two-component relativistic density functional theory. The qualitative features of chemical bonding in these molecules are discussed in terms of oxidation states and bond orders. The actinide oxidation state (VI) is reached only in the plutonium trioxide molecule, whereas heavier actinide atoms in T-shaped trioxide molecules should be considered as pentavalent. At least at low temperatures, PuO3 and, to a lesser degree, AmO3 and BkO3 molecules should be stable both with respect to the isomerization into oxoperoxides or oxosuperoxides and the decay into dioxides and molecular oxygen. These trioxides can form dimers with significant (above 250 kJ mol(-1)) dissociation energies; the oxidation states of actinide atoms in the lowest-energy configurations of these dimers coincide with those in the corresponding monomers. The ability to reach high oxidation states in oxygen compounds gradually decreases from Pu onwards, with the only exception being the unexpectedly stable Bk(v)O3. PMID:26343514

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

    PubMed

    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. PMID:25148047

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Electrosprayed Molybdenum Trioxide Aqueous Solution and Its Application in Organic Photovoltaic Cells

    PubMed Central

    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. PMID:25148047

  7. Heterocyclic chalcone analogues as potential anticancer agents.

    PubMed

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  8. Mobility of arsenic in soil from the Rocky Mountain Arsenal area

    NASA Astrophysics Data System (ADS)

    Corwin, D. L.; David, A.; Goldberg, S.

    1999-07-01

    From 1942 to the early 1980s, Rocky Mountain Arsenal (RMA), a superfund site northeast of Denver in central Colorado, served as a facility for the development, manufacture, and disposal of toxic organic and inorganic chemicals including US Army surety agents (including nerve gas and blistering agents), munitions, propellants, and pesticides. Arsenic (As) in the form of Lewisite (blistering agent), arsenic trioxide (herbicide), trisodium arsenate, and arsenic trichloride (process intermediate) was present in extremely large quantities at RMA's South Plants Processing Area. Even though current cleanup efforts are likely to remove the vast majority of As presently polluting the soil and groundwater, there is still a future potential threat for the movement of residual levels of As into groundwater supplies. The distribution and movement of As were monitored over a 2.5-year period to evaluate the threat to groundwater by low levels of As. Because of access restrictions to RMA, an off-site meso-scale (0.6 m diameter by 1.83 m in height) weighing lysimeter study was conducted using excavated soil (i.e., Ascalon sandy clay loam) associated with As contamination at RMA's South Plants Processing Area. The long-term study revealed the persistence of As under aerobic soil conditions, and a limited, but perceptible, mobility of As (0.87% of the total applied As drained beyond 1.5 m) resulting from interacting physical, chemical, and biological factors. Results suggest that even though the movement of As is significantly retarded due to adsorptive processes, preferential flow and chemical factors (i.e., pH and redox potential) can mobilize As at point locations above permissible levels, if precautionary measures are not taken.

  9. GROUND WATER TREATMENT PROCESSES FOR ARSENIC REMOVAL

    EPA Science Inventory

    In 1975 EPA established a maximum contaminant level (MCL) for arsenic at 0.05 mg/L. In 1996, Congress amended the SDWA and these amendments required that EPA develop an arsenic research strategy and publish a proposal to revise the arsenic MCL by January 2000. The Agency proposed...

  10. Linking Arsenic Metabolism and Toxic Effects

    EPA Science Inventory

    Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

  11. Arsenic Metabolism and Distribution in Developing Organisms

    EPA Science Inventory

    A growing body of evidence suggests that exposure to inorganic arsenic during early life has long term adverse effects. The extent of exposure to inorganic arsenic and its methylated metabolites in utero is determined not only by the rates of formation and transfer of arsenicals...

  12. Arsenic Exposure and Toxicology: A Historical Perspective

    EPA Science Inventory

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, in various forms, has also been used as a pesticide and a ch...

  13. SPECIATION OF ARSENIC IN EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

    The speciaton of arsenic in water, food and urine are analytical capabilities which are an essential part in arsenic risk assessment. The cancer risk associated with arsenic has been the driving force in generating the analytical research in each of these matrices. This presentat...

  14. 21 CFR 556.60 - Arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Arsenic. 556.60 Section 556.60 Food and Drugs FOOD... New Animal Drugs § 556.60 Arsenic. (a) (b) Tolerances. The tolerances for total residue of combined arsenic (calculated as As) are: (1) Turkeys—(i) Muscle and eggs: 0.5 parts per million (ppm). (ii)...

  15. Arsenic - Multiple Languages: MedlinePlus

    MedlinePlus

    ... 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 ...

  16. TYPES OF ARSENIC AND TREATMENT OPTIONS

    EPA Science Inventory

    Presentation will discuss the state-of-the-art technology for removal of arsenic from drinking water. Presentation includes results of several EPA field studies on removal of arsenic from existing arsenic removal plants and key results from several EPA sponsored research studies...

  17. Transplacental arsenic carcinogenesis in mice

    SciTech Connect

    Waalkes, Michael P. Liu, Jie; Diwan, Bhalchandra A.

    2007-08-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

  18. BREAST CANCER, DERMATOFIBROMAS AND ARSENIC

    PubMed Central

    Dantzig, Paul I

    2009-01-01

    Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. Results: The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Conclusions: Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer. PMID:20049264

  19. Arsenic, Anaerobes, and Autotrophy.

    NASA Astrophysics Data System (ADS)

    Oremland, R. S.

    2008-12-01

    That microbes have resistance to the toxic arsenic oxyanions arsenite [As(III)] and arsenate [As(V)] has been recognized for some time. More recently it was shown that certain prokaryotes can demonstrate As- dependent growth by conserving the energy gained from the aerobic oxidation of As(III) to As(V), or from the reduction of As(V) to As(III) under anaerobic conditions. During the course of our field studies of two alkaline, hypersaline soda lakes (Mono Lake and Searles Lake, CA) we have discovered several new anaerobic chemo- and photo-autotrophic bacteria that can center their energy gain around the redox reactions between As(III) and As(V). Alkalilimnicola ehrlichii, isolated from the water column of Mono Lake is a nitrate-respiring, As(III)-oxidizing chemoautotroph of the gamma-proteobacteria that has a highly flexible metabolism. It can function either as a facultative anaerobe or as a chemo-autotroph, or as a heterotroph (Hoeft et al., 2007). In contrast, strain MLMS-1 of the delta-proteobacteria was also isolated from Mono Lake, but to date is the first example of an obligate As(V)-respirer that is also an obligate chemo-autotroph, gaining its energy via the oxidation of sulfide to sulfate (Hoeft et al., 2004). Strain SLAS-1, isolated from salt-saturated Searles Lake is a member of the Halananerobiales, and can either grow as a heterotroph (lactate e-donor) or chemo- autotroph (sulfide e-donor) while respiring As(V). The fact that it can achieve this feat at salt-saturation (~ 340 g/L) makes it a true extremophile (Oremland et. al., 2005). Finally, strain PHS-1 isolated from a hot spring on Paoha island in Mono Lake is the first example of a photosynthetic bacterium of the gamma- proteobacteria able to link its growth to As(III)-dependent anoxygenic photosynthesis (Kulp et al., 2008). These novel microbes give us new insights into the evolution of arsenic-based metabolism and their role in the biogeochemical cycling of this toxic element. Hoeft, S.E., et

  20. Electronic structure of trioxide, oxoperoxide, oxosuperoxide, and ozonide clusters of the 3d elements: density functional theory study.

    PubMed

    Uzunova, Ellie L

    2011-03-01

    The trioxide clusters with stoichiometry MO3, and the structural isomers with side-on and end-on bonded oxygen atoms, are studied by DFT with the B1LYP functional. For the first half of the 3d elements row (Sc to Cr), pyramidal or distorted pyramidal structures dominate among the trioxide and oxoperoxide ground states, while the remaining elements form planar trioxides, oxoperoxides, oxosuperoxides, and ozonides. Low-lying trioxide clusters are formed by Ti, V, Cr, and Mn, among which the distorted pyramidal VO3 in the (2)A'' state, the pyramidal CrO3 in the (1)A1 state, and the planar MnO3 in the (2)A1' state are global minima. With the exception of the middle-row elements Mn, Fe, and Co, the magnetic moment of the ground-state clusters is formed with a major contribution from unpaired electrons located at the oxygen atoms. The stability of trioxides and oxoperoxides toward release of molecular oxygen is significantly higher for Sc, Ti, and V than for the remaining elements of the row. A trend of increasing the capability to dissociate one oxygen molecule is observed from Cr to Cu, with the exception of OFe(O2) being more reactive than OCo(O2). A gradual increase of reactivity from Ti to Cu is observed for the complete fragmentation reaction M + O + O2. PMID:21299242

  1. Mineral resource of the month: arsenic

    USGS Publications Warehouse

    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.

  2. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    USGS Publications Warehouse

    Wang, M.; Song, D.; Zheng, B.; Finkelman, R.B.

    2008-01-01

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong. ?? 2008 New York Academy of Sciences.

  3. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    SciTech Connect

    Mingshi Wang; Dangyu Song; Baoshan Zheng; R.B. Finkelman

    2008-10-15

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong.

  4. Ganoderma: insights into anticancer effects.

    PubMed

    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists. PMID:26317382

  5. Novel antibodies as anticancer agents.

    PubMed

    Zafir-Lavie, I; Michaeli, Y; Reiter, Y

    2007-05-28

    In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents. PMID:17530025

  6. Arsenic Contamination in Food-chain: Transfer of Arsenic into Food Materials through Groundwater Irrigation

    PubMed Central

    Joardar, J.C.; Parvin, S.; Correll, Ray; Naidu, Ravi

    2006-01-01

    Arsenic contamination in groundwater in Bangladesh has become an additional concern vis-à-vis its use for irrigation purposes. Even if arsenic-safe drinking-water is assured, the question of irrigating soils with arsenic-laden groundwater will continue for years to come. Immediate attention should be given to assess the possibility of accumulating arsenic in soils through irrigation-water and its subsequent entry into the food-chain through various food crops and fodders. With this possibility in mind, arsenic content of 2,500 water, soil and vegetable samples from arsenic-affected and arsenic-unaffected areas were analyzed during 1999–2004. Other sources of foods and fodders were also analyzed. Irrigating a rice field with groundwater containing 0.55 mg/L of arsenic with a water requirement of 1,000 mm results in an estimated addition of 5.5 kg of arsenic per ha per annum. Concentration of arsenic as high as 80 mg per kg of soil was found in an area receiving arsenic-contaminated irrigation. A comparison of results from affected and unaffected areas revealed that some commonly-grown vegetables, which would usually be suitable as good sources of nourishment, accumulate substantially-elevated amounts of arsenic. For example, more than 150 mg/kg of arsenic has been found to be accumulated in arum (kochu) vegetable. Implications of arsenic ingested in vegetables and other food materials are discussed in the paper. PMID:17366772

  7. Arsenic occurrence in New Hampshire drinking water

    SciTech Connect

    Peters, S.C.; Blum, J.D.; Klaue, B.; Karagas, M.R.

    1999-05-01

    Arsenic concentrations were measured in 992 drinking water samples collected from New Hampshire households using online hydride generation ICP-MS. These randomly selected household water samples contain much less arsenic than those voluntarily submitted for analysis to the New Hampshire Department of Environmental Services (NHDES). Extrapolation of the voluntarily submitted sample set to all New Hampshire residents significantly overestimates arsenic exposure. In randomly selected households, concentrations ranged from <0.0003 to 180 {micro}g/L, with water from domestic wells containing significantly more arsenic than water from municipal sources. Water samples from drilled bedrock wells had the highest arsenic concentrations, while samples from surficial wells had the lowest arsenic concentrations. The authors suggest that much of the groundwater arsenic in New Hampshire is derived from weathering of bedrock materials and not from anthropogenic contamination. The spatial distribution of elevated arsenic concentrations correlates with Late-Devonian Concord-type granitic bedrock. Field observations in the region exhibiting the highest groundwater arsenic concentrations revealed abundant pegmatite dikes associated with nearby granites. Analysis of rock digests indicates arsenic concentrations up to 60 mg/kg in pegmatites, with much lower values in surrounding schists and granites. Weak acid leaches show that approximately half of the total arsenic in the pegmatites is labile and therefore can be mobilized during rock-water interaction.

  8. Removal processes for arsenic in constructed wetlands.

    PubMed

    Lizama A, Katherine; Fletcher, Tim D; Sun, Guangzhi

    2011-08-01

    Arsenic pollution in aquatic environments is a worldwide concern due to its toxicity and chronic effects on human health. This concern has generated increasing interest in the use of different treatment technologies to remove arsenic from contaminated water. Constructed wetlands are a cost-effective natural system successfully used for removing various pollutants, and they have shown capability for removing arsenic. This paper reviews current understanding of the removal processes for arsenic, discusses implications for treatment wetlands, and identifies critical knowledge gaps and areas worthy of future research. The reactivity of arsenic means that different arsenic species may be found in wetlands, influenced by vegetation, supporting medium and microorganisms. Despite the fact that sorption, precipitation and coprecipitation are the principal processes responsible for the removal of arsenic, bacteria can mediate these processes and can play a significant role under favourable environmental conditions. The most important factors affecting the speciation of arsenic are pH, alkalinity, temperature, dissolved oxygen, the presence of other chemical species--iron, sulphur, phosphate--,a source of carbon, and the wetland substrate. Studies of the microbial communities and the speciation of arsenic in the solid phase using advanced techniques could provide further insights on the removal of arsenic. Limited data and understanding of the interaction of the different processes involved in the removal of arsenic explain the rudimentary guidelines available for the design of wetlands systems. PMID:21549410

  9. Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water

    PubMed Central

    2013-01-01

    Background Limited data exist on the contribution of dietary sources of arsenic to an individual’s total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest. Methods Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 μg/L versus ≥1 μg/L. Results As expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (≥1 μg/L). Conclusions This study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential

  10. Arsenic contamination of Bangladesh paddy field soils: implications for rice contribution to arsenic consumption.

    PubMed

    Meharg, Andrew A; Rahman, Md Mazibur

    2003-01-15

    Arsenic contaminated groundwater is used extensively in Bangladesh to irrigate the staple food of the region, paddy rice (Oryza sativa L.). To determine if this irrigation has led to a buildup of arsenic levels in paddy fields, and the consequences for arsenic exposure through rice ingestion, a survey of arsenic levels in paddy soils and rice grain was undertaken. Survey of paddy soils throughout Bangladesh showed that arsenic levels were elevated in zones where arsenic in groundwater used for irrigation was high, and where these tube-wells have been in operation for the longest period of time. Regression of soil arsenic levels with tube-well age was significant. Arsenic levels reached 46 microg g(-1) dry weight in the most affected zone, compared to levels below l0 microg g(-1) in areas with low levels of arsenic in the groundwater. Arsenic levels in rice grain from an area of Bangladesh with low levels of arsenic in groundwaters and in paddy soils showed that levels were typical of other regions of the world. Modeling determined, even these typical grain arsenic levels contributed considerably to arsenic ingestion when drinking water contained the elevated quantity of 0.1 mg L(-1). Arsenic levels in rice can be further elevated in rice growing on arsenic contaminated soils, potentially greatly increasing arsenic exposure of the Bangladesh population. Rice grain grown in the regions where arsenic is building up in the soil had high arsenic concentrations, with three rice grain samples having levels above 1.7 microg g(-1). PMID:12564892

  11. Linking Microbial Activity with Arsenic Fate during Cow Dung Disposal of Arsenic-Bearing Wastes

    NASA Astrophysics Data System (ADS)

    Clancy, T. M.; Reddy, R.; Tan, J.; Hayes, K. F.; Raskin, L.

    2014-12-01

    To address widespread arsenic contamination of drinking water sources numerous technologies have been developed to remove arsenic. All technologies result in the production of an arsenic-bearing waste that must be evaluated and disposed in a manner to limit the potential for environmental release and human exposure. One disposal option that is commonly recommended for areas without access to landfills is the mixing of arsenic-bearing wastes with cow dung. These recommendations are made based on the ability of microorganisms to create volatile arsenic species (including mono-, di-, and tri-methylarsine gases) to be diluted in the atmosphere. However, most studies of environmental microbial communities have found only a small fraction (<0.1 %) of the total arsenic present in soils or rice paddies is released via volatilization. Additionally, past studies often have not monitored arsenic release in the aqueous phase. Two main pathways for microbial arsenic volatilization are known and include methylation of arsenic during methanogenesis and methylation by arsenite S-adenosylmethionine methyltransferase. In this study, we compare the roles of these two pathways in arsenic volatilization and aqueous mobilization through mesocosm experiments with cow dung and arsenic-bearing wastes produced during drinking water treatment in West Bengal, India. Arsenic in gaseous, aqueous, and solid phases was measured. Consistent with previous reports, less than 0.02% of the total arsenic present was volatilized. A much higher amount (~5%) of the total arsenic was mobilized into the liquid phase. Through the application of molecular tools, including 16S rRNA sequencing and quantification of gene transcripts involved in methanogenesis, this study links microbial community activity with arsenic fate in potential disposal environments. These results illustrate that disposal of arsenic-bearing wastes by mixing with cow dung does not achieve its end goal of promoting arsenic volatilization

  12. System for removal of arsenic from water

    DOEpatents

    Moore, Robert C.; Anderson, D. Richard

    2004-11-23

    Systems 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 systems 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 system for continuous removal of arsenic from water is provided. Also provided is a system for concentrating arsenic in a water sample to facilitate quantification of arsenic, by means of magnesium or calcium hydroxide adsorption.

  13. Arsenic for the fool: an exponential connection.

    PubMed

    Dani, Sergio U

    2010-03-15

    Anthropogenic arsenic is insidiously building up together with natural arsenic to a level unprecedented in the history of mankind. Arsenopyrite (FeAsS) is the principal ore of arsenic and gold in hard rock mines; it is formed by a coupled substitution of sulphur by arsenic in the structure of pyrite (FeS(2)) - nicknamed "fool's gold". Other important sources of anthropogenic arsenic are fossil fuels such as coal and oil. Here I report on the first indication that the environmental concentration of total arsenic in topsoils - in the 7-18ppm range - is exponentially related to the prevalence and mortality of Alzheimer's disease and other dementias in European countries. This evidence defies the imputed absence of verified cases of human morbidity or mortality resulting from exposure to low-level arsenic in topsoils. PMID:20123147

  14. Managing hazardous pollutants in Chile: arsenic.

    PubMed

    Sancha, Ana María; O'Ryan, Raul

    2008-01-01

    Chile is one of the few countries that faces the environmental challenge posed by extensive arsenic pollution, which exists in the northern part of the country. Chile has worked through various options to appropriately address the environmental challenge of arsenic pollution of water and air. Because of cost and other reasons, copying standards used elsewhere in the world was not an option for Chile. Approximately 1.8 million people, representing about 12% of the total population of the country, live in arsenic-contaminated areas. In these regions, air, water, and soil are contaminated with arsenic from both natural and anthropogenic sources. For long periods, water consumed by the population contained arsenic levels that exceeded values recommended by the World Health Organization. Exposure to airborne arsenic also occurred near several large cities, as a consequence of both natural contamination and the intensive mining activity carried out in those areas. In rural areas, indigenous populations, who lack access to treated water, were also exposed to arsenic by consuming foods grown locally in arsenic-contaminated soils. Health effects in children and adults from arsenic exposure first appeared in the 1950s. Such effects included vascular, respiratory, and skin lesions from intake of high arsenic levels in drinking water. Methods to remove arsenic from water were evaluated, developed, and implemented that allowed significant reductions in exposure at a relatively low cost. Construction and operation of treatment plants to remove arsenic from water first began in the 1970s. Beginning in the 1990s, epidemiological studies showed that the rate of lung and bladder cancer in the arsenic-polluted area was considerably higher than mean cancer rates for the country. Cancer incidence was directly related to arsenic exposure. During the 1990s, international pressure and concern by Chile's Health Ministry prompted action to regulate arsenic emissions from copper smelters. A

  15. Evaluation of Arsenic Removal Technology: Arsenic Demonstration Program

    EPA Science Inventory

    Specific objectives of this program are to evaluate the reliability of the arsenic technologies of small scale systems; to gauge the simplicity of system operations, maintenance and operator skill; to determine the cost-effectiveness of the treatment technologies; and to characte...

  16. Arsenic silicide formation by oxidation of arsenic implanted silicon

    NASA Astrophysics Data System (ADS)

    Hagmann, D.; Euen, W.; Schorer, G.; Metzger, G.

    1989-07-01

    Wet oxidations of (100) silicon implanted with an arsenic dose of 2 × 1016 cm-2 and an energy of 30 keV were carried out in the temperature range between 600 and 900° C. The oxidation rate is increased on the arsenic implanted samples up to a factor of 2000 as compared to undoped samples. During these oxidations the arsenic suicide phase AsSi is precipitated at the oxide/silicon interface. After short oxidation times at 600° C, a continuous AsSi layer is found. It is dissolved during extended oxidation times and finally almost all As is incorporated in the oxide. After 900° C oxidations, substantial AsSi crystallites remain at the Si/SiO2 interface. They are still observed up to the larg-est oxide thickness grown (2.3 µm). The AsSi phase and the distribution of the im-planted arsenic were analyzed by TEM, SIMS and XRF measurements.

  17. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  18. [Anticancer propaganda: myth or reality?].

    PubMed

    Demin, E V; Merabishvili, V M

    2014-01-01

    The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer. PMID:24772625

  19. A systematic study of neutral and charged 3d-metal trioxides and tetraoxides

    NASA Astrophysics Data System (ADS)

    Pradhan, Kalpataru; Gutsev, Gennady L.; Weatherford, Charles A.; Jena, Purusottam

    2011-04-01

    Using density functional theory with generalized gradient approximation, we have performed a systematic study of the structure and properties of neutral and charged trioxides (MO3) and tetraoxides (MO4) of the 3d-metal atoms. The results of our calculations revealed a number of interesting features when moving along the 3d-metal series. (1) Geometrical configurations of the lowest total energy states of neutral and charged trioxides and tetraoxides are composed of oxo and/or peroxo groups, except for CuO3- and ZnO3- which possess a superoxo group, CuO4+ and ZnO4+ which possess two superoxo groups, and CuO3+, ZnO3+, and ZnO4- which possess an ozonide group. While peroxo groups are found in the early and late transition metals, all oxygen atoms bind chemically to the metal atom in the middle of the series. (2) Attachment or detachment of an electron to/from an oxide often leads to a change in the geometry. In some cases, two dissociatively attached oxygen atoms combine and form a peroxo group or a peroxo group transforms into a superoxo group and vice versa. (3) The adiabatic electron affinity of as many as two trioxides (VO3 and CoO3) and four tetraoxides (TiO4, CrO4, MnO4, and FeO4) are larger than the electron affinity of halogen atoms. All these oxides are hence superhalogens although only VO3 and MnO4 satisfy the general superhalogen formula.

  20. A systematic study of neutral and charged 3d-metal trioxides and tetraoxides.

    PubMed

    Pradhan, Kalpataru; Gutsev, Gennady L; Weatherford, Charles A; Jena, Purusottam

    2011-04-14

    Using density functional theory with generalized gradient approximation, we have performed a systematic study of the structure and properties of neutral and charged trioxides (MO(3)) and tetraoxides (MO(4)) of the 3d-metal atoms. The results of our calculations revealed a number of interesting features when moving along the 3d-metal series. (1) Geometrical configurations of the lowest total energy states of neutral and charged trioxides and tetraoxides are composed of oxo and∕or peroxo groups, except for CuO(3)(-) and ZnO(3)(-) which possess a superoxo group, CuO(4)(+) and ZnO(4)(+) which possess two superoxo groups, and CuO(3)(+), ZnO(3)(+), and ZnO(4)(-) which possess an ozonide group. While peroxo groups are found in the early and late transition metals, all oxygen atoms bind chemically to the metal atom in the middle of the series. (2) Attachment or detachment of an electron to∕from an oxide often leads to a change in the geometry. In some cases, two dissociatively attached oxygen atoms combine and form a peroxo group or a peroxo group transforms into a superoxo group and vice versa. (3) The adiabatic electron affinity of as many as two trioxides (VO(3) and CoO(3)) and four tetraoxides (TiO(4), CrO(4), MnO(4), and FeO(4)) are larger than the electron affinity of halogen atoms. All these oxides are hence superhalogens although only VO(3) and MnO(4) satisfy the general superhalogen formula. PMID:21495753

  1. Self-assembled flower-like antimony trioxide microstructures with high infrared reflectance performance

    SciTech Connect

    Ge, Shengsong; Yang, Xiaokun; Shao, Qian; Liu, Qingyun; Wang, Tiejun; Wang, Lingyun; Wang, Xiaojie

    2013-04-15

    A simple hydrothermal process was adopted to self-assembly prepare high infrared reflective antimony trioxide with three-dimensional flower-like microstructures. The morphologies of antimony trioxide microstructures were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high resolution transmission electron microscopy (HRTEM) respectively. It is also found that experimental parameters, such as NaOH concentration, surfactant concentration and volume ratio of ethanol–water played crucial roles in controlling the morphologies of Sb{sub 2}O{sub 3} microstructures. A possible growth mechanism of flower-like Sb{sub 2}O{sub 3} microstructure was proposed based on the experimental data. UV–vis–NIR spectra verified that the near infrared reflectivity of the obtained flower-like microstructures could averagely achieve as 92% with maximum reflectivity of 98%, obviously higher than that of other different morphologies of antimony trioxide microstructures. It is expected that the flower-like Sb{sub 2}O{sub 3} nanostructures have some applications in optical materials and heat insulation coatings. - Graphical abstract: Flower-like Sb{sub 2}O{sub 3} microstructures that composed of nanosheets with thickness of ca. 100 nm exhibit high reflectivity under UV–vis–NIR spectra. Highlights: ► Uniform flower-like microstructures were synthesized via simple hydrothermal reaction. ► The flower-like Sb{sub 2}O{sub 3} microstructures exhibited higher reflectivity than other morphologies under the UV–vis–NIR light. ► Influencing parameters on the Sb{sub 2}O{sub 3} morphologies have been discussed in detail. ► Possible mechanism leading to flower-like microstructures was proposed.

  2. Polymerization of aniline in the interlayer space of molybdenum trioxide and its electrochemical properties

    SciTech Connect

    Li Yanping; Xiang Yixian; Dong Xiaowen; Xu Jiaqiang; Ruan Fei; Pan Qingyi

    2009-08-15

    Molybdenum trioxide/polyaniline (MoO{sub 3}/PANI) composite was prepared first by ion-exchange reaction between aniline (ANI) and dodecylamine (DDA) which was intercalated precursor, and then was formed under the polymerization of ANI within the interlayer space of MoO{sub 3} at 120 deg. C for 3 d in air. According to powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, infrared spectroscopy and electrochemical testing, MoO{sub 3}/PANI composite has layered structure, and its interlayer spacing is 1.127 nm. Moreover, it has high thermal stability with the compound and completes its weight loss at 751.9 deg. C. Electrochemical investigation shows that MoO{sub 3} is the major active substance in the MoO{sub 3}/PANI electrode, and MoO{sub 3}/PANI electrode demonstrates better conductivity and electrochemical activity than pure MoO{sub 3} electrode, attributed to the promotion of Li{sup +} and/or electron transport. In addition, the alternating current impedance proves that if the resistance of MoO{sub 3}/PANI electrode reduces apparently, the electrochemical activity will increase correspondingly, the same as the relationship between the ohmic resistance and the electrical conductivity. - Graphical abstract: Aniline (ANI) monomer was intercalated into the interlayer space of molybdenum trioxide (MoO{sub 3}) and heat-treated at 120 deg. C for 3 d in air, and then polymerized to form layered structure of molybdenum trioxide/polyaniline (MoO{sub 3}/PANI) composite. Its interlayer spacing of MoO{sub 3}/PANI composite is 1.127 nm.

  3. Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

    SciTech Connect

    Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. )

    1989-11-01

    In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

  4. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse

    PubMed Central

    Pachauri, Vidhu; Flora, SJS

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study. PMID:26339189

  5. ARSENIC EXPOSURE STUDY, WASHINGTON STATE

    EPA Science Inventory

    The Port Gamble SKlallam tribe has requested that the US Environmental Protection Agency assist them in understanding their exposures to arsenic from both food and water. A previous study has suggested that locally harvested shellfish which are a component of their diet contain ...

  6. Bimetallic nanoparticles for arsenic detection.

    PubMed

    Moghimi, Nafiseh; Mohapatra, Mamata; Leung, Kam Tong

    2015-06-01

    Effective and sensitive monitoring of heavy metal ions, particularly arsenic, in drinking water is very important to risk management of public health. Arsenic is one of the most serious natural pollutants in soil and water in more than 70 countries in the world. The need for very sensitive sensors to detect ultralow amounts of arsenic has attracted great research interest. Here, bimetallic FePt, FeAu, FePd, and AuPt nanoparticles (NPs) are electrochemically deposited on the Si(100) substrate, and their electrochemical properties are studied for As(III) detection. We show that trace amounts of As(III) in neutral pH could be determined by using anodic stripping voltammetry. The synergistic effect of alloying with Fe leads to better performance for Fe-noble metal NPs (Au, Pt, and Pd) than pristine noble metal NPs (without Fe alloying). Limit of detection and linear range are obtained for FePt, FeAu, and FePd NPs. The best performance is found for FePt NPs with a limit of detection of 0.8 ppb and a sensitivity of 0.42 μA ppb(-1). The selectivity of the sensor has also been tested in the presence of a large amount of Cu(II), as the most detrimental interferer ion for As detection. The bimetallic NPs therefore promise to be an effective, high-performance electrochemical sensor for the detection of ultratrace quantities of arsenic. PMID:25938763

  7. Mineral trioxide aggregate (MTA) apexification: a novel approach for traumatised young immature permanent teeth

    PubMed Central

    Vijayran, Manisha; Chaudhary, Seema; Manuja, Naveen; Kulkarni, Adwait Uday

    2013-01-01

    Here, we report a case of 9-year-old boy who came with a chief complaint of pain and fractured upper front teeth. Significant history of trauma was revealed 6 months before reporting, during playing at his school time. Proper diagnosis was made with the help of radiological investigations. The available treatment options were discussed with the patient's parents and root canal therapy, using mineral trioxide aggregate, as an apical barrier was carried out in his upper right front teeth. However, later on, the boy was aesthetically rehabilitated in relation to his fractured upper front teeth with the help of post and core and acrylic crown. PMID:23314456

  8. Photoelectrochemical and physical properties of tungsten trioxide films obtained by aerosol pyrolysis

    SciTech Connect

    Sadale, S.B.; Chaqour, S.M.; Gorochov, O.; Neumann-Spallart, M.

    2008-06-03

    Aerosol pyrolysis (AP) was used for preparing semiconducting films of tungsten trioxide using peroxotungstic acid as a precursor. The films were characterized by SEM, XRD, and by their photoelectrochemical response. Porous, polycrystalline (monoclinic) films of thickness up to 3 {mu}m were prepared. An incident photon to current efficiency (IPCE) of 0.55 at 365 nm was obtained for films of 1 {mu}m thickness on conducting F:SnO{sub 2}/glass substrates under depletion conditions, in junctions with aqueous electrolytes. The spectral (photocurrent) response extended into the visible region (up to 470 nm) which is of importance for solar applications like photocatalysis.

  9. Nanostructures of crystalline molybdenum trioxide grown by condensation in a carrier gas.

    PubMed

    Diaz-Droguett, D E; Fuenzalida, V M; Solorzano, G

    2008-11-01

    Molybdenum trioxide nanostructures were grown by direct evaporation of MoO3 from a tungsten boat resistively heated in the presence of hydrogen or helium as carrier gas at pressures from 100 to 600 Pa. Crystalline structures such as, nanoribbons, nanofibers, nanoneedles and nanoparticles were obtained at source temperatures below 900 degrees C. On the other hand, at source temperatures above 1000 degrees C, nanoporous structures were obtained. The latter were found more often when hydrogen was used as carrier gas. PMID:19198335

  10. Enhanced water splitting at thin film tungsten trioxide photoanodes bearing plasmonic gold-polyoxometalate particles.

    PubMed

    Solarska, Renata; Bienkowski, Krzysztof; Zoladek, Sylwia; Majcher, Aldona; Stefaniuk, Tomasz; Kulesza, Pawel J; Augustynski, Jan

    2014-12-15

    Tungsten trioxide (WO3) is one of a few stable semiconductor materials liable to produce solar fuel by photoelectrochemical water splitting. To enhance its visible light conversion efficiency, we incorporated plasmonic gold nanoparticles (Au NPs) derivatized with polyoxometalate (H3PMo12O40) species into WO3. The combined plasmonic and catalytic effect of Au NPs anchored to the WO3 surface resulted in a large increase of water photooxidation currents. Shielding the Au NPs with polyoxometalates appears to be an effective means to avoid formation of recombination centers at the photoanode surface. PMID:25332175

  11. Determination of arsenic compounds in earthworms

    SciTech Connect

    Geiszinger, A.; Goessler, W.; Kuehnelt, D.; Kosmus, W.; Francesconi, K.

    1998-08-01

    Earthworms and soil collected from six sites in Styria, Austria, were investigated for total arsenic concentrations by ICP-MS and for arsenic compounds by HPLC-ICP-MS. Total arsenic concentrations ranged from 3.2 to 17.9 mg/kg dry weight in the worms and from 5.0 to 79.7 mg/kg dry weight in the soil samples. There was no strict correlation between the total arsenic concentrations in the worms and soil. Arsenic compounds were extracted from soil and a freeze-dried earthworm sample with a methanol/water mixture (9:1, v/v). The extracts were evaporated to dryness, redissolved in water, and chromatographed on an anion- and a cation-exchange column. Arsenic compounds were identified by comparison of the retention times with known standards. Only traces of arsenic acid could be extracted from the soil with the methanol/water (9:1, v/v) mixture. The major arsenic compounds detected in the extracts of the earthworms were arsenous acid and arsenic acid. Arsenobetaine was present as a minor constituent, and traces of dimethylarsinic acid were also detected. Two dimethylarsinoyltribosides were also identified in the extracts by co-chromatography with standard compounds. This is the first report of the presence of dimethylarsinoylribosides in a terrestrial organism. Two other minor arsenic species were present in the extract, but their retention times did not match with the retention times of the available standards.

  12. Arsenic species in poultry feather meal.

    PubMed

    Nachman, K E; Raber, G; Francesconi, K A; Navas-Acien, A; Love, D C

    2012-02-15

    Organoarsenical drugs are widely used in the production of broiler chickens in the United States. Feathers from these chickens are processed into a meal product that is used as an animal feed additive and as an organic fertilizer. Research conducted to date suggests that arsenical drugs, specifically roxarsone, used in poultry production result in the accumulation of arsenic in the keratinous material of poultry feathers. The use of feather meal product in the human food system and in other settings may result in human exposures to arsenic. Consequently, the presence and nature of arsenic in twelve samples of feather meal product from six US states and China were examined. Since arsenic toxicity is highly species-dependent, speciation analysis using HPLC/ICPMS was performed to determine the biological relevance of detected arsenic. Arsenic was detected in all samples (44-4100 μg kg(-1)) and speciation analyses revealed that inorganic forms of arsenic dominated, representing 37 - 83% of total arsenic. Roxarsone was not detected in the samples (<20 μg As kg(-1)). Feather meal products represent a previously unrecognized source of arsenic in the food system, and may pose additional risks to humans as a result of its use as an organic fertilizer and when animal waste is managed. PMID:22244353

  13. Health Effects of Chronic Arsenic Exposure

    PubMed Central

    Hong, Young-Seoub; Song, Ki-Hoon; Chung, Jin-Yong

    2014-01-01

    Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments. PMID:25284195

  14. Arsenic removal from drinking water during coagulation

    SciTech Connect

    Hering, J.G.; Chen, P.Y.; Wilkie, J.A.; Elimelech, M.

    1997-08-01

    The efficiency of arsenic removal from source waters and artificial freshwaters during coagulation with ferric chloride and alum was examined in bench-scale studies. Arsenic(V) removal by either ferric chloride or alum was relatively insensitive to variations in source water composition below pH 8. At pH 8 and 9, the efficiency of arsenic(V) removal by ferric chloride was decreased in the presence of natural organic matter. The pH range for arsenic(V) removal with alum was more restricted than with ferric chloride. For source waters spiked with 20 {micro}g/L arsenic(V), final dissolved arsenic(V) concentrations in the product water of less than 2 {micro}g/L were achieved with both coagulants at neutral pH. Removal of arsenic(III) from source waters by ferric chloride was both less efficient and more strongly influenced by source water composition than removal of arsenic(V). The presence of sulfate (at pH 4 and 5) and natural organic matter (at pH 4 through 9) adversely affected the efficiency of arsenic(III) removal by ferric chloride. Arsenic(III) could not be removed from source waters by coagulation with alum.

  15. Chapter4: Toxicology and Epidemiology of Arsenic and its Compounds

    EPA Science Inventory

    Arsenic poses numerous environmental challenges, especially in the groundwater of Bangladesh and other developing nations. As a metalloid, arsenic has the properties of both a metal and a nonmetal. In organisms, metabolism of arsenic consists ofcomplex and multiple reduction and ...

  16. Arsenic in Drinking Water-A Global Environmental Problem

    ERIC Educational Resources Information Center

    Wang, Joanna Shaofen; Wai, Chien M.

    2004-01-01

    Information on the worldwide occurrence of groundwater pollution by arsenic, the ensuing health hazards, and the debatable government regulations of arsenic in drinking water, is presented. Diagnostic identification of arsenic, and methods to eliminate it from water are also discussed.

  17. Arsenic chemistry in soils and sediments

    SciTech Connect

    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 dissolved

  18. Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia.

    PubMed

    Jiang, Hao; Liang, Gong-Wen; Huang, Xiao-Jun; Jiang, Qian; Han, Sheng; Shi, Lu-Wen; Zhu, Hong-Hu

    2015-12-01

    We have demonstrated that oral arsenic (Realgar-Indigo naturalis formula, RIF) plus all-trans retinoic acid (ATRA) is not inferior to intravenous arsenic trioxide (ATO) plus ATRA as the first-line treatment of acute promyelocytic leukemia (APL). To compare the cost-effectiveness of oral and intravenous arsenic, we analyzed the results of 30 patients in each group involved in a randomized controlled trial at our center. The median total medical costs were $13,183.49 in the RIF group compared with $24136.98 in the ATO group (p<0.0001). This difference primarily resulted from the different costs of induction therapy (p=0.016) and maintenance treatment (p<0.0001). The length of hospitalization for the RIF group was significantly lower than that for the ATO group (24 vs. 31 days, p<0.0001) during induction therapy. During maintenance treatment, the estimated medical costs were $2047.14 for each patient in the RIF group treated at home compared with $11273.81 for each patient in the ATO group treated in an outpatient setting (p<0.0001). We conclude that oral RIF plus ATRA significantly reduced the medical costs and length of hospital stay during induction and remission therapy compared with ATO plus ATRA in APL patients. PMID:26403986

  19. ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE INORGANIC ARSENIC METHYLATION PHENOTYPE

    EPA Science Inventory

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidence suggest that some of the adverse health effects associated with chronic exposure to in...

  20. ARSENIC INTERACTION WITH IRON (II, III) HYDROXYCARBONATE GREEN RUST: IMPLICATIONS FOR ARSENIC REMEDIATION

    EPA Science Inventory

    Zerovalent iron is being used in permeable reactive barriers (PRBs) to remediate groundwater arsenic contamination. Iron(II, III) hydroxycarbonate green rust is a major corrosion product of zerovalent iron under anaerobic conditions. The interaction between arsenic and this green...

  1. Plant Antimicrobial Peptides as Potential Anticancer Agents

    PubMed Central

    Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy. PMID:25815333

  2. Role of Metabolism in Arsenic-Induced Toxicity: Identification and Quantification of Arsenic Metabolites in Tissues and Excreta

    EPA Science Inventory

    Arsenic is a known toxicant and carcinogen. Methylation of inorganic arsenic was once thought to be a detoxification mechanism because of the rapid excretion and relatively lower toxicity of the pentavalent organic arsenical metabolites. Advances in analytical chemistry have al...

  3. Arsenic-resistant bacteria solubilized arsenic in the growth media and increased growth of arsenic hyperaccumulator Pteris vittata L.

    PubMed

    Ghosh, Piyasa; Rathinasabapathi, Bala; Ma, Lena Q

    2011-10-01

    The role of arsenic-resistant bacteria (ARB) in arsenic solubilization from growth media and growth enhancement of arsenic-hyperaccumulator Pteris vittata L. was examined. Seven ARB (tolerant to 10 mM arsenate) were isolated from the P. vittata rhizosphere and identified by 16S rRNA sequencing as Pseudomonas sp., Comamonas sp. and Stenotrophomonas sp. During 7-d hydroponic experiments, these bacteria effectively solubilized arsenic from the growth media spiked with insoluble FeAsO₄ and AlAsO₄ minerals (from < 5 μg L⁻¹ to 5.04-7.37 mg L⁻¹ As) and enhanced plant arsenic uptake (from 18.1-21.9 to 35.3-236 mg kg⁻¹ As in the fronds). Production of (1) pyochelin-type siderophores by ARB (fluorescent under ultraviolet illumination and characterized with thin layer chromatography) and (2) root exudate (dissolved organic C) by P. vittata may be responsible for As solubilization. Increase in P. vittata root biomass from 1.5-2.2 to 3.4-4.2 g/plant dw by ARB and by arsenic was associated with arsenic-induced plant P uptake. Arsenic resistant bacteria may have potential to enhance phytoremediation of arsenic-contaminated soils by P. vittata. PMID:21840210

  4. Anticancer agent-based marine natural products and related compounds.

    PubMed

    Chen, Jian-Wei; Wu, Qi-Hao; Rowley, David C; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed. PMID:25559315

  5. DETERMINATION OF ARSENIC AND ARSENICALS IN FOODS AND OTHER BIOLOGICAL MATERIALS

    EPA Science Inventory

    An extensive review is presented on methodology for the determination of arsenic and its compounds. The review includes collection and storage of samples and sample preparation for (a) determination of total arsenic content and (b) of specific arsenic compounds. A section covers ...

  6. Method of arsenic removal from water

    DOEpatents

    Gadgil, Ashok

    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.

  7. Carcinogenic, teratogenic, and mutagenic effects of arsenic.

    PubMed Central

    Bencko, V

    1977-01-01

    This review outlines briefly the history and present status of the problem of carcinogenic, teratogenic and mutagenic effects of arsenic. Discrepancies between clinical observations and positive results of epidemiological studies and the experimental induction of cancer by arsenic are discussed. The present knowledge of the mechanism of teratogenic and mutagenic effects of arsenic is analyzed. The growing importance of arsenic as an environmental pollutant is demonstrated. Continuation of throughly organized epidemiological studies in regions with excessive arsenic exposure of the population and standardization of an epidemiological approach to this problem on an international basis are recommended. New approaches in experimental studies of the carcinogenicity of arsenic in combination with other known or suspected carcinogens are recommended as well. PMID:908296

  8. Correlation of electrochromic properties and oxidation states in nanocrystalline tungsten trioxide.

    PubMed

    Darmawi, S; Burkhardt, S; Leichtweiss, T; Weber, D A; Wenzel, S; Janek, J; Elm, M T; Klar, P J

    2015-06-28

    Although tungsten trioxide (WO3) has been extensively studied since its electrochromic properties were first discovered, the mechanism responsible for the coloration or bleaching effect is still disputed. New insights into the coloration mechanism of electrochromic, nanocrystalline WO3 are provided in this paper by studying thin WO3 films combining the electrochemical and spectroscopic techniques. By employing in situ UV-Vis transmission spectroscopy at a fixed spectral band pass during electrochemical experiments, such as cyclic voltammetry, a two-step insertion process for both protons and lithium ions is identified, of which one step exhibits a significantly higher coloration efficiency than the other. To obtain a better understanding of the insertion process AxWO3 (A = H, Li,…) thin films were studied at different stages of intercalation using UV-Vis and X-ray photoelectron spectroscopy. The results show that the first step of the intercalation process represents the reduction from initial W(6+) to W(5+) and the second step the reduction of W(5+) to W(4+). We found that the blue coloration of this nanocrystalline tungsten trioxide is mainly due to the presence of W(4+) rather than that of W(5+). PMID:26018838

  9. Capping a Pulpotomy with Calcium Aluminosilicate Cement: Comparison to Mineral Trioxide Aggregates

    PubMed Central

    Kramer, Phillip R.; Woodmansey, Karl F.; White, Robert; Primus, Carolyn M.; Opperman, Lynne A.

    2014-01-01

    Introduction Calcium aluminate cements have shown little affinity for bacterial growth, low toxicity, and immunogenicity when used as a restoration material, but calcium aluminate cements have not been tested in vivo in pulpotomy procedures. Methods To address this question, a calcium aluminate cement (Quick-Set) was tested along with 2 mineral trioxide aggregates, ProRoot MTA and MTA Plus. These cements were used as a capping agent after pulpotomy. Control rats had no pulpotomy, or the pulpotomy was not capped. Proinflammatory cytokines interleukin (IL)-1β and IL-1α were measured, and histology was performed at 30 and 60 days after capping. The nociceptive response was determined by measuring the lengthening of the rat's meal duration. Results and Conclusions: IL-1β and IL-1α concentrations were reduced in the capped teeth, but no differences were observed among the 3 cements. Dentinal bridging could be detected at both 30 and 60 days with each of the 3 cements, and the pulps were still vital 60 days after capping. Meal duration significantly shortened after placement of the 3 different cements, indicating a nociceptive response, but there were no differences among the materials. Calcium aluminate cements had similar properties to mineral trioxide aggregates and is a viable option for pulpotomy procedures. PMID:25146026

  10. Anticancer Properties of Capsaicin Against Human Cancer.

    PubMed

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities. PMID:26976969

  11. Glutamic acid as anticancer agent: An overview

    PubMed Central

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed. PMID:24227952

  12. Acute arsenic poisoning in two siblings.

    PubMed

    Lai, Melisa W; Boyer, Edward W; Kleinman, Monica E; Rodig, Nancy M; Ewald, Michele Burns

    2005-07-01

    We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy. PMID:15995066

  13. XAS Studies of Arsenic in the Environment

    SciTech Connect

    Charnock, J. M.; Polya, D. A.; Gault, A. G.; Morgan, A. J.

    2007-02-02

    Arsenic is present in low concentrations in much of the Earth's crust and changes in its speciation are vital to understanding its transport and toxicity in the environment. We have used X-ray absorption spectroscopy to investigate the coordination sites of arsenic in a wide variety of samples, including soil and earthworm tissues from arsenic-contaminated land, and human hair and nail samples from people exposed to arsenic in Cambodia. Our results confirm the effectiveness of using X-ray absorption near edge structure (XANES) and X-ray absorption fine structure (EXAFS) spectroscopy to determine speciation changes in environmental samples.

  14. In-tank recirculating arsenic treatment system

    DOEpatents

    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.

  15. Arsenic and Antimony Transporters in Eukaryotes

    PubMed Central

    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. PMID:22489166

  16. The charge and discharge behavior of molybdenum trioxide electrodes in lithium perchlorate-propylene carbonate electrolyte. Technical report

    SciTech Connect

    Hunger, H.F.; Ellison, J.E.

    1980-07-01

    The anodic and cathodic behavior of molybdenum trioxide electrodes in various states of lithiation was investigated in 1M LiClO/sub 4/-PC electrolytes at room temperature. A comparison was made between the anodic and cathodic rate capabilities of the electrodes. From cycling experiments at various depths of discharge, cycle life data were obtained. Problems observed after deep discharges are discussed.

  17. Serendipity in anticancer drug discovery.

    PubMed

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-10

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind. PMID:22247822

  18. Serendipity in anticancer drug discovery

    PubMed Central

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-01

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind. PMID:22247822

  19. Insights into the carcinogenic mode of action of arsenic

    SciTech Connect

    Kligerman, A.D. Tennant, A.H.

    2007-08-01

    That arsenic can induce cancer in humans has been known since the late 17th century, yet how arsenic induces cancer has been the subject of numerous scientific publications. Various modes of action (MOA) have been proposed for arsenic's carcinogenicity. In this paper we review our previous studies on the ability of arsenicals to cause DNA damage, the relative inability of these arsenicals to induce point mutations, and the involvement of arsenicals in spindle disruption. We present new evidence that shows that reduced glutathione (GSH) can chemically reduce inactive pentavalent arsenicals to trivalent arsenicals which can disrupt tubulin polymerization, and show that reactive oxygen species (ROS) are most likely not involved in tubulin disruption. A hypothesis is also presented on how arsenic may induce stable chromosome aberrations (CAs) that can lead to cancer, thus supporting a role for genetic damage in the MOA for arsenic. We then propose promising areas of research that might give insight into the MOA of arsenic.

  20. Clean process to destroy arsenic-containing organic compounds with recovery of arsenic

    DOEpatents

    Upadhye, R.S.; Wang, F.T.

    1996-08-13

    A reduction method is provided for the treatment of arsenic-containing organic compounds with simultaneous recovery of pure arsenic. Arsenic-containing organic compounds include pesticides, herbicides, and chemical warfare agents such as Lewisite. The arsenic-containing compound is decomposed using a reducing agent. Arsine gas may be formed directly by using a hydrogen-rich reducing agent, or a metal arsenide may be formed using a pure metal reducing agent. In the latter case, the arsenide is reacted with an acid to form arsine gas. In either case, the arsine gas is then reduced to elemental arsenic. 1 fig.

  1. Clean process to destroy arsenic-containing organic compounds with recovery of arsenic

    DOEpatents

    Upadhye, Ravindra S.; Wang, Francis T.

    1996-01-01

    A reduction method is provided for the treatment of arsenic-containing organic compounds with simultaneous recovery of pure arsenic. Arsenic-containing organic compounds include pesticides, herbicides, and chemical warfare agents such as Lewisite. The arsenic-containing compound is decomposed using a reducing agent. Arsine gas may be formed directly by using a hydrogen-rich reducing agent, or a metal arsenide may be formed using a pure metal reducing agent. In the latter case, the arsenide is reacted with an acid to form arsine gas. In either case, the arsine gas is then reduced to elemental arsenic.

  2. Arsenic biomethylation by photosynthetic organisms

    PubMed Central

    Ye, Jun; Rensing, Christopher; Rosen, Barry P.; Zhu, Yong-Guan

    2013-01-01

    Arsenic (As) is a ubiquitous element that is widespread in the environment and causes numerous health problems. Biomethylation of As has implications for its mobility and toxicity. Photosynthetic organisms may play a significant role in As geochemical cycling by methylating it to different As species, but little is known about the mechanisms of methylation. Methylated As species have been found in many photosynthetic organisms, and several arsenite S-adenosylmethionine (SAM) methyltransferases have been characterized in cyanobacteria and algae. However, higher plants may not have the ability to methylate As. Instead, methylated arsenicals in plants probably originate from microorganisms in soils and the rhizosphere. Here, we propose possible approaches for developing ‘smart’ photosynthetic organisms with an enhanced and sensitive biomethylation capacity for bioremediation and safer food. PMID:22257759

  3. An evaluation of arsenic release from monolithic solids using a modified semi-dynamic leaching test.

    PubMed

    Dermatas, Dimitris; Moon, Deok Hyun; Menounou, Nektaria; Meng, Xiaoguang; Hires, Richard

    2004-12-10

    Quicklime and quicklime-fly ash-based stabilization/solidification (S/S) effectiveness was evaluated by performing semi-dynamic leaching tests (American Nuclear Society 16.1). Artificial soil samples, contaminated with arsenic trioxide (As2O3) as well as field soil samples contaminated with arsenic (As) were tested. The artificial soils were prepared by mixing amounts of kaolinite or montmorillonite with fine quartz sand. The S/S effectiveness was evaluated by measuring effective diffusion coefficients (De) and leachability indices (LX). Treatment was most effective in kaolinite-based artificial soils treated with quicklime and in quicklime-fly ash treated field soils. The experimental results indicate that De values were lowered as a result of S/S treatment. Upon treatment LX values were higher than 9, suggesting that S/S treated soils are acceptable for "controlled utilization". Based on a model developed by de Groot and van der Sloot [G.J. de Groot, H.A. van der Sloot, in: T.M. Gilliam, C.C. Wiles (Eds.), Stabilization and Solidification of Hazardous, Radioactive, and Mixed Wastes, vol. 2, ASTM STP 1123, ASTM, PA, 1992, p. 149], the leaching mechanism for all of the treated soils was found to be controlled by diffusion. The effect of soluble silica (Si) on As leachability was also evaluated. When soluble Si concentration was less than 1 ppm, As leachability was the lowest. The controlling mechanism of As immobilization whether sorption, precipitation, or inclusion was also evaluated. It was determined that precipitation was the dominant mechanism. PMID:15561360

  4. Arsenic Removal by Liquid Membranes

    PubMed Central

    Marino, Tiziana; Figoli, Alberto

    2015-01-01

    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. PMID:25826756

  5. Impaired arsenic metabolism in children during weaning

    SciTech Connect

    Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro; Grander, Margaretha; Palm, Brita; Vahter, Marie

    2009-09-01

    Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 {mu}g/L, range 2.4-940 {mu}g/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.

  6. Arsenic mobilization and immobilization in paddy soils

    NASA Astrophysics Data System (ADS)

    Kappler, A.; Hohmann, C.; Zhu, Y. G.; Morin, G.

    2010-05-01

    Arsenic is oftentimes of geogenic origin and in many cases bound to iron(III) minerals. Iron(III)-reducing bacteria can harvest energy by coupling the oxidation of organic or inorganic electron donors to the reduction of Fe(III). This process leads either to dissolution of Fe(III)-containing minerals and thus to a release of the arsenic into the environment or to secondary Fe-mineral formation and immobilisation of arsenic. Additionally, aerobic and anaerobic iron(II)-oxidizing bacteria have the potential to co-precipitate or sorb arsenic during iron(II) oxidation at neutral pH that is usually followed by iron(III) mineral precipitation. We are currently investigating arsenic immobilization by Fe(III)-reducing bacteria and arsenic co-precipitation and immobilization by anaerobic iron(II)-oxidizing bacteria in batch, microcosm and rice pot experiments. Co-precipitation batch experiments with pure cultures of nitrate-dependent Fe(II)-oxidizing bacteria are used to quantify the amount of arsenic that can be immobilized during microbial iron mineral precipitation, to identify the minerals formed and to analyze the arsenic binding environment in the precipitates. Microcosm and rice pot experiments are set-up with arsenic-contaminated rice paddy soil. The microorganisms (either the native microbial population or the soil amended with the nitrate-dependent iron(II)-oxidizing Acidovorax sp. strain BoFeN1) are stimulated either with iron(II), nitrate, or oxygen. Dissolved and solid-phase arsenic and iron are quantified. Iron and arsenic speciation and redox state in batch and microcosm experiments are determined by LC-ICP-MS and synchrotron-based methods (EXAFS, XANES).

  7. Arsenic Adsorption Onto Iron Oxides Minerals

    NASA Astrophysics Data System (ADS)

    Aredes, S.; Klein, B.; Pawlik, M.

    2004-12-01

    The predominant form of arsenic in water is as an inorganic ion. Under different redox conditions arsenic in water is stable in the +5 and +3 oxidation states. Arsenic oxidation state governs its toxicity, chemical form and solubility in natural and disturbed environments. As (III) is found in anoxic environments such as ground water , it is toxic and the common species is the neutral form, H3AsO3. As (V) is found in aerobic conditions such as surface water, it is less toxic and the common species in water are: H2AsO4 - and HAsO4 {- 2}. The water pH determines the predominant arsenate or arsenite species, however, both forms of arsenic can be detected in natural water systems. Iron oxides minerals often form in natural waters and sediments at oxic-anoxic boundaries. Over time they undergo transformation to crystalline forms, such as goethite or hematite. Both As(V) and As(III) sorbs strongly to iron oxides, however the sorption behavior of arsenic is dependent on its oxidation state and the mineralogy of the iron oxides. Competition between arsenic and others ions, such fluoride, sulphate and phosphate also play a role. On the other hand, calcium may increase arsenic adsorption onto iron oxides. Electrokinetic studies and adsorption experiments were carried out in order to determine which conditions favour arsenic adsorption. Hematite, goethite and magnetite as iron based sorbents were used. Test were also conducted with a laterite soil rich in iron minerals. The focus of this study is to evaluate physical and chemical conditions which favour arsenic adsorption onto iron oxides minerals, the results contribute to an understanding of arsenic behaviour in natural and disturbed environments. Furthermore, results could contribute in developing an appropriate remediation technology for arsenic removal in water using iron oxides minerals.

  8. ARSENIC REMOVAL AND ECOLOGICALLY SAFE CONTAINMENT OF ARSENIC-WASTE: A SUSTAINABLE SOLUTION FOR ARSENIC CRISIS IN CAMBODIA

    EPA Science Inventory

    An appalling degree of arsenic contamination in groundwater has affected more than a million people in wide region of Mekong delta flood plain in Cambodia. Arsenic is by far the most toxic species of all naturally occurring groundwater contaminants and disposal of removed arse...

  9. A review of recent developments in the speciation and location of arsenic and selenium in rice grain.

    PubMed

    Carey, Anne-Marie; Lombi, Enzo; Donner, Erica; de Jonge, Martin D; Punshon, Tracy; Jackson, Brian P; Guerinot, Mary Lou; Price, Adam H; Meharg, Andrew A

    2012-04-01

    Rice is a staple food yet is a significant dietary source of inorganic arsenic, a class 1, nonthreshold carcinogen. Establishing the location and speciation of arsenic within the edible rice grain is essential for understanding the risk and for developing effective strategies to reduce grain arsenic concentrations. Conversely, selenium is an essential micronutrient and up to 1 billion people worldwide are selenium-deficient. Several studies have suggested that selenium supplementation can reduce the risk of some cancers, generating substantial interest in biofortifying rice. Knowledge of selenium location and speciation is important, because the anti-cancer effects of selenium depend on its speciation. Germanic acid is an arsenite/silicic acid analogue, and location of germanium may help elucidate the mechanisms of arsenite transport into grain. This review summarises recent discoveries in the location and speciation of arsenic, germanium, and selenium in rice grain using state-of-the-art mass spectrometry and synchrotron techniques, and illustrates both the importance of high-sensitivity and high-resolution techniques and the advantages of combining techniques in an integrated quantitative and spatial approach. PMID:22159463

  10. Novel anticancer therapeutics targeting telomerase.

    PubMed

    Ruden, Maria; Puri, Neelu

    2013-08-01

    Telomeres are protective caps at the ends of human chromosomes. Telomeres shorten with each successive cell division in normal human cells whereas, in tumors, they are continuously elongated by human telomerase reverse transcriptase (hTERT). Telomerase is overexpressed in 80-95% of cancers and is present in very low levels or is almost undetectable in normal cells. Because telomerase plays a pivotal role in cancer cell growth it may serve as an ideal target for anticancer therapeutics. Inhibition of telomerase may lead to a decrease of telomere length resulting in cell senescence and apoptosis in telomerase positive tumors. Several strategies of telomerase inhibition are reviewed, including small molecule inhibitors, antisense oligonucleotides, immunotherapies and gene therapies, targeting the hTERT or the ribonucleoprotein subunit hTER. G-quadruplex stabilizers, tankyrase and HSP90 inhibitors targeting telomere and telomerase assembly, and T-oligo approach are also covered. Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001). Most of these agents have entered phase I and II clinical trials in patients with various tumors, and have shown good response rates as evidenced by a reduction in tumor cell growth, increased overall disease survival, disease stabilization in advanced staged tumors and complete/partial responses. Most therapeutics have shown to be more effective when used in combination with standard therapies, resulting in concomitant telomere shortening and tumor mass shrinkage, as well as preventing tumor relapse and resistance to single agent therapy. PMID:22841437

  11. PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia.

    PubMed

    Ohnishi, Kazunori

    2007-10-01

    Acute promyelocytic leukemia (APL) is characterized by generation of the PML-RARalpha fusion gene. PML-RARalpha can homodimerize with another PML-RARalpha, and the hybrid binds the histone-deacetylase recruiting co-repressor complex with higher affinity than the wild-type RARalpha. However, the co-repressor complex is releasable by pharmacological doses of all-trans retinoic acid (ATRA). More than 90% of patients with APL achieve a complete remission (CR) with differentiation therapy consisting of ATRA combined with chemotherapy. A new synthetic retinoid, tamibaroten, showed therapeutic effectiveness in patients with ATRA-resistant APL with increased expression of cellular retinoic acid binding protein (CRABP), and about 60% of patients with relapsed APL achieved a CR. Arsenic trioxide triggers the rapid degradation of PML-RARalpha through the targeting of the PML moieties of the fusion protein and showed a high CR rate in relapsed APL. The combination of ATRA, chemotherapy, and/or new agents improved the long-term survival in patients with APL. PMID:17929112

  12. Vitamin C protects HL60 and U266 cells from arsenic toxicity.

    PubMed

    Karasavvas, Nicos; Cárcamo, Juan M; Stratis, George; Golde, David W

    2005-05-15

    Although there is no compelling evidence that vitamin C has antitumor activity in humans, clinical trials are testing the hypothesis that ascorbic acid (AA) will enhance the efficacy of arsenic trioxide (As2O3) in myeloma. In vitro, AA cytotoxicity depends on its interaction with free transition metal ions in culture media leading to the generation of H2O2 and other reactive oxygen species (ROSs). Therefore, to circumvent the extracellular in vitro pro-oxidant effects of AA, we loaded HL60, U266, and RPMI-8226 cells with vitamin C by incubation with dehydroascorbic acid (DHA). Loading cells in this manner resulted in prominent, dose-dependent protection of As2O3-treated cells as measured by viability, colony formation, and apoptosis assays. Glutathione depletion enhanced cell sensitivity to the cytotoxic effects of As2O3 and vitamin C loading provided protection. AA was found to generate cytotoxic concentrations of H2O2 in culture medium without cells and copper/iron chelators inhibited this reaction. However, AA did not generate H2O2 in simple buffer or human plasma. Direct incubation with AA resulted in increased intracellular ROSs, whereas DHA incubation decreased it. These results clarify an apparent paradox and indicate that vitamin C loading in HL60, U266, and RPMI-8226 cells ameliorates As2O3 cytotoxicity. PMID:15677571

  13. Analysis of six heavy metals in Ortho mineral trioxide aggregate and ProRoot mineral trioxide aggregate by inductively coupled plasma-optical emission spectrometry.

    PubMed

    Kum, Kee-Yeon; Zhu, Qiang; Safavi, Kamran; Gu, Yu; Bae, Kwang-Shik; Chang, Seok Woo

    2013-12-01

    Ortho mineral trioxide aggregate (MTA) is a mineral aggregate newly developed for perforation repair, root end filling and pulp capping. The aim of this study was to investigate the levels of cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni) and zinc (Zn) in Ortho MTA and ProRoot MTA. A total of 0.2 g of each MTA was digested using a mixture of hydrochloric and nitric acids and filtered. Six heavy metals in the resulting filtrates were analyzed by inductively coupled plasma-optical emission spectrometry (n = 5). The results were statistically analyzed using the Mann-Whitney U-test. The concentrations of Cd, Cu, Fe, Mn, Ni and Zn in Ortho MTA were 0.10, 7.73, 49.51, 2.58, 0.82 and 10.09 p.p.m., respectively. The concentrations of Cd, Cu, Fe, Mn, Ni and Zn in ProRoot MTA were 0.16, 9.38, 1438.11, 74.51, 18.98 and 4.05 p.p.m., respectively. In conclusion, Ortho MTA had lower levels of Cd, Cu, Fe, Mn and Ni than ProRoot MTA. PMID:24279659

  14. Engineering the Soil Bacterium Pseudomonas putida for Arsenic Methylation

    PubMed Central

    Chen, Jian; Qin, Jie; Zhu, Yong-Guan; de Lorenzo, Víctor

    2013-01-01

    Accumulation of arsenic has potential health risks through consumption of food. Here, we inserted the arsenite [As(III)] S-adenosylmethionine methyltransferase (ArsM) gene into the chromosome of Pseudomonas putida KT2440. Recombinant bacteria methylate inorganic arsenic into less toxic organoarsenicals. This has the potential for bioremediation of environmental arsenic and reducing arsenic contamination in food. PMID:23645194

  15. 21 CFR 862.3120 - Arsenic test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Arsenic test system. 862.3120 Section 862.3120....3120 Arsenic test system. (a) Identification. An arsenic test system is a device intended to measure arsenic, a poisonous heavy metal, in urine, vomitus, stomach contents, nails, hair, and...

  16. 21 CFR 862.3120 - Arsenic test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Arsenic test system. 862.3120 Section 862.3120....3120 Arsenic test system. (a) Identification. An arsenic test system is a device intended to measure arsenic, a poisonous heavy metal, in urine, vomitus, stomach contents, nails, hair, and...

  17. 21 CFR 862.3120 - Arsenic test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Arsenic test system. 862.3120 Section 862.3120....3120 Arsenic test system. (a) Identification. An arsenic test system is a device intended to measure arsenic, a poisonous heavy metal, in urine, vomitus, stomach contents, nails, hair, and...

  18. 21 CFR 862.3120 - Arsenic test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Arsenic test system. 862.3120 Section 862.3120....3120 Arsenic test system. (a) Identification. An arsenic test system is a device intended to measure arsenic, a poisonous heavy metal, in urine, vomitus, stomach contents, nails, hair, and...

  19. 21 CFR 862.3120 - Arsenic test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Arsenic test system. 862.3120 Section 862.3120....3120 Arsenic test system. (a) Identification. An arsenic test system is a device intended to measure arsenic, a poisonous heavy metal, in urine, vomitus, stomach contents, nails, hair, and...

  20. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 6 2012-07-01 2012-07-01 false Inorganic arsenic. 1910.1018 Section 1910.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS (CONTINUED) Toxic and Hazardous Substances § 1910.1018 Inorganic arsenic. (a) Scope...

  1. METHYLATED TRIVALENT ARSENIC SPECIES ARE GENOTOXIC

    EPA Science Inventory

    ABSTRACT

    The genotoxic effects of arsenic compounds are generally believed to result from other than direct interacton with DNA. The reactivties of methyloxarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled X174 RFI ...

  2. ARSENIC MODEL DEVELOPMENT FOR IMPROVED RISK ASSESSMENT

    EPA Science Inventory

    This project integrates research on the kinetic behavior and metabolism of arsenic at both the cellular and whole organism levels using a physiologically based pharmacokinetic (PBPK) modeling approach. The ultimate goal is development of a robust human PBPK model for arsenic met...

  3. REACTION PROCESSES OF ARSENIC IN SULFIDIC SOLUTIONS

    EPA Science Inventory

    The fate of arsenic in the environment is fundamentally linked to its speciation. Arsenic in aerobic environments is predominantly arsenate, however under reducing conditions arsenite species dominate. In anoxic or sulfidic environments thioarsenite ((As(OH)x(SH)yz-) species alon...

  4. DRINKING WATER ARSENIC AND PERINATAL OUTCOMES

    EPA Science Inventory

    Drinking Water Arsenic and Perinatal Outcomes
    DT Lobdell, Z Ning, RK Kwok, JL Mumford, ZY Liu, P Mendola

    Many studies have documented an association between drinking water arsenic (DWA) and cancer, vascular diseases, and dermatological outcomes, but few have investigate...

  5. Remote Sensing of Arsenic Toxicity in Spinach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arsenic (As) contamination of soil is a critical human health issue. Traditional methods of determining the presence and extent of As contamination focus largely on tedious and expensive soil sampling. Remote sensing of plant tissue may provide a practical alternative to detect arsenic contaminati...

  6. Urinary excretion of arsenic following rice consumption.

    PubMed

    Meharg, A A; Williams, P N; Deacon, C M; Norton, G J; Hossain, M; Louhing, D; Marwa, E; Lawgalwi, Y; Taggart, M; Cascio, C; Haris, P

    2014-11-01

    Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis. PMID:25145278

  7. Arsenic Consumption in the United States.

    PubMed

    Wilson, Denise

    2015-10-01

    Exposure limits for arsenic in drinking water and minimal risk levels (MRLs) for total dietary exposure to arsenic have long been established in the U.S. Multiple studies conducted over the last five years have detected arsenic in foods and beverages including juice, rice, milk, broth (beef and chicken), and others. Understanding whether or not each of these foods or drinks is a concern to certain groups of individuals requires examining which types of and how much arsenic is ingested. In this article, recent studies are reviewed and placed in the context of consumption patterns. When single sources of food or drink are considered in isolation, heavy rice eaters can be exposed to the most arsenic among adults while infants consuming formula containing contaminated organic brown rice syrup are the most exposed group among children. Most food and drink do not contain sufficient arsenic to exceed MRLs. For individuals consuming more than one source of contaminated water or food, however, adverse health effects are more likely. In total, recent studies on arsenic contamination in food and beverages emphasize the need for individual consumers to understand and manage their total dietary exposure to arsenic. PMID:26591332

  8. The Chemistry and Metabolism of Arsenic

    EPA Science Inventory

    I. IntrodctionA century of study of the process by which many organisms convert inorganic arsenic into an array of methylated metabolites has answered many questions and has posed some new ones. The capacity of microorganisms to. form volatile arsenic compounds was first recogniz...

  9. Questions and Answers: Apple Juice and Arsenic

    MedlinePlus

    ... This could be due to different amounts of arsenic in orchard soils. Testing a small number of samples of different ... organic apples come from trees that grow in soil that may contain arsenic. The FDA is not aware of any data ...

  10. Arsenic and human health effects: A review.

    PubMed

    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. PMID:26476885

  11. Tracking the pathway of arsenic metabolism

    EPA Science Inventory

    Although the toxic and carcinogenic properties of arsenic have been recognized for centuries, only in the past few decades has research focused on understanding the metabolic fate of arsenic in humans and relating metabolism to adverse health effects. In humans, conversion of in...

  12. Arsenic Species in the Ground Water

    EPA Science Inventory

    Abstract Arsenic concentrations in ground varies widely and regionally across the United States and exists as oxyanions having two oxidation states: As(+III) and As(+V). As(V) is effectively removed by most arsenic treatment processes whereas uncharged As(III) is poorly removed...

  13. Iron Amendments to Reduce Bioaccessible Arsenic

    EPA Science Inventory

    Former sugarcane lands on the Island of Hawaii have elevated soil arsenic (As) from historical use of arsenical pesticides. The bioaccessible fraction of total As (AsTOT), a measure of the potential for human As uptake by incidental ingestion of soil, is used in the a...

  14. Arsenic speciation in rice paddy soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arsenic can undergo several chemical and microbial transformations in soil, including oxidation/reduction, methylation/demethylation, and volatilization, which could impact arsenic bioavailability for plant uptake. An experiment was conducted in field plots at Stuttgart, AR to determine whether arse...

  15. In search of an arsenic MCL

    SciTech Connect

    Not Available

    1994-09-01

    Questions about arsenic continue to fan the flames of debate that surround the US Environmental Protection Agency's quest for a new, more appropriate maximum contaminant level (MCL) for arsenic. In making its decision, the USEPA is taking into account many factors, including occurrence, exposure and health effects, and treatment technologies. Recent studies in Taiwan on long-term human exposure show that arsenic in drinking water is associated with liver, lung, kidney, and bladder cancers as well as previously documented skin cancer. However, studies of several US communities served by water supplies containing high concentrations of arsenic failed to show excessive skin disorders, and the arsenic-induced risk of internal cancer in the US is uncertain. In response to the question of whether the current arsenic MCL (0.05 mg/L) protects health, these authors conclude that existing epidemiologic data are too limited to provide a definitive answer. Once USEPA has selected MCL options for arsenic, it will use occurrence data to develop a regulatory impact analysis; from this analysis the costs and benefits of compliance with the various MCLs can be estimated. In reviewing past surveys of arsenic occurrence and ongoing investigations of low-level occurrence, the latter are particularly important because USEPA is considering an MCL below 5 [mu]g/L.

  16. Arsenic Removal from Drinking Water - Web cast

    EPA Science Inventory

    Web cast presentation covered six topics: (1) Arsenic Chemistry, (2) Technology Selection/Arsenic Demonstration Program, (3) Case Study 1, (4) Caser Study 2, (5) Case Study 3, and (6) Media Regeneration Project. The presentation was considered a training session and consist of m...

  17. Process for upgrading arsenic-containing oils

    DOEpatents

    Sullivan, Richard F.

    1979-01-01

    A method is provided for avoiding feed-transfer-line plugging by a deposit comprising arsenic in hydroprocessing an oil containing an arsenic contaminant. In the method, a mixture of hydrogen gas and the oil is formed in situ in a bed of porous particulate contact material.

  18. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 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...

  19. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 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...

  20. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 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...