@article {929,
	title = {Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood},
	journal = {Chemical Research in Toxicology},
	volume = {17},
	number = {12},
	year = {2004},
	note = {ISI Document Delivery No.: 881XKTimes Cited: 45Cited Reference Count: 74},
	month = {Dec},
	pages = {1733-1742},
	type = {Article},
	abstract = {Four trivalent arsenic species, inorganic arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), and phenylarsine oxide ((PhAsO)-O-III), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the alpha and beta chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAs(III), MMA(III), and DMA(III) showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the alpha chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.},
	keywords = {ACUTE PROMYELOCYTIC LEUKEMIA, CULTURED HUMAN-CELLS, dimethylarsinous acid, DNA-DAMAGE, HUMAN URINE, METHYLATED METABOLITES, MONOMETHYLARSONOUS ACID MMA(III), TOXICITY, TRIOXIDE, TRIVALENT},
	isbn = {0893-228X},
	url = {<Go to ISI>://000225902600023},
	author = {Lu, M. L. and Wang, H. L. and Li, X. F. and Lu, X. F. and Cullen, W. R. and Arnold, L. L. and Cohen, S. M. and Le, X. C.}
}
@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 = {<Go to ISI>://000176959200005},
	author = {Ahmad, S. and Kitchin, K. T. and Cullen, W. R.}
}
@article {4942,
	title = {Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells},
	journal = {Archives of Toxicology},
	volume = {74},
	number = {6},
	year = {2000},
	note = {ISI Document Delivery No.: 349ZATimes Cited: 358Cited Reference Count: 37},
	month = {Aug},
	pages = {289-299},
	type = {Article},
	abstract = {Biomethylation is considered a major detoxification pathway for inorganic arsenicals (iAs). According to the postulated metabolic scheme, the methylation of iAs yields methylated metabolites in which arsenic is present in both pentavalent and trivalent forms. Pentavalent mono- and dimethylated arsenicals are less acutely toxic than iAs. However, little is known about the toxicity of trivalent methylated species. In the work reported here the toxicities of iAs and trivalent and pentavalent methylated arsenicals were examined in cultured human cells derived from tissues that are considered a major site for iAs methylation (liver) or targets for carcinogenic effects associated with exposure to iAs (skin, urinary bladder, and lung). To characterize the role of methylation in the protection against toxicity of arsenicals, the capacities of cells to produce methylated metabolites were also examined. In addition to human cells, primary rat hepatocytes were used as methylating controls. Among the arsenicals examined, trivalent monomethylated species were the most cytotoxic in all cell types. Trivalent dimethylated arsenicals were at least as cytotoxic as trivalent iAs (arsenite) for most cell types. Pentavalent arsenicals were significantly less cytotoxic than their trivalent analogs. Among the cell types examined, primary rat hepatocytes exhibited the greatest methylation capacity for iAs followed by primary human hepatocytes, epidermal keratinocytes, and bronchial epithelial cells. Cells derived from human bladder did not methylate iAs. There was no apparent correlation between susceptibility of cells to arsenic toxicity and their capacity to methylate iAs. These results suggest that (1) trivalent methylated arsenicals, intermediary products of arsenic methylation, may significantly contribute to the adverse effects associated with exposure to iAs, and (2) high methylation capacity does not protect cells from the acute toxicity of trivalent arsenicals.},
	keywords = {ARSENATE, arsenic, ARSENITE, BINDING, bladder, cell culture, CELLULAR UPTAKE, DIMETHYLARSINIC ACID, dimethylarsinous acid, DRINKING-WATER, ENZYMATIC METHYLATION, GLUTATHIONE, HEPATOCYTES, HUMAN, IN-VITRO METHYLATION, LIVER, lung, METABOLISM, methylarsonic acid, methylarsonous acid, METHYLATION, RABBIT LIVER, SKIN, TOXICITY},
	isbn = {0340-5761},
	url = {<Go to ISI>://000089074500001},
	author = {Styblo, M. and Del Razo, L. M. and Vega, L. and Germolec, D. R. and LeCluyse, E. L. and Hamilton, G. A. and Reed, W. and Wang, C. and Cullen, W. R. and Thomas, D. J.}
}
@article {4552,
	title = {The separation of dimethylarsinic acid, methylarsonous acid, methylarsonic acid, arsenate and dimethylarsinous acid on the Hamilton PRP-X100 anion-exchange column},
	journal = {Applied Organometallic Chemistry},
	volume = {13},
	number = {11},
	year = {1999},
	note = {ISI Document Delivery No.: 255DLTimes Cited: 24Cited Reference Count: 29},
	month = {Nov},
	pages = {837-843},
	type = {Article},
	abstract = {In order to separate the potential arsenite metabolites methylarsonous acid and dimethylarsinous acid from arsenite, arsenate, methylarsonic acid and dimethylarsinic acid, the pH-dependent retention behaviour of all six arsenic compounds was studied on a Hamilton PRP-X100 anion-exchange column with 30 mM phosphate buffers (pH 5, 6, 7, 8 and 9) containing 20\% (v/v) methanol as mobile phase and employing an inductively coupled plasma atomic emission spectrometer (ICP-AES) as the arsenic-specific detector. Baseline separation of dimethylarsinic acid, methylarsonous acid, methylarsonic acid, arsenate and dimethylarsinous acid was achieved with a 30 mmol dm(-3) phosphate buffer (pH 5)-methanol mixture (80:20, v/v) in 25 min. Arsenite is not baseline-separated from dimethylarsinic acid under these conditions, Copyright (C) 1999 John Wiley \& Sons, Ltd.},
	keywords = {ARSENATE, ARSENITE, BEHAVIOR, DIMETHYLARSINIC ACID, dimethylarsinous acid, ENVIRONMENT, ENZYMATIC METHYLATION, GLUTATHIONE, HPLC-ICP-AES, LAKE-BIWA, METABOLISM, METHYLARSENICALS, methylarsonic acid, methylarsonous acid, SPECIATION, SPECTROMETRY},
	isbn = {0268-2605},
	url = {<Go to ISI>://000083654200005},
	author = {Gailer, J. and Madden, S. and Cullen, W. R. and Denton, M. B.}
}
