@article {465,
	title = {DNA damage induced by methylated trivalent arsenicals is mediated by reactive oxygen species},
	journal = {Chemical Research in Toxicology},
	volume = {15},
	number = {12},
	year = {2002},
	note = {ISI Document Delivery No.: 627VUTimes Cited: 104Cited Reference Count: 48},
	month = {Dec},
	pages = {1627-1634},
	type = {Article},
	abstract = {Arsenic is a human carcinogen; however, the mechanisms of arsenic{\textquoteright}s induction of carcinogenic effects have not been identified clearly. We have shown previously that monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) are genotoxic and can damage supercoiled phiX174 DNA and the DNA in peripheral human lymphocytes in culture. These trivalent arsenicals are biomethylated forms of inorganic arsenic and have been detected in the urine of subjects exposed to arsenite and arsenate. We show here by molecular, chemical, and physical methods that reactive oxygen species (ROS) are intermediates in the DNA-damaging activities of MMA(III) and DMA(III). Using the phiX174 DNA nicking assay we found that the ROS inhibitors Tiron, melatonin, and the vitamin E analogue Trolox inhibited the DNA-nicking activities of both MMA(III) and DMA(III) at low micromolar concentrations. The spin trap agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) also was effective at preventing the DNA nicking induced by MMA(III) and DMA(III.) ESR spectroscopy studies using DMPO identified a radical as a ROS intermediate in the DNA incubations with DMA(III). This radical adduct was assigned to the DMPO-hydroxyl free radical adduct on the basis of comparison of the observed hyperfine splitting constants and line widths with those reported in the literature. The formation of the DMPO-hydroxyl free radical adduct was dependent on time and the presence of DMA(III) and was completely inhibited by Tiron and Trolox and partially inhibited by DMSO. Using electrospray mass spectrometry, micromolar concentrations of DMA(v) were detected in the DNA incubation mixtures with DMA(III). These data are consistent with the conclusions that the DNA-damaging activity of DMA(III) is an indirect genotoxic effect mediated by ROS-formed concomitantly with the oxidation of DMA(III) to DMA(v).},
	keywords = {DIMETHYLARSINIC ACID, DRINKING-WATER, ENZYMATIC METHYLATION, FREE-RADICALS, HEPATOCYTES, HUMAN, HUMAN URINE, MALE F344 RATS, MONOMETHYLARSONOUS ACID MMA(III), ORAL-EXPOSURE, RAT-LIVER CYTOSOL},
	isbn = {0893-228X},
	url = {<Go to ISI>://000179957500017},
	author = {Nesnow, S. and Roop, B. C. and Lambert, G. and Kadiiska, M. and Mason, R. P. and Cullen, W. R. and Mass, M. J.}
}
@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 = {<Go to ISI>://000168897900012},
	author = {Lai, V. W. M. and Cullen, W. R. and Ray, S.}
}
@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.}
}
