@article {647,
	title = {Interaction of trivalent axsenicals with metallothionein},
	journal = {Chemical Research in Toxicology},
	volume = {16},
	number = {7},
	year = {2003},
	note = {ISI Document Delivery No.: 702UQTimes Cited: 53Cited Reference Count: 625th International Conference on Arsenic Exposure and Health EffectsJUL 14-18, 2002SAN DIEGO, CALIFORNIA},
	month = {Jul},
	pages = {873-880},
	type = {Proceedings Paper},
	abstract = {Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data are available on arsenic-containing proteins in biological systems. This study reports on arsenic interaction with metallothionein and established binding stoichiometries between metallothionein and the recently discovered trivalent metabolites of arsenic metabolism. Size exclusion chromatography with inductively coupled plasma mass spectrometry analysis of reaction mixtures between trivalent arsenicals and metallothionein clearly demonstrated the formation of complexes of arsenic with metallothionein. Analysis of the complexes using electrospray quadrupole time-of-flight tandem mass spectrometry revealed the detailed binding stoichiometry between arsenic and the 20 Cys residues in the metallothionein molecule. Inorganic arsenite (As-III) and its two trivalent methylation metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), readily bind with metallothionein. Each metallothionein molecule could bind with up to six As-III, 10 MMA(III), and 20 DMA(III) molecules, consistent with the coordination chemistry of these arsenicals. The findings on arsenic interaction with proteins are useful for a better understanding of arsenic health effects.},
	keywords = {ARSENIC METABOLITES, ENZYMATIC METHYLATION, GLUTATHIONE-REDUCTASE, HUMAN URINE, INORGANIC ARSENICALS, MONOMETHYLARSONOUS ACID MMA(III), PYRUVATE-DEHYDROGENASE, RABBIT LIVER, THIOREDOXIN REDUCTASE, TOXICITY},
	isbn = {0893-228X},
	url = {<Go to ISI>://000184243200009},
	author = {Jiang, G. F. and Gong, Z. L. and Li, X. F. and Cullen, W. R. and Le, X. C.}
}
@article {5083,
	title = {Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid},
	journal = {Journal of Analytical Atomic Spectrometry},
	volume = {16},
	number = {12},
	year = {2001},
	note = {ISI Document Delivery No.: 498MYTimes Cited: 95Cited Reference Count: 52},
	pages = {1409-1413},
	type = {Article},
	abstract = {Two key arsenic metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), have recently been detected in human urine. There is an increasing interest in the speciation of these metabolites in humans because of their demonstrated effects on cellular toxicity and DNA damage. However, there is no information on the oxidative stability of these arsenic species. It is not known whether and to what extent these trivalent metabolites are changed during sample handling and storage. The objective of this study was to demonstrate the oxidative conversion of these arsenic species during sample storage. We compared the effects of the storage temperature (25, 4, and -20 degreesC) and storage duration (up to 5 months) on the stability of MMA(III) and DMA(III) in de-ionized water and in human urine. We used HPLC with hydride generation atomic fluorescence detection for the speciation of arsenic. This method provided sub-mug L-1 to low-mug L-1 detection limits for each arsenic species. We found that the oxidation of MMA(III) and DMA(III) was matrix and temperature dependent. Low temperature conditions (4 and -20 degreesC) improved the stability of these arsenic species over the room temperature storage condition. MMA(III) in de-ionized water was relatively stable for almost 4 months, when stored at 4 or -20 degreesC with less than 10\% of MMA(III) oxidized to MMA(V). In contrast, most of MMA(III) ( 90\%) in urine was oxidized to MMA(V) over the 5 month period under the 4 or -20 degreesC storage condition. At 25 degreesC, MMA(III) in urine was completely oxidized to MMA(V) within a week. DMA(III) in deionized water was stable for only 2-3 days, being rapidly oxidized to DMA(V). DMA(III) in urine was completely oxidized to DMA(V) within a day at 4 or -20 degreesC. The conversion of DMA(III) to DMA(V) in urine at 25 degreesC was complete in 17 h. These results show that MMA(III) and DMA(III) are much less stable than other arsenic species, and their stability depends on sample matrix and temperature.},
	keywords = {ATOMIC FLUORESCENCE DETECTION, BLACKFOOT DISEASE, chemical, DRINKING-WATER, ENZYMATIC, GLUTATHIONE-REDUCTASE, HUMAN HEPATOCYTES, HUMAN URINE, LIQUID-CHROMATOGRAPHY, METHYLATION, RABBIT LIVER, SPECIATION},
	isbn = {0267-9477},
	url = {<Go to ISI>://000172516100011},
	author = {Gong, Z. L. and Lu, X. F. and Cullen, W. R. and Le, X. C.}
}
@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.}
}
