@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 {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 = {<Go to ISI>://000085983000013},
	author = {Petrick, J. S. and Ayala-Fierro, F. and Cullen, W. R. and Carter, D. E. and Aposhian, H. V.}
}
@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.}
}
@article {3289,
	title = {ARSENIC BIOMETHYLATION BY THE MICROORGANISM APIOTRICHUM HUMICOLA IN THE PRESENCE OF L-METHIONINE-METHYL-D(3)},
	journal = {Applied Organometallic Chemistry},
	volume = {9},
	number = {7},
	year = {1995},
	note = {ISI Document Delivery No.: TG189Times Cited: 15Cited Reference Count: 273rd International Conference on Environmental and Biological Aspects of Main Group Organometals (ICEBAMO 94)SEP, 1994BORDEAUX, FRANCESoc Francaise Chim, Royal Soc Chem, CNRS, EC Measurement \& Testing Program, French Minist Environm, French Minist Res \& Technol, Univ Bordeaux I, Univ Bordeaux II, IFREMER, INRA, Conseil Reg Aquitaine, Lyonnaise Eaux Dumez Water Co., Thermo Jarell Ash, John Wiley \& Sons, Freund Publ, Elsevier Sci Publ},
	month = {Nov},
	pages = {507-515},
	type = {Proceedings Paper},
	abstract = {The microorganism Apiotrichum humicola (previously known as Candida humicola) grown in the presence of either arsenate, arsenite, methyl-arsonic acid or dimethylarsinic acid, produces arsenic-containing metabolites in the growth medium. When L-methionine-methyl-d(3) is added to the cultures, the CD3 label is incorporated intact into the metabolites to a considerable extent to form deuterated dimethylarsenic and trimethylarsenic species, indicating that S-adenosylmethionine, or some related sulphonium compound, is involved in the biological methylation. Conclusive evidence of CD3 incorporation in the arsenicals found in the growth medium was provided by using a specially developed hydride generation-gas chromatography-mass spectrometry system (HG-GC-MS).},
	keywords = {ARSENATE, ARSENITE, CHROMATOGRAPHY MASS SPECTROMETRY, DIMETHYLARSINIC ACID, EXTRACELLULAR, GAS, HYDRIDE GENERATION, HYDRIDE GENERATION GAS, L-METHIONINE-METHYL-D(3), methylarsonic acid, METHYLATION, MICROORGANISM, REDUCTION, S-ADENOSYLMETHIONINE, THIOLS, TRIMETHYLARSINE OXIDE},
	isbn = {0268-2605},
	url = {<Go to ISI>://A1995TG18900002},
	author = {Cullen, W. R. and Li, H. and Pergantis, S. A. and Eigendorf, G. K. and Mosi, A. A.}
}
