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Dimethylarsinic Acid (dimethylarsinic + acid)
Selected AbstractsPromotion of Skin Carcinogenesis by Dimethylarsinic Acid in Keratin (K6)/ODC Transgenic MiceCANCER SCIENCE, Issue 6 2000Takashi Morikawa Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals in mammals, and arsenic exposure is associated with tumor development in a wide variety of human tissues, particularly the skin. Transgenic mice with ornithine decarboxylase (ODC) targeted to hair follicle keratinocytes are much more sensitive than littermate controls to carcinogens. In this study we investigated the promoting effect of DMA on skin carcinogenesis in such K6/ODC transgenic mice. The back skin of female C57BL/6J K6/ODC transgenic mice, 10 to 14 weeks old, was initiated with topical application of 7,12-dimethylbenz[,]anthracene (DMBA) at a dose of 50 ,g or acetone alone on day 1 of the experiment, followed by treatment with 3.6 mg of DMA, 5 ,g of 12-O-tetradecanoylphorbol-13-acetate (TPA) or neutral vehicle (control) twice a week for 18 weeks. Mice were killed 1 week after the end of the treatment. Induction of skin tumors was significantly accelerated in the DMA-treated group, as well as in the TPA-treated group, indicating that DMA has a promoting effect on skin tumorigenesis in K6/ODC transgenic mice. [source] Uptake and transport of roxarsone and its metabolites in water spinach as affected by phosphate supplyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2010Lixian Yao Abstract Roxarsone (ROX) is widely used as a feed additive in intensive animal production. While an animal is fed with ROX, the As compounds in the manure primarily occur as ROX and its metabolites, including arsenate (As[V]), arsenite (As[III]), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Animal manure is commonly land applied with phosphorous fertilizers in China. A pot experiment was conducted to investigate the phytoavailability of ROX, As(V), As(III), MMA, and DMA in water spinach (Ipomoea aquatica), with the soil amended with 0, 0.25, 0.50, 1.0, and 2.0,g PO4/kg, respectively, plus 2% (w/w manure/soil) chicken manure (CM) bearing ROX and its metabolites. The results indicate that this species of water spinach cannot accumulate ROX and MMA at detectable levels, but As(V), As(III), and DMA were present in all plant samples. Increased phosphorous decreased the shoot As(V) and As(III) in water spinach but did not affect the root As(V). The shoot DMA and root As(III) and DMA were decreased/increased and then increased/decreased by elevated phosphorous. The total phosphorous content (P) in plant tissue did not correlate with the total As or the three As species in tissues. Arsenate, As(III), and DMA were more easily accumulated in the roots, and phosphate considerably inhibited their upward transport. Dimethylarsinic acid had higher transport efficiency than As(V) and As(III), but As(III) was dominant in tissues. Conclusively, phosphate had multiple effects on the accumulation and transport of ROX metabolites, which depended on their levels. However, proper utilization of phosphate fertilizer can decrease the accumulation of ROX metabolites in water spinach when treated with CM containing ROX and its metabolites. Environ. Toxicol. Chem. 2010;29:947,951. © 2009 SETAC [source] Dose-dependent uptake, elimination, and toxicity of monosodium methanearsonate in adult zebra finches (Taeniopygia guttata)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2008Courtney A. Albert Abstract Monosodium methanearsonate (MSMA), an arsenic-based pesticide, has been used for the past 10 years in attempts to suppress mountain pine beetle (Dendroctonus ponderosae) outbreaks in British Columbia, Canada. Previous studies have shown that cavity nesting forest birds such as woodpeckers forage and breed in MSMA treated pine stands. Here we examined the effects of MSMA in the laboratory using the zebra finch (Taeniopygia guttata), with the objective to examine tissue distribution and sublethal toxic effects in a model avian species. Zebra finches were exposed to this pesticide at doses similar to those found in bark beetle samples from MSMA stands of trees treated in the southern interior of British Columbia (8, 24, and 72 ,g/g/d and a control group). Results showed high excretion (>90%) of arsenic in all dose groups, as well as dose-dependent trends in accumulation of arsenic in the blood (p < 0.001) and specific tissues. Monomethylarsonic acid, MMA (V), was the predominant form of arsenic in the blood plasma. Dimethylarsinic acid was the major form of arsenic found in the liver (83%) and kidney (61%) tissues. The brain tissue contained primarily the MMA (V) form (57%). Significant weight loss occurred in the two highest dose groups (p < 0.05). Birds in the highest dose group lost up to 15% of initial body mass. [source] Nitrogen purity influences the occurrence of As+ ions in high-performance liquid chromatography/electrospray ionization mass spectrometric analysis of four common arsenosugarsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2003Doris Kuehnelt High-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC/ESI-MS) can provide both elemental and molecular information and, therefore, is a very useful tool for the identification of arsenic compounds. When a method for the identification of four arsenosugars was employed in our laboratory with an HPLC/ESI-MS system equipped with a Whatman model 75-72 nitrogen generator, a signal at m/z 75 (As+) could not be observed. When the HPLC/ESI-MS system was operated with nitrogen 5.0 (nitrogen of a purity of at least 99.999%) all four arsenosugars gave a signal at m/z 75. Because of this observation the influence of the quality of the nitrogen drying gas on the fragmentation of the four arsenosugars was systematically investigated. Standard solutions containing the four arsenosugars (0.5 ng As each) were separated on an anion-exchange column and detected with ESI-MS in the positive ion mode by monitoring the signals for [M+H]+, m/z 237, 91, and 75. Nitrogen with defined oxygen concentrations was used as drying gas. The purity of the nitrogen ranged from 99 to 99.999% (10,400 to 10 ppm oxygen impurity). The nitrogen with 99% purity gave no signal at m/z 75, but signals were obtained at m/z 91, 237, and for [M+H]+. When higher purity nitrogen (99.9%) was used, a signal was obtained at m/z 75, which accounted for 0.8,1.1% (depending on the kind of arsenosugar) of the sum of the signals for m/z 75, 91, 237 and [M+H]+. As the level of oxygen in the nitrogen decreased, the m/z 75 signal increased to 2.0,3.1%. This was accompanied by a concomitant decrease in the m/z 91 signal from 5.2,6.6% to 0.7,1.5%, whereas the signals for [M+H]+ and m/z 237 were essentially unchanged. Signals at m/z 75 with intensities comparable with those observed for the 99.9% pure nitrogen were also obtained for all the arsenosugars when the HPLC/ESI-MS system was operated with a Domnick Hunter Nitrox UHPLCMS18 nitrogen generator. Dimethylarsinic acid, arsenobetaine, trimethylarsine oxide, arsenocholine and the tetramethylarsonium cation also gave no signal at m/z 75 when they were analyzed with the Whatman model 75-72 nitrogen generator, but clear signals at m/z 75 were observed with the Domnick Hunter Nitrox UHPLCMS18 nitrogen generator. A nitrogen quality of at least 99.9% is required to obtain elemental information (m/z 75) when arsenic compounds are investigated by HPLC/ESI-MS. Molecular and elemental information from one chromatographic run is a valuable tool for the characterization of unknown arsenic compounds. Copyright © 2003 John Wiley & Sons, Ltd. [source] Enteric bacteria may play a role in mammalian arsenic metabolismAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 6 2001Koichi Kuroda Abstract The cecal content of rats administered dimethylarsinic acid for 6 months via drinking water was cultured in GAM medium with 10,mg l,1 of dimethylarsinic acid. Arsenic compounds in the culture were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC,ICP-MS). Dimethylarsinic acid was metabolized. Two bacterial Escherichia coli strains, A3-4 and A3-6, were isolated from the culture. These strains metabolized dimethylarsinic acid and yielded two unidentified arsenic compounds, M-2 and M-3. A3-6 methylated dimethylarsinic acid to trimethylarsine oxide. Both strains metabolized trimethylarsine oxide and yielded an unidentified arsenic compound, M-1. These unknown arsenic compounds were the same compounds as detected in the urine and the feces of rats administered dimethylarsinic acid. The strains reduced arsenate to arsenite efficiently. Cysteine was required for metabolism of dimethylarsinic acid by these bacteria, but glutathione was not required. These results strongly suggested that the intestinal bacteria have a different arsenic metabolism from that in mammals and that they may play a possible role in mammalian arsenic metabolism. Copyright © 2001 John Wiley & Sons, Ltd. [source] Biologically mediated mobilization of arsenic from granular ferric hydroxide in anaerobic columns fed landfill leachateBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2008Irail Cortinas Abstract To gain insight on the fate of arsenic (As) from drinking water treatment residuals in landfills, the mobilization of arsenate adsorbed onto granular ferric hydroxide (GFH) was studied in continuous anaerobic columns fed with a synthetic landfill leachate. The release of As was compared in biologically active and abiotic columns. More than 150 days of incubation were required before noteworthy As release occurred. After 400 days of operation, 19% of the As was mobilized as identified species in the biologically active column, which was 25.5-fold greater than that of the abiotic column. Fine colloids accounted for up to 81% of the As released. Arsenite was the predominant species identified in filtered (0.45 µm) effluent samples. Dimethylarsinic acid and monomethylarsonic acid were also observed as metabolites. During column operation, approximately 30% of the iron (hydr)oxide mass was lost and most of the mass loss was attributed to changes in iron mineralogy that could be demonstrated in a batch bioassay. The results indicate that As-laden GFH residuals from drinking water treatment are subject to mobilization in municipal landfills and that biologically mediated changes in the iron mineralogy may play an important role in the mobilization mechanism. Biotechnol. Bioeng. 2008;101: 1205,1213. © 2008 Wiley Periodicals, Inc. [source] Promotion of Skin Carcinogenesis by Dimethylarsinic Acid in Keratin (K6)/ODC Transgenic MiceCANCER SCIENCE, Issue 6 2000Takashi Morikawa Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals in mammals, and arsenic exposure is associated with tumor development in a wide variety of human tissues, particularly the skin. Transgenic mice with ornithine decarboxylase (ODC) targeted to hair follicle keratinocytes are much more sensitive than littermate controls to carcinogens. In this study we investigated the promoting effect of DMA on skin carcinogenesis in such K6/ODC transgenic mice. The back skin of female C57BL/6J K6/ODC transgenic mice, 10 to 14 weeks old, was initiated with topical application of 7,12-dimethylbenz[,]anthracene (DMBA) at a dose of 50 ,g or acetone alone on day 1 of the experiment, followed by treatment with 3.6 mg of DMA, 5 ,g of 12-O-tetradecanoylphorbol-13-acetate (TPA) or neutral vehicle (control) twice a week for 18 weeks. Mice were killed 1 week after the end of the treatment. Induction of skin tumors was significantly accelerated in the DMA-treated group, as well as in the TPA-treated group, indicating that DMA has a promoting effect on skin tumorigenesis in K6/ODC transgenic mice. [source] Speciation of arsenic compounds in fish and oyster tissues by capillary electrophoresis-inductively coupled plasma-mass spectrometryELECTROPHORESIS, Issue 7-8 2005Ching-Fen Yeh Abstract A capillary electrophoresis-inductively coupled plasma-mass spectrometric (CE-ICP-MS) method for the speciation of six arsenic compounds, namely arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid, dimethylarsinic acid, arsenobetaine and arsenocholine is described. The separation has been achieved on a 70,cm length×75,µm,ID fused-silica capillary. The electrophoretic buffer used was 15,mM Tris (pH,9.0) containing 15,mM sodium dodecyl sulfate (SDS), while the applied voltage was set at +22,kV. The arsenic species in biological tissues were extracted into 80%,v/v methanol-water mixture, put in a closed centrifuge tube and kept in a water bath, using microwaves at 80°C for 3,min. The extraction efficiencies of individual arsenic species added to the sample at 0.5,µg As/g level were between 96% and 107%, except for As(III), for which it was 89% and 77% for oyster and fish samples, respectively. The detection limits of the species studied were in the range 0.3,0.5,ng As/mL. The procedure has been applied for the speciation analysis of two reference materials, namely dogfish muscle tissue (NRCC DORM-2) and oyster tissue (NIST SRM 1566a), and two real-world samples. [source] Trace determination of arsenic species by capillary electrophoresis with direct UV detection using sensitivity enhancement by counter- or co-electroosmotic flow stacking and a high-sensitivity cellELECTROPHORESIS, Issue 12-13 2003Baoguo Sun Abstract Stacking techniques used independently and also with a high-sensitivity cell (HSC) were employed to optimise sensitivity and detection limits in the direct photometric detection of the following eight arsenic species by capillary zone electrophoresis (CZE): arsenite, arsenate, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), 4-hydroxy-3-nitrophenylarsonic acid (Roxarsone), p -aminophenylarsonic acid (p -ASA), 4-nitrophenylarsonic acid (4-NPAA), and phenylarsonic acid (PAA) (target analytes). The stacking mechanisms, optimised stacking and separation conditions, and concentration sensitivity enhancement factors were discussed and compared for (i) normal stacking mode (NSM, sometimes also referred to as field-amplified stacking) in an uncoated fused-silica capillary in the counter-electroosmotic flow (EOF) mode, (ii) large-volume sample stacking (LVSS) with polarity switching, and (iii) the less often applied stacking method of co-EOF NSM stacking with EOF reversal using a poly(diallydimethylammonium chloride) (PDDAC)-coated capillary. The optimal injection volumes were 7.4, 60 and 17.2% of the total capillary volume, for the above three methods, respectively. LVSS with polarity switching gave the lowest limit of detection (LOD). The use of the HSC further reduced the LOD of each target analytes by a factor of 5,8 times. By combining LVSS and HSC, LODs of the target analytes could be reduced by a factor of 218,311, to 5.61, 9.15, 11.1, and 17.1 ,g/L for As(III), DMA, MMA, and As(V), respectively. The method was demonstrated to be applicable to the determination of the target analytes in tap water and lake water, with recoveries in the range of 89.4,103.3%. [source] Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009Amy Wang Abstract Arsenic is a human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the skin and urinary bladder. Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include oxidative stress induction and inhibition of DNA damage repair. We investigated the effects of arsenic in drinking water on DNA damage repair in urinary bladder transitional cells and on micronucleus formation in bone marrow. F344 rats were given 100 ppm arsenate [As(V)] or dimethylarsinic acid [DMA(V)] in drinking water for 1 week. The in vivo repair of cyclophosphamide (CP)-induced DNA damage resulting from a single oral gavage of CP, and the in vitro repair of hydrogen peroxide (H2O2)- or formaldehyde-induced DNA damage, resulting from adding H2O2 or formaldehyde into cell medium, were measured by the Comet assay. DMA(V) effects were not observed on either CP-induced DNA damage induction or on DNA repair. Neither DMA(V) nor As(V) increased the H2O2 - or formaldehyde-induced DNA damage, and neither inhibited the repair of H2O2 -induced DNA damage. Neither DMA(V) nor As(V) increased the micronucleus frequency, nor did they elevate micronucleus frequency resulting from CP treatment above the level observed by the treatment with CP alone. These results suggest that arsenic carcinogenesis/cocarcinogenesis in the urinary bladder may not be via DNA damage repair inhibition. To our knowledge this is the first report of arsenic effects on DNA damage repair in the urinary bladder. Environ. Mol. Mutagen. 2009. Published 2009 by Wiley-Liss, Inc. [source] Uptake and transport of roxarsone and its metabolites in water spinach as affected by phosphate supplyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2010Lixian Yao Abstract Roxarsone (ROX) is widely used as a feed additive in intensive animal production. While an animal is fed with ROX, the As compounds in the manure primarily occur as ROX and its metabolites, including arsenate (As[V]), arsenite (As[III]), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Animal manure is commonly land applied with phosphorous fertilizers in China. A pot experiment was conducted to investigate the phytoavailability of ROX, As(V), As(III), MMA, and DMA in water spinach (Ipomoea aquatica), with the soil amended with 0, 0.25, 0.50, 1.0, and 2.0,g PO4/kg, respectively, plus 2% (w/w manure/soil) chicken manure (CM) bearing ROX and its metabolites. The results indicate that this species of water spinach cannot accumulate ROX and MMA at detectable levels, but As(V), As(III), and DMA were present in all plant samples. Increased phosphorous decreased the shoot As(V) and As(III) in water spinach but did not affect the root As(V). The shoot DMA and root As(III) and DMA were decreased/increased and then increased/decreased by elevated phosphorous. The total phosphorous content (P) in plant tissue did not correlate with the total As or the three As species in tissues. Arsenate, As(III), and DMA were more easily accumulated in the roots, and phosphate considerably inhibited their upward transport. Dimethylarsinic acid had higher transport efficiency than As(V) and As(III), but As(III) was dominant in tissues. Conclusively, phosphate had multiple effects on the accumulation and transport of ROX metabolites, which depended on their levels. However, proper utilization of phosphate fertilizer can decrease the accumulation of ROX metabolites in water spinach when treated with CM containing ROX and its metabolites. Environ. Toxicol. Chem. 2010;29:947,951. © 2009 SETAC [source] Bioaccumulation and biotransformation of arsenic in the Mediterranean polychaete Sabella spallanzanii experimental observationsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2007Alessandra Notti Abstract The Mediterranean fan worm Sabella spallanzanii is characterized by elevated basal levels of arsenic in branchial crowns (>1,000 ,g/g) and an unusual prevalence of dimethylarsinic acid (DMA), a relatively toxic compound with a possible antipredatory role. The aim of this work was to obtain further insights on the capability of this polychaete to accumulate arsenic from different compounds and to operate biotransformation reactions. Laboratory exposures to arsenate (AsV), dimethylarsinic acid (DMA), trimethylarsine (TMA), and arsenobetaine (AsB) revealed significant differences among tissues and kind of experiments. The highest increases of arsenic content were observed in branchial crowns of organisms treated with arsenate, which can enter the cell through the phosphate carrier system; lower variations were measured with DMA and TMA, while not-significant changes of total As occurred after treatments with AsB. In body tissues, exposure to AsV, DMA, and TMA confirmed a progressively lower accumulation of total arsenic, while a marked increase was caused by AsB. Obtained results suggested that accumulated arsenic could be chemically transformed, thus explaining the elevated basal levels of DMA typical of S. spallanzanii; during all the experiments, DMA was the most accumulated molecule, suggesting that this species possesses the enzymatic pathways for methylation and demethylation reactions of inorganic and trimethylated arsenicals. Only arsenobetaine was not converted into DMA, which would confirm a microbial pathway for degradation for this molecule, particularly important in body tissues of S. spallanzanii for the presence of bacteria associated to digestive tracts. Overall, the present study suggests future investigations on the biological role of arsenic and DMA in S. spallanzanii as a potential adaptive mechanism against predation in more vulnerable tissues. [source] A simple and fast detection technique for arsenic speciation based on high-efficiency photooxidation and gas-phase chemiluminescence detectionLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 5 2009Junhai Xue Abstract High-efficiency photooxidation (HEPO) and gas phase chemiluminescence detection (CL) combined with high-performance liquid chromatography (HPLC) and hydride generation were developed for speciation of As(III), As(V), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). After chromatography separation, the arsenic species were passed through HEPO which performed efficient photooxidation and converted MMA and DMA to As(V) in several seconds. Then the reaction of ozone and arsine upon hydride generation produced a CL signal as the analytical parameter. The total analytical process was completed within 10 min. The effects of operational parameters such as the concentrations of hydrochloric acid and NaBH4 solution, carrier gas flow and air gas flow for ozone generation were investigated. Detection limits were 3.7, 10.3, 10.2 and 10.0 µg/L for As(III), As(V), MMA and DMA, respectively. The recoveries of the four arsenic species in human urine sample ranged from 87 to 94%. Copyright © 2009 John Wiley & Sons, Ltd. [source] Distribution and fate of biologically formed organoarsenicals in coastal marine sedimentAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 8 2005Mio Takeuchi Abstract Marine organisms, including phyto- and zoo-plankton, macroalgae, and animals, concentrate arsenic in various organic forms. However, the distribution and fate of these organoarsenicals in marine environments remains unclear. In this study, the distribution of organoarsenicals in coastal marine sediment in Otsuchi Bay, Japan, has been determined. Methylarsonic acid, dimethylarsinic acid, trimethylarsine oxide, arsenobetaine, arsenocholine and other unidentified arsenic species were detected in marine sediment by high-performance liquid chromatography,inductively coupled plasma mass spectrometry analysis of methanol,water extracts. Arsenobetaine was the dominant organoarsenical at four of the seven stations where tests were carried out, and unidentified species or dimethylarsinic acid dominated at the other stations. Total organoarsenicals (as arsenic) in the surface sediment amounted to 10.6,47.5 µg kg,1 dry sediment. Core analysis revealed that concentrations of organoarsenicals decreased with depth, and they are considered to be degraded within 60 years of deposition. These results show that organoarsenicals formed by marine organisms are delivered to the sediment and can be degraded within several decades. Copyright © 2005 John Wiley & Sons, Ltd. [source] Accumulation of arsenic by Traustochytrium sp.APPLIED ORGANOMETALLIC CHEMISTRY, Issue 8 2002CHN-1 from Seto Inland Sea Abstract The accumulation of arsenic by Traustochytrium sp. CHN-1 (Labyrinthulids) was examined by using a medium [2% (w/v) glucose, 0.1% (w/v) yeast extract, 0.1% (w/v) peptone in a half salt concentration of sea water] containing arsenic as As(V), As(III). Traustochytrium sp. CHN-1 was grown in 1/2 sea water medium [2% (w/v) glucose, 0.1% (w/v) yeast extract, 0.1% (w/v) peptone] containing an arsenate (As(V)) at up to 1000,mg dm,3 and arsenite (As(III)) at up to 50,mg dm3. The cells died even at [As(III)]-100,mg dm,3. These results suggested that the order of growth inhibition of Traustochytrium sp. CHN-1 by arsenic was As(III),>,As(V). The biomass of Traustochytrium sp. CHN-1 decreased with an increase of the surrounding arsenic concentration. On the other hand, the arsenic concentration in cells increased with an increase of the surrounding arsenic concentration. Arsenic compounds were extracted with methanol/water (1:1) from a freeze-dried sample of Traustochytrium sp. CHN-1. The extracts were analyzed by high-performance liquid chromatography, with an inductively coupled plasma mass spectrometer serving as an arsenic-specific detector. Arsenite, arsenate, monomethylarsonic acid (MMAA), dimethylarsinic acid (DMAA) and arsenosugar were identified in Traustochytrium sp. CHN-1. The order of arsenic species in Traustochytrium sp. CHN-1 was As(V),>,DMAA,>,As(III),>,MMAA,>,arsenosugar at [As]-10,mg dm,3 in the medium. Detoxification of arsenic by cells was probably achieved by methylation. Copyright © 2002 John Wiley & Sons, Ltd. [source] Cysteine enhances clastogenic activity of dimethylarsinic acidAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 7 2002Mari Kitamura Abstract The effects of cysteine on dimethylarsinic acid (DMA)-induced cytotoxicity and chromosomal aberration were studied using Chinese hamster V79 cells. The IC 50 of DMA, i.e. the concentration resulting in a 50% decrease in cell population of viable cells, was 130,µg,ml,1 (0.94 mM), whereas that in the presence of 50,µg,ml,1 (0.28 mM) cysteine was 20,µg,ml,1 (0.14 mM). The mitotic index with co-administration of 50,µg,ml,1 (0.36 mM) DMA and 50,µg,ml,1 cysteine was 1.4 times that with 50,µg,ml,1 DMA alone. Whereas 82% of cells divided twice with 25,µg,ml,1 (0.18 mM) DMA alone, most cells divided only once with co-administration of 25,µg,ml,1 DMA and 50,µg,ml,1 cysteine. These results indicated that the increase in mitotic index by cysteine was due to enhancement of mitotic arrest by DMA. With co-administration of 25,µg,ml,1 DMA and 50,µg,ml,1 cysteine, tetraploidy was 14.3% higher and fivefold by that with 25,µg,ml,1 DMA only. Cysteine at 50,µg,ml,1 enhanced induction of chromosomal aberrant cells by DMA. 100,µg,ml,1 (0.72 mM) DMA induced 91% chromosomal aberrant cells in the presence of cysteine, and 12% in the absence of cysteine. Chromatid breaks and chromatid gaps were the most frequent types of aberration induced by co-administration of DMA and cysteine or DMA alone. Co-administration of DMA and cysteine produced many attenuated chromosomal figures. The attenuated chromosomal figures always had several chromatid gaps and chromatid breaks. Our findings may provide clues to arsenic carcinogenesis in humans. Copyright © 2002 John Wiley & Sons, Ltd. [source] Organoarsenic compounds in plants and soil on top of an ore veinAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 5 2002Anita Geiszinger Abstract Plants and soil collected above an ore vein in Gasen (Austria) were investigated for total arsenic concentrations by inductively coupled plasma mass spectrometry (ICP-MS). Total arsenic concentrations in all samples were higher than those usually found at non-contaminated sites. The arsenic concentration in the soil ranged from ,700 to ,4000,mg kg,1 dry mass. Arsenic concentrations in plant samples ranged from ,0.5 to 6,mg kg,1 dry mass and varied with plant species and plant part. Examination of plant and soil extracts by high-performance liquid chromatography,ICP-MS revealed that only small amounts of arsenic (<1%) could be extracted from the soil and the main part of the extractable arsenic from soil was inorganic arsenic, dominated by arsenate. Trimethylarsine oxide and arsenobetaine were also detected as minor compounds in soil. The extracts of the plants (Trifolium pratense, Dactylis glomerata, and Plantago lanceolata) contained arsenate, arsenite, methylarsonic acid, dimethylarsinic acid, trimethylarsine oxide, the tetramethylarsonium ion, arsenobetaine, and arsenocholine (2.5,12% extraction efficiency). The arsenic compounds and their concentrations differed with plant species. The extracts of D. glomerata and P. lanceolata contained mainly inorganic arsenic compounds typical of most other plants. T. pratense, on the other hand, contained mainly organic arsenicals and the major compound was methylarsonic acid. Copyright © 2002 John Wiley & Sons, Ltd. [source] Comparison of three methods for the extraction of arsenic compounds from the NRCC standard reference material DORM-2 and the brown alga Hijiki fuziformeAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 6 2001Doris Kuehnelt Abstract The NRCC standard reference material DORM-2 and the marine brown alga Hijiki fuziforme were extracted with water, methanol/water (9,+,1), and 1.5 M orthophosphoric acid. The extracts from DORM-2 were analyzed by HPLC,ICP-MS for arsenobetaine, arsenocholine, trimethylarsine oxide, and the tetramethylarsonium cation and the extracts from H. fuziforme for arsenous acid, arsenic acid, dimethylarsinic acid, methylarsonic acid, and four arsenoriboses. Almost no differences between the three extractants were observed when DORM-2 was investigated. Only arsenobetaine was slightly better extracted with 1.5 M orthophosphoric acid or methanol/water (9,+,1) than with water. The sum of all extractable compounds (arsenobetaine, the tetramethylarsonium cation, and a formerly unknown compound recently identified as the trimethyl(2-carboxyethyl)arsonium ion) accounted for 94% of the total arsenic when 1.5 M orthophosphoric acid was used, for 92% when methanol/water (9,+,1) was used, and for 87% when water was used. Significant differences in the extraction yields obtained for the alga were observed for arsenic acid and one of the arsenoriboses (,glycerol-ribose'). Orthophosphoric acid removed twice as much of this ribose from the algal material than water and three times more than methanol/water (9,+,1). Arsenic acid was 1.2 times better extracted with orthophosphoric acid than with water and ten times better than with methanol/water (9,+,1). Almost no differences in the extraction yields were found for dimethylarsinic acid and the other three riboses. Orthophosphoric acid extracted 76%, water 65%, and methanol/water 33% of the total arsenic from H. fuziforme. Copyright © 2001 John Wiley & Sons, Ltd. [source] Metabolism of dimethylarsinic acid in rats: production of unidentified metabolites in vivoAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 6 2001Kaoru Yoshida Abstract Our previous study revealed that two unidentified metabolites, M-1 and M-2, were excreted in urine after long-term oral administration of dimethylarsinic acid (DMA), the main metabolite of inorganic arsenic. In the present study, we attempted to clarify the mechanism of production of these unknown metabolites. Male F344/DuCrj rats were administered a single dose of DMA (50,mg kg,1) orally or intraperitoneally with or without pretreatment with L -buthionine-SR-sulfoximine (BSO), which inhibits glutathione (GSH) synthesis. Urine was collected by forced urination at various time points after administration of DMA. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC,ICP-MS). The unidentified metabolites M-1 and M-2 were excreted later than elimination of DMA and trimethylarsine oxide (TMAO). GSH depletion decreased in TMAO elimination, suggesting that GSH plays important roles in the methylation of DMA to TMAO in rats. There was no difference in the amount of production of either M-1 or M-2 between BSO-pretreated rats and controls, suggesting that M-1 and M-2 cannot be formed during methylation in the liver. The amounts of elimination of M-1 and M-2 were less after intraperitoneal administration than after oral administration. Male F344/DuCrj rats were given 100,mg As l,1 DMA via drinking water for 20 weeks. Urine and feces were collected forcibly and were analyzed by IC,ICP-MS. A new unidentified metabolite, M-3, was detected only in feces as a metabolite of DMA after 20 weeks exposure to DMA, although M-1 and M-2 were found in both urine and feces. The unidentified metabolites M-1, M-2, and M-3 were excreted mainly as fecal metabolites along with unmetabolized DMA. This finding also suggests that M-1, M-2, and M-3 might be produced in the intestinal tract. Copyright © 2001 John Wiley & Sons, Ltd. [source] Enteric bacteria may play a role in mammalian arsenic metabolismAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 6 2001Koichi Kuroda Abstract The cecal content of rats administered dimethylarsinic acid for 6 months via drinking water was cultured in GAM medium with 10,mg l,1 of dimethylarsinic acid. Arsenic compounds in the culture were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC,ICP-MS). Dimethylarsinic acid was metabolized. Two bacterial Escherichia coli strains, A3-4 and A3-6, were isolated from the culture. These strains metabolized dimethylarsinic acid and yielded two unidentified arsenic compounds, M-2 and M-3. A3-6 methylated dimethylarsinic acid to trimethylarsine oxide. Both strains metabolized trimethylarsine oxide and yielded an unidentified arsenic compound, M-1. These unknown arsenic compounds were the same compounds as detected in the urine and the feces of rats administered dimethylarsinic acid. The strains reduced arsenate to arsenite efficiently. Cysteine was required for metabolism of dimethylarsinic acid by these bacteria, but glutathione was not required. These results strongly suggested that the intestinal bacteria have a different arsenic metabolism from that in mammals and that they may play a possible role in mammalian arsenic metabolism. Copyright © 2001 John Wiley & Sons, Ltd. [source] Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in a rat liver cell line (TRL 1215)BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2006T Sakurai Background and purpose: Although inorganic arsenite (AsIII) is toxic in humans, it has recently emerged as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). In humans and most animals, AsIII is enzymatically methylated in the liver to weakly toxic dimethylarsinic acid (DMAsV) that is a major pentavalent methylarsenic metabolite. Recent reports have indicated that trivalent methylarsenicals are produced through methylation of AsIII and participate in arsenic poisoning. Trivalent methylarsenicals may be generated as arsenical,glutathione conjugates, such as dimethylarsinous glutathione (DMAsIIIG), during the methylation process. However, less information is available on the cytotoxicity of DMAsIIIG. Experimental approach: We synthesized and purified DMAsIIIG using high performance TLC (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215 cells). Key results: DMAsIIIG was highly cytotoxic in TRL 1215 cells with a LC50 of 160 nM. We also found that DMAsIIIG molecule itself was not transported efficiently into the cells and was not cytotoxic; however it readily became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and glutathione (GSH). The addition of GSH in micromolar physiological concentrations prevented the breakdown of DMAsIIIG, and the DMAsIIIG-induced cytotoxicity. Physiological concentrations of normal human serum (HS), human serum albumin (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and cellular arsenic uptake induced by exposure to DMAsIIIG. Conclusions and implications: These findings suggest that the significant cytotoxicity induced by DMAsIIIG may not be seen in healthy humans, even if DMAsIIIG is formed in the body from AsIII. British Journal of Pharmacology (2006) 149, 888,897. doi:10.1038/sj.bjp.0706899 [source] | ||||||||||||||||