@article {330, title = {Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin}, journal = {Toxicology Letters}, volume = {133}, number = {1}, year = {2002}, note = {ISI Document Delivery No.: 575QMTimes Cited: 46Cited Reference Count: 499th International Congress of ToxicologyJUL 08-12, 2001BRISBANE, AUSTRALIA}, month = {Jul}, pages = {47-57}, type = {Proceedings Paper}, abstract = {Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. With ascorbic acid the rate of iron release from HLF by DMA(V) was intermediate (3.37 nM/min, P < 0.05) and by DMA(III) was much higher (16.3 nM/min, P < 0.001). No pBR322 plasmid DNA damage was observed from in vitro exposure to arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)) or DMA(V) alone. DNA damage was observed following DMA(III) exposure; coexposure to DMA(III) and HLF caused more DNA damage; considerably higher amounts of DNA damage was caused by coexposure of DMA(III), HLF and ascorbic acid. Diethylenetriaminepentaacetic acid (an iron chelator), significantly inhibited DNA damage. Addition of catalase (which can increase Fe2+ concentrations) further increased the plasmid DNA damage. Iron-dependent DNA damage could be a mechanism of action of human arsenic carcinogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.}, keywords = {arsenic, BIOCHEMICAL PARAMETERS, CARCINOGENESIS, DIMETHYLARSINIC ACID, dimethylarsinous acid, DMA(111), DNA damage, ENDOTHELIAL-CELLS, human liver ferritin, INDUCTION, INORGANIC ARSENICS, iron, MICE, MONOMETHYLARSONOUS ACID, reactive oxygen, species, STRAND BREAKS}, isbn = {0378-4274}, url = {://000176959200005}, author = {Ahmad, S. and Kitchin, K. T. and Cullen, W. R.} } @article {5118, title = {Arsenic speciation in sea scallop gonads}, journal = {Applied Organometallic Chemistry}, volume = {15}, number = {6}, year = {2001}, note = {ISI Document Delivery No.: 435TUTimes Cited: 15Cited Reference Count: 19}, month = {Jun}, pages = {533-538}, type = {Article}, abstract = {The arsenic species in male and female sea scallop gonads (Placopecten magellanicus) at pre-spawning and post-spawning stages, collected near Newfoundland, Canada, were characterized by using high-performance liquid chromatography-inductively coupled plasma-mass spectrometry, All samples contain arsenobetaine (0.5-3.0 mug g(-1)) and a dimethylarsinoylriboside derivative as the major water-soluble arsenic compounds. Male pre-spawning gonads contain 0.35-2.4 mug g(-1) of the dimethylarsinoylriboside, Female pre-spawning gonads contain 0.47-9.64 mug g(-1) of the same compound. Postspawning gonads, both male and female, contain higher concentrations of this compound (3.7-11.4 mug g(-1)). The total concentrations of water-soluble arsenic compounds are different in male and female pre-spawning gonads. These differences are not obvious in post-spawning gonads. Post-spawning gonads contain higher total concentrations of water-soluble arsenic compounds than pre-spawning gonads. Copyright (C) 2001 John Wiley \& Sons, Ltd.}, keywords = {arsenic, arsenobetaine, arsenosugar, HEPATOCYTES, HPLC, ICP-MS, MONOMETHYLARSONOUS ACID, RAT, scallops, SPECIATION}, isbn = {0268-2605}, url = {://000168897900012}, author = {Lai, V. W. M. and Cullen, W. R. and Ray, S.} } @article {5144, title = {Methylated trivalent arsenic species are genotoxic}, journal = {Chemical Research in Toxicology}, volume = {14}, number = {4}, year = {2001}, note = {ISI Document Delivery No.: 424XZTimes Cited: 253Cited Reference Count: 55}, month = {Apr}, pages = {355-361}, type = {Article}, abstract = {The reactivities of methyloxoarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled phi X174 RFI DNA were assessed using a DNA nicking assay. The induction of DNA damage by these compounds in vitro in human peripheral lymphocytes was assessed using a single-cell gel (SCG, "comet") assay. Both methylated trivalent arsenicals were able to nick and/or completely degrade phi X174 DNA in vitro in 2 h incubations at 37 degreesC (pH 7.4) depending on concentration. MAsIII was effective at nicking phi X174 DNA at 30 mM; however, at 150 muM DMAsIII, nicking could be observed. Exposure of (phi X174 DNA to sodium arsenite (iAs(III); from 1 nM up to 300 mM), sodium arsenate (from 1 muM to 1 M), and the pentavalent arsenicals, monomethylarsonic acid (from 1 muM to 3 M) and dimethylarsinic acid (from 0.1 to 300 mM), did not nick or degrade phi X174 DNA under these conditions. In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent than any other arsenicals that were tested. On the basis of the slopes of the concentration-response curve for the tail moment in the SCG assay, MAsIII and DMAsIII were 77 and 386 times more potent than iAs(III), respectively. Because methylated trivalent arsenicals were the only arsenic compounds that were observed to damage naked DNA and required no exogenously added enzymatic or chemical activation systems, they are considered here to be direct-acting forms of arsenic that are genotoxic, though they are not, necessarily, the only genotoxic species of arsenic that could exist.}, keywords = {CELLS, DIMETHYLARSINIC ACID, DRINKING-WATER, ENZYMATIC METHYLATION, FIBROBLASTS, GLUTATHIONE-REDUCTASE, HUMAN, HUMAN URINE, INHIBITION, MONOMETHYLARSONOUS ACID, SODIUM ARSENITE}, isbn = {0893-228X}, url = {://000168260400005}, author = {Mass, M. J. and Tennant, A. and Roop, B. C. and Cullen, W. R. and Styblo, M. and Thomas, D. J. and Kligerman, A. D.} } @article {4862, title = {Determination of monomethylarsonous acid, a key arsenic methylation intermediate, in human urine}, journal = {Environmental Health Perspectives}, volume = {108}, number = {11}, year = {2000}, note = {ISI Document Delivery No.: 373XPTimes Cited: 101Cited Reference Count: 48}, month = {Nov}, pages = {1015-1018}, type = {Article}, abstract = {In this study we report on the finding of monomethylarsonous acid [MMA(III)I in human urine. This newly identified arsenic species is a key intermediate in the metabolic pathway of arsenic biomethylation, which involves stepwise reduction of pentavalent to trivalent arsenic species followed by oxidative addition of a methyl group. Arsenic speciation was carried out using ion-pair chromatographic separation of arsenic compounds with hydride generation atomic fluorescence spectrometry detection. Speciation of the inorganic arsenite [As(III)], inorganic arsenate [As(V)], monomethylarsonic acid [MMA(V)], dimethylarsinic acid [DMA(V)], and MMA(III) in a urine sample was complete in 5 min. Urine samples collected from humans before and after a single oral administration of 300 mg sodium 2,3-dimercapto-1-propane sulfonate (DMPS) were analyzed for arsenic species. MMA(III) was found in 51 out of 123 urine samples collected from 41 people in inner Mongolia 0-6 hr after the administration of DMPS. MMA(III)in urine samples did not arise from the reduction of MMA(V) by DMPS. DMPS probably assisted the release of MMA(III) that was formed in the body. Along with the presence of MMA(III), there was an increase in the relative concentration of MMA(V) and a decrease in DMA(V) in the urine samples collected after the DMPS ingestion.}, keywords = {3-dimercapto-1-propane sulfonate, ARSENIC SPECIATION, BIOMARKERS, CARCINOGENESIS, CHEMICAL FORMS, DIMETHYLARSINIC ACID, ENZYMATIC METHYLATION, EXCRETION, EXPOSURE, GLUTATHIONE-REDUCTASE, INGESTION, METABOLISM, METABOLITES, METHYLATION, MONOMETHYLARSONOUS ACID, sodium 2, SPECIATION, trivalent methylarsenic species, urine metabolites}, isbn = {0091-6765}, url = {://000165315600019}, author = {Le, X. C. and Ma, M. S. and Lu, X. F. and Cullen, W. R. and Aposhian, H. V. and Zheng, B. S.} } @article {4901, title = {Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes}, journal = {Toxicology and Applied Pharmacology}, volume = {163}, number = {2}, year = {2000}, note = {ISI Document Delivery No.: 295TBTimes Cited: 294Cited Reference Count: 28}, month = {Mar}, pages = {203-207}, type = {Article}, abstract = {Methylation has been considered to be the primary detoxication pathway of inorganic arsenic. Inorganic arsenic is methylated by many, but not all animal species, to monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), and dimethylarsinic acid (DMA(V)). The As-V derivatives have been assumed to produce low toxicity, but the relative toxicity of MMA(III) remains unknown. In vitro toxicities of arsenate, arsenite, MMA(V), MMA(III) and DMA(V) were determined in Chang human hepatocytes, Leakage of lactate dehydrogenase (LDH) and intracellular potassium (K+) and mitochondrial metabolism of the tetrazolium salt XTT were used to assess cytotoxicity due to arsenic exposure. The mean LC50 based on LDH assays in phosphate media was 6 mu M for MMA(III) and 68 mu M for arsenite. Using the assay for K+ leakage in phosphate media, the mean LC50 was 6.3 mu M for MMA(III) and 19.8 mu M for arsenite. The mean LC50 based on the XTT assay in phosphate media was 13.6 mu M for MMA(III) and 164 mu M for arsenite. The results of the three cytotoxicity assays (LDH, K+, and XTT) reveal the following order of toxicity in Chang human hepatocytes: MMA(III) > arsenite > arsenate > MMA(V) = DMA(V). Data demonstrate that MMA(III) an intermediate in inorganic arsenic methylation, is highly toxic and again raises the question as to whether methylation of inorganic arsenic is a detoxication process. (C) 2000 Academic Press.}, keywords = {ARSENATE, ARSENITE, ASSAY, CELLS, Chang human hepatocytes, DIMETHYLARSINIC ACID, DMA, DMA(V), DMPS, ENZYMATIC METHYLATION, LDH, LIVER, MICE, MMA(III), MMA(V), monomethylarsonic acid, MONOMETHYLARSONOUS ACID, POTASSIUM, VIABILITY, XTT}, isbn = {0041-008X}, url = {://000085983000013}, author = {Petrick, J. S. and Ayala-Fierro, F. and Cullen, W. R. and Carter, D. E. and Aposhian, H. V.} }