Inorganic Arsenic Compounds Research Articles

Massive Human Ingestion of Orpiment (Arsenic Trisulfide)

BackgroundBecause the toxicity of arsenic is well known, arsenic-containing compounds have frequently been ingested for suicidal purposes. We report a case of attempted suicide by massive ingestion of arsenic trisulfide, an arsenic mineral of low solubility, which resulted in minimal symptoms. Case ReportAn asymptomatic 57-year-old man presented to an Emergency Department 13h after his reported ingestion of approximately 84g of arsenic contained in a mineral specimen of orpiment (arsenic trisulfide) that had been crushed and mixed with an alcoholic beverage and food. His only symptom before presentation was nausea. Physical examination was unremarkable, and diagnostic tests included a normal electrolyte panel, a normal serum lactate, and a normal electrocardiogram. An abdominal radiograph revealed hyper-dense material scattered throughout the large intestine. As per the recommendations of the regional poison center, the patient was managed with whole bowel irrigation with a polyethylene glycol solution, maintenance intravenous hydration, and observation on a telemetry unit. Chelation was not performed. A spot urine specimen collected 12h after admission contained 1490μg of total arsenic per liter (background range<50μg per liter). The patient remained asymptomatic throughout his hospital course. Follow-up studies revealed a diminution in both intra-abdominal radiopacities and urine arsenic concentration. X-ray diffraction analysis of the specimen confirmed its identity as arsenic trisulfide. ConclusionsOur experience demonstrates that massive ingestion of a poorly soluble inorganic arsenic compound can be successfully managed with gastrointestinal decontamination alone without chelation, provided that the patient remains asymptomatic during close clinical monitoring.

Arsenic speciation in food chains from mid-Atlantic hydrothermal vents

Arsenic concentration and speciation were determined in benthic fauna collected from the Mid-Atlantic Ridge hydrothermal vents. The shrimp species, Rimicaris exoculata, the vent chimney-dwelling mussel, Bathymodiolus azoricus, Branchipolynoe seepensis, a commensal worm of B. azoricus, and the gastropod Peltospira smaragdina showed variations in As concentration and in stable isotope (δ13C and δ15N) signature between species, suggesting different sources of As uptake. Arsenic speciation showed arsenobetaine to be the dominant species in R. exoculata, whereas in B. azoricus and B. seepensis arsenosugars were most abundant, although arsenobetaine, dimethylarsinate, and inorganic arsenic were also observed, along with several unidentified species. Scrape samples from outside the vent chimneys, covered with microbial mat, which is a presumed food source for many vent organisms, contained high levels of total As, but organic species were not detectable. The formation of arsenosugars in pelagic environments is typically attributed to marine algae, and the pathway to arsenobetaine is still unknown. The occurrence of arsenosugars and arsenobetaine in these deep sea organisms, where primary production is chemolithoautotrophic and stable isotope analyses indicate food sources are of vent origin, suggests that organic arsenicals can occur in a food web without algae or other photosynthetic life.

Cyanobacteria produce arsenosugars

Environmental contextAlthough arsenic is known to accumulate in both marine and freshwater ecosystems, the pathways by which arsenic is accumulated and transferred in freshwater systems are reasonably unknown. This study revealed that freshwater cyanobacteria have the ability to produce arsenosugars from inorganic arsenic compounds. The findings suggest that not only algae, but cyanobacteria, play an important role in the arsenic cycle of aquatic ecosystems. AbstractMetabolic processes of incorporated arsenate in axenic cultures of the freshwater cyanobacteria Synechocystis sp. PCC 6803 and Nostoc (Anabaena) sp. PCC 7120 were examined. Analyses of arsenic compounds in cyanobacterial extracts using a high-performance liquid chromatography–inductively coupled plasma mass spectrometry system showed that both strains have an ability to biotransform arsenate into oxo-arsenosugar-glycerol within 20 min through (1) reduction of incorporated arsenate to arsenite and (2) methylation of produced arsenite to dimethylarsinic acid by methylarsonic acid as a possible intermediate product. In addition, Synechocystis sp. PCC 6803 cells are able to biosynthesise oxo-arsenosugar-phosphate from incorporated arsenate. These findings suggest that arsenosugar formation as well as arsenic methylation in cyanobacteria possibly play a significant role in the global arsenic cycle.

Speciated arsenic in air: Measurement methodology and risk assessment considerations

Accurate measurement of arsenic (As) in air is critical to providing a more robust understanding of arsenic exposures and associated human health risks. Although there is extensive information available on total arsenic in air, less is known on the relative contribution of each arsenic species. To address this data gap, the authors conducted an in-depth review of available information on speciated arsenic in air. The evaluation included the type of species measured and the relative abundance, as well as an analysis of the limitations of current analytical methods. Despite inherent differences in the procedures, most techniques effectively separated arsenic species in the air samples. Common analytical techniques such as inductively coupled plasma mass spectrometry (ICP-MS) and/or hydride generation (HG)- or quartz furnace (GF)-atomic absorption spectrometry (AAS) were used for arsenic measurement in the extracts, and provided some of the most sensitive detection limits. The current analysis demonstrated that, despite limited comparability among studies due to differences in seasonal factors, study duration, sample collection methods, and analytical methods, research conducted to date is adequate to show that arsenic in air is mainly in the inorganic form. Reported average concentrations of As(III) and As(V) ranged up to 7.4 and 10.4 ng/m⊃, respectively, with As(V) being more prevalent than As(III) in most studies. Concentrations of the organic methylated arsenic compounds are negligible (in the pg/m3 range). However, because of the variability in study methods and measurement methodology, the authors were unable to determine the variation in arsenic composition as a function of source or particulate matter (PM) fraction. In this work, the authors include the implications of arsenic speciation in air on potential exposure and risks. The authors conclude that it is important to synchronize sample collection, preparation, and analytical techniques in order to generate data more useful for arsenic inhalation risk assessment, and a more robust documentation of quality assurance/quality control (QA/QC) protocols is necessary to ensure accuracy, precision, representativeness, and comparability. Implications: The detailed review of the speciation techniques for arsenic in air samples presented in this study showed that (1) a variety of efficient methods (sampling, extraction, and analytical) developed across research studies were available for the determination of arsenic species in air; (2) arsenic species in the air were predominantly inorganic forms; and (3) the organic forms in air were largely below detection limits. Despite these general findings, more consistent methods must be developed to understand potential risks from arsenic in ambient air. Research needs to advance air arsenic risk assessment are identified.

MicroRNA‐181b and microRNA‐9 mediate arsenic‐induced angiogenesis via NRP1

Environmental exposure to inorganic arsenic compounds has been reported to have serious health effects on humans. Recent studies reported that arsenic targets endothelial cells lining blood vessels, and endothelial cell activation or dysfunction, may underlie the pathogenesis of arsenic-induced diseases and developmental toxicity. It has been reported that microRNAs (miRNAs) may act as an angiogenic switch by regulating related genes. The present study was designed to test the hypothesis that arsenite-regulated miRNAs play pivotal roles in arsenic-induced toxicity. Fertilized eggs were injected via the yolk sac with 100 nM sodium arsenite at Hamburger-Hamilton (HH) stages 6, 9, and 12, and harvested at HH stage 18. To identify the individual miRNAs and mRNAs that may regulate the genetic network, the expression profiles of chick embryos were analyzed by microarray analysis. Microarray analyses revealed that the expression of a set of miRNAs changed after arsenite administration, especially miRNA-9, 181b, 124, 10b, and 125b, which exhibited a massive decrease in expression. Integrative analyses of the microarray data revealed that several miRNAs, including miR-9 and miR-181b, might target several key genes involved in arsenic-induced developmental toxicity. A luciferase reporter assay confirmed neuropilin-1 (Nrp1) as a target of mir-9 and mir-181b. Data from the transwell migration assay and the tube-formation assay indicated that miR-9 and mir-181b inhibited the arsenic-induced EA.hy926 cell migration and tube formation by targeting NRP1. Our study demonstrates that the environmental toxin, sodium arsenite, induced angiogenesis by altering the expression of miRNAs and their cognate mRNA targets.

A multicenter phase II study of darinaparsin in relapsed or refractory Hodgkin's and non‐Hodgkin's lymphoma

Darinaparsin is a novel organic arsenic compound that is being developed to improve the efficacy and therapeutic index of arsenic as an antineoplastic agent. It has activity in preclinical models of hematological malignancies and we set out to test it in patients with refractory lymphoma. In this multicenter, Phase II trial, patients with relapsed or refractory Hodgkin (HL) and non-Hodgkin lymphoma (NHL) were treated with darinaparsin 300 mg/m 2 intravenously daily for five consecutive days every 28 days, for up to six cycles. The primary endpoint was the overall response rate. Twenty-nine heavily pretreated patients with lymphoma (22 with NHL and 7 with HL) were enrolled. There was one complete response (CR), one unconfirmed CR (CRu), three partial responses (PRs), and four with stable disease (SD), with an overall response rate of 17% (95% confidence interval (CI) 6–36%). Among the seven patients with peripheral T-cell lymphoma (PTCL), there was one CR, one CRu, and two with prolonged SD. The most common toxicities were fatigue, nausea, diarrhea, and anemia. Darinaparsin was safe and showed preliminary activity in this heavily pretreated population of relapsed/refractory lymphoma patients. Encouraging responses were seen in PTCL and further study in this subtype is planned. An estimated 74,030 people in the United States are diagnosed with HL or NHL every year with a global disease burden of approximately 350,000 new cases per year [1,2]. Major advances have been made over the last few decades in the treatment of these disorders in the form of combination chemotherapy, monoclonal antibody therapy, and stem cell transplantation [3–5], resulting in cure for a substantial proportion of cases. However, there remains a subgroup of patients who do not respond to standard therapy or relapse after an initial response. PTCL accounts for 7–10% of NHL cases and is a particularly unfavorable subtype [6]. Combination chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is the usual treatment approach for PTCL, but outcomes are generally poor even with more intensive regimens [7]. Darinaparsin (N-[S-(dimethylarsino)-N-L-gamma-glutamyl-L-cysteinyl]-glycine; S-dimethylarsino-glutathione, ZIO-101, Zinapar TM ) is a novel organic

ARSENIC METABOLITES IN HUMAN URINE AFTER INGESTION OF SASHIMI TSUNA FISH

Background and Aims: The consumption of seafood including tuna is increasing in the world. Seafood contains large amounts of various arsenic compounds but the risk from seafood ingestion is not clear. After the development of arsenic speciation analysis of seafood, we examined sashimi-grade tuna fish ingestion experiment using volunteers. Methods: Arsenic content of tuna was measured after bead-beating treatment and 50% methanol extraction. Four volunteers ingested 300 g of sashimi-grade tuna fish, after refraining from eating seafood for 5 days. Arsenic metabolites in urine were monitored over 5-day period after the ingestion. Speciation analysis of arsenic in tuna and urine was performed by high-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Results: Total arsenic (T-As) concentration of the tuna was 8.6 mgAs/kg. The compounds detected were arsenobetain (AsBe) and two unidentified arsenic compounds, but dimethylarsinic acid (DMA), monomethylarsonic acid, trimethylarsine oxide, arsenocholine, and inorganic arsenics (iAs) were not detected in 50% methanol extract. In 2.6 mg of arsenic ingested, 1.4 mg (54%) was AsBe and 0.4 mg (16%) of arsenic was insoluble arsenic. Approximately 40% of the ingested T-As was excreted in the urine during 5 days of the observation. The major urinary arsenics were AsBe and DMA, and the excreted total amounts were 948 ± 201 µg and 94 ± 38 µg, respectively. Approximately 70% of the ingested AsBe was excreted into the urine. Urinary AsBe excretion rate reached to 66.5 µg/h at 4 h after ingestion and that of DMA was 1.47 µg/h at 9 h. Conclusion: Tuna, one of the most popular seafood, contains not only AsBe but also at least two kinds of soluble organic arsenic compounds and 16% of insoluble arsenic. Since neither DMA nor iAs detected in tuna, urinary DMA may be produced metabolically from unidentified arsenics or insoluble arsenic compounds.

Antiproliferative and anti-invasive effects of inorganic and organic arsenic compounds on human and murine melanoma cells in vitro

For patients with advanced melanoma, no treatment options are available at present that provide either sufficient response rates or a significant prolongation of overall survival. The present study examines the effects of two inorganic and six organic arsenic compounds on cell proliferation and cell invasion of melanoma cells in vitro. The effects of arsenic compounds on proliferation of human melanoma A375 cells and murine melanoma B16F10 cells were examined by MTT assay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the effects of the compounds on cell invasion were examined by the Boyden chamber invasion assay. The amounts of active matrix metalloproteinase (MMP)-2 and pro-MMP-2 in the culture supernatant of A375 cells were determined by an MMP-2 activity assay system. Arsenate and arsenic trioxide (As(2) O(3) ) inhibited the proliferation of A375 and B16F10 cells significantly at concentration ranges of 0.1-20µg/ml (P<0.001), while the organic compounds arsenobetaine, arsenocholine, dimethylarsinic acid, methylarsonic acid, tetramethylarsonium and trimethylarsine oxide did not show any inhibitory effects even at 20µg/ml. Cell invasion of A375 and B16F10 cells through a layer of collagen IV was significantly inhibited by 0.1-20 µg/ml of arsenate or As(2) O(3) (P<0.05), while the organic compounds did not inhibit cell invasion. Arsenate or As(2) O(3) at 0.2-10µg/ml significantly inhibited the amount of active MMP-2 and pro-MMP-2 secreted into the A375 cell culture supernatant (P<0.05). Our findings show that the inorganic arsenic compounds arsenate and As(2) O(3) inhibit cell proliferation and prevent the invasive properties of melanoma cells, possibly by decreasing MMP-2 production from the cells.

Influence of aggregated particles on biodegradation activities for dimethylarsinic acid (DMA) in Lake Kahokugata

Aquatic arsenic cycles mainly depend on microbial activities that change the arsenic chemical forms and influence human health and organism activities. The microbial aggregates degrading organic matter are significantly related to the turnover between inorganic arsenic and organoarsenic compounds. We investigated the effects of microbial aggregates on organoarsenic mineralization in Lake Kahokugata using lake water samples spiked with dimethylarsinic acid (DMA). The lake water samples converted 1 μmol L −1 of DMA to inorganic arsenic for 28 d only under anaerobic and dark conditions in the presence of microbial activities. During the DMA mineralization process, organic aggregates >5.0 μm with bacterial colonization increased the densities. When the organic aggregates >5.0 μm were eliminated from the lake water samples using filters, the degradation activities were reduced. DMA in the lake water would be mineralized by the microbial aggregates under anaerobic and dark conditions. Moreover, DMA amendment enhanced the degradation activities in the lake water samples, which mineralized 50 μmol L −1 of DMA. The DMA-amended aggregates >5.0 μm completely degraded 1 μmol L −1 of DMA with a shorter incubation time of 7 d. The supplement of KNO 3 and NaHCO 3 to lake water samples also shortened the DMA-degradation period. Presumably, the bacterial aggregates involved in the chemical heterotrophic process would contribute to the DMA-biodegradation process in Lake Kahokugata, which is induced by the DMA amendment.

Development of a high-performance liquid chromatography method for the simultaneous quantification of four organoarsenic compounds in the feeds of swine and chicken

A high-performance liquid chromatography (HPLC) method with UV detection was developed for the simultaneous determination of arsanilic acid, roxarsone, nitarsone, and carbarsone in the feeds of swine and chicken. Feed samples were extracted with methanol/1% acetic acid (90:10, v/v) in an ultrasonic bath and the protein was precipitated with 2% Cu 2SO 4. The samples were further purified by solid phase extraction (SPE) on SAX cartridges. Separation was performed on a Zorbax SB-Aq C18 HPLC column using an isocratic procedure with methanol and 1% acetic acid (3:97, v/v) at a flow-rate of 0.7 mL min −1, and the UV detector was set at a wavelength of 260 nm. The recoveries of organoarsenic compounds spiked at levels of 2, 20 and 200 μg g −1 ranged from 81.2% to 91.3%; the inter-day relative standard deviation values were less than 7.0%. The limits of quantification for four organoarsenic compounds were 1.0–2.0 μg g −1. This simple and fast method could be applied to the determination of multi-residues of organic arsenic compounds in animal feeds.

Organic Arsenic in the Soil Environment: Speciation, Occurrence, Transformation, and Adsorption Behavior

An attempt is made to describe the fate and behavior of organic arsenic (As) compounds in the soil environment, based on an extensive literature researches. The objective of this review is to provide an overview on the state of knowledge to date about the occurrence and potential transformation of organic As, including methylation, degradation, and hydration, in soils and their uptake and accumulation in plants and animals. Accordingly, the biogeochemical cycle of organic As in the soil environment is proposed.

HPLC inorganic arsenic speciation analysis of samples containing high sulfuric acid and iron levels

To monitor the oxidation of arsenite to arsenate in oxidizing and bioleaching reactors, speciation analysis of the inorganic arsenic compounds is required. Existing arsenic speciation analysis techniques are based on the use of liquid chromatography columns coupled to detector equipment such as inductively coupled plasma optical emission spectrometry (ICP-OES). These techniques are fairly complex and expensive. Therefore, for analysis of arsenic speciation in our studies on thermophilic iron and arsenic oxidation, we developed a simple (and inexpensive) method based on anionic ion exclusion chromatography using sulfuric acid as mobile phase, followed by UV detection. The detection limit was 0.1 mg L−1 of arsenite (As3+) and 0.1 mg L−1 of arsenate (As5+). The method was validated with samples from an iron-oxidizing bioreactor containing 0.12 mol L−1 H2SO4, 1 g L−1 arsenic, and 3 g L−1 iron. Samples from arsenopyritic gold concentrates by partial bio-oxidation and leaching samples were analyzed, showing the usefulness of the method for arsenic contained in environmental compartments. We also describe the apparent effect of the arsenic valence state on ICP-OES detection for total arsenic.

Concentrations and speciation of arsenic in groundwater polluted by warfare agents

Groundwater polluted with phenylarsenicals from former warfare agent deposits and their metabolites was investigated with respect to the behavior of relevant arsenic species. Depth profiles at the estimated source and at about 1 km downgradient from the source zone were sampled. The source zone is characterized by high total arsenic concentrations up to 16 mg L −1 and is dominated by organic arsenic compounds. The concentrations in the downgradient region are much lower (up to 400 μg L −1) and show a high proportion of inorganic arsenic species. Iron precipitation seems to be an effective mechanism to prevent dispersion of inorganic arsenic as well as phenylarsonic acid. Reductive conditions were observed in the deeper zone with predominant occurrence of trivalent arsenic species. The inorganic species are in redox equilibrium, whereas the phenylarsenic compounds have variable proportions. Methylphenylarsinic acid was identified in groundwater in traces which indicates microbial degradation activity.

Abstract 3560: Evaluation of RNA-stress granules formation as an indicator of response to Darinaparsin in cancer cell lines

Abstract Darinaparsin (ZIO101) is a novel organic arsenic compound demonstrating clinical efficacy and a favorable safety profile in hematological cancers and solid tumors. Its mechanism of action includes disruption of mitochondrial functions and induction of apoptosis. We studied the ability of darinaparsin to induce RNA stress granules, a critical survival adaptation mechanism for cells under stress. Darinaparsin caused a stress granule response similar to sodium arsenite, but at lower concentrations. Treatment of cells with darinaparsin induced the formation of granules containing a number of proteins specifically associated with stress granules, including G3BP (the Ras-GAP SH3 domain binding protein), CCAR1 (Cell Cycle and Apoptosis Regulatory Protein-1), caprin-1 (Cytoplasmic Activation/Proliferation-associated protein1) and AKAP350A (AKAP9). However, darinaparsin led to development of a greater number of smaller granules compared to sodium arsenite-induced stress. We evaluated the effect of 0.5 mM arsenite or 0.05 mM darinaparsin on poorly differentiated uterine sarcoma (MES-SA) and the multiple drug resistant cell line MES-SA/Dx5 that was established from MES-SA cells. MES-SA/Dx5 cells express high levels of mdr-1 mRNA and P-glycoprotein. Both sodium arsenite and darinaparsin led to stress granule formation in both cell lines. However, MES-SA/Dx5 cells were extremely sensitive to darinaparsin treatment and exhibited a prominent loss of cell contact. The amount of cleaved PARP (a marker of apoptosis) determined at 48h and 72h after darinaparsin treatment was consistent with the immunofluorescence findings in that cleaved PARP was significantly elevated in MES-SA/Dx5 cells compared to MES-SA cells. This indicates enhanced cytotoxic effects of darinaparsin on this otherwise chemotherapeutic resistant cell line. We also evaluated the effect of darinaparsin and sodium arsenite on different leukemia cell lines including Jurkat (T-cell lymphoblastic leukemia derived), Oci and THP1 (acute myeloid leukemia derived). THP1 cells express wild type nucleophosmin (NPM), while Oci cells are heterozygous for its mutant form NPMc+. Interestingly, we found that Jurkat cells did not developed stress granules in response to darinaparsin treatment and this cell line showed accelerated toxicity compared with THP1 and Oci cells, which did form stress granules. These studies demonstrate that darinaparsin has a different spectrum of activity than sodium arsenite and can elicit differential toxicity on specific classes of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3560.

Detection of arsenic-containing hydrocarbons in canned cod liver tissue

Arsenic is a metalloid well known to be potentially toxic depending of its species. Lipid-soluble arsenicals (arsenolipids) are present in a wide range of biological samples in which they could play a role in the biosynthesis of organoarsenic compounds from inorganic arsenic compounds. Arsenolipids have recently attracted considerable interest. In order to gain deeper insights into the impact of arsenolipids new analytical approaches for reliable determination of this class of arsenic-containing hydrocarbons in various matrices are needed. High concentrations of arsenolipids were found in seafood which served as sample material in this study. We report the investigation of three arsenolipids found in canned cod liver from which they were extracted and purified by solid phase extraction (SPE) using a silica gel column and ethyl acetate/methanol as eluent. Analytical studies were conducted by means of gas chromatography coupled with ICP-MS, MIP-AES and EI-qMS and by TOF-MS. The results obtained by GC-ICP-MS and GC-MIP-AES showed the existence of numerous arsenic compounds in the SPE fractions collected. Three major peaks were found within a retention time window between 10 and 25 min. The presence of arsenic compounds in the fish tissue could be confirmed using GC-EI-qMS analysis. Corresponding information of the molecular weights of the major arsenic species were provided by TOF-MS which allows highly accurate mass determinations. The results showed the presence of the arsenic-containing hydrocarbons with the following molecular formulas: C 17H 37AsO (calculated for [M+H] + 333.2133; found 333.2136; Δ m = 0.90 ppm); C 19H 41AsO (calculated for [M+H] + 361.2446; found 361.2446; Δ m = 0.00 ppm); C 23H 37AsO (calculated for [M+H] + 405.2133; found 405.2145; Δ m = 2.96 ppm). Suggestions for the corresponding structures are discussed.

Nutrient and heavy metal content of edible seaweeds in New Zealand

The nutritional composition of four commercially available seaweeds, Macrocystis pyrifera, Undaria pinnatifida, Porphyra and Ecklonia radiata, was compared with six wild-harvested species, Ulva stenophylla, Porphyra, Ecklonia radiata, Durvillaea antarctica, Hormosira banksii and Undaria pinnatifida. In the wild-collected species, ash contents were high (19.8–26.6% dry weight). Carbohydrate content ranged from 45.4–66.9%, while protein varied from 6.1–32.7%. Some species had high levels of potassium (<71.2 g/kg) and calcium (<15.3 g/kg). Total arsenic concentrations were high in some species (<97 mg/kg), but the dominant forms were the organic arsenic compounds that are regarded as non-toxic. Inorganic arsenic was well below the New Zealand regulatory limit. The variation in proximate composition and mineral content was high among species collected at different times or locations and between different species. New Zealand's native and naturalized seaweeds are comparable to other edible seaweeds and would be a healthy addition to normal diets.

Molecular interaction between arsenic hydrate microcrystals and the cell-surface endopeptidase CD10 (neprilysin) – A possible link to the development of renal and cutaneous malignancies upon occupational exposure to arsenic compounds?

Arsenic poisoning has become a worldwide public health concern since arsenic is recognized as a human carcinogen although the detailed mechanisms of carcinogenesis related to arsenic exposure are not completely understood at present. In particular, the skin and the kidneys are prone to neoplastic transformation upon occupational exposure of the human body to inorganic arsenic compounds. The cell-surface endopeptidase CD10 is variably expressed in cutaneous and renal malignancies, and due to this expression profile, might theoretically be implicated in arsenic-induced skin and renal neoplasias. From the functional point of view, CD10 conveys important anti-tumorigenic effects brought about by the inactivation of neuropeptide growth factors implicated in cancer progression. Placing the focus on the structural composition of arsenic hydrate microcrystals encountered in the cellular microenvironment, the present hypothesis suggests so far neglected molecular interactions between arsenic microcrystals and membrane-bound CD10 to be implicated in arsenic-induced carcinogenesis.

Toxicity and Oxidative Stress Induced by Organic Arsenical Diphenylarsinic Acid and Inorganic Arsenicals and Their Effects on Spatial Learning Ability in Mice

In the present study, we investigated the oxidative stress induced by arsenical compounds in mice. Catalase (CAT) activity in the liver was decreased significantly when an organic arsenical compound, diphenylarsinic acid (DPAA), was administered to mice for 7 and 28 consecutive days. Reduced glutathione (GSH) was decreased significantly in the blood of the mice treated for 7 days with another organic arsenical, phenylmethyl arsonic acid (PMAA), and an inorganic arsenical, Na2HAsO4, as well as DPAA. GSH was also decreased significantly in the brain of the mice treated for 28 days with DPAA. Arsenic concentrations in the brain of the mice administered DPAA for 7 or 28 days were 1.6-3.0 times higher than those in the livers of these mice. The levels were about 3.0-14 times higher than those in the brains of mice administered inorganic arsenicals, suggesting that organic arsenicals tended to be more highly accumulated in the brain than inorganic arsenicals. The Morris water maze test supported these results, i.e., the latency time of the mice administered DPAA was significantly longer than that of the mice administered Na2HAsO4 or NaAsO2, as well as that of controls without arsenical. These results showed that DPAA decreased GSH in the blood, liver and brain, and that DPAA was more easily transferred to the brain. It was suggested that spatial learning ability was depressed by the accumulation of DPAA in the brain.

The influence of filter tube dimensions on the determination of arsenic with a transversely heated filter atomizer and atomic absorption spectrometry

The performance of a transversely heated filter atomizer (THFA) for the determination of inorganic arsenic (As) compounds was studied. The gain in sensitivity with the THFA was influenced by the length and internal diameter of the inserted filter in correspondence with theory. The accuracy of determination was evaluated by analysis of several Certified Reference Materials (CRMs), with good agreement between determined and certified values.

Rejoinder: Arsenic Exposure and Prevalence of Type 2 Diabetes

Rejoinder: Arsenic Exposure and Prevalence of Type 2 Diabetes