@article {797,
	title = {Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar},
	journal = {Environmental Science \& Technology},
	volume = {38},
	number = {15},
	year = {2004},
	note = {ISI Document Delivery No.: 842WOTimes Cited: 23Cited Reference Count: 54},
	month = {Aug},
	pages = {4140-4148},
	type = {Article},
	abstract = {Seafood frequently contains high concentrations of arsenic (similar to10-100 mg/kg dry weight). In marine algae (seaweed), this arsenic occurs predominantly as ribose derivatives known collectively as arsenosugars. Although it is clear that arsenosugars are not acutely toxic, there is a possibility of arsenosugars having slight chronic toxicity. In general, trivalent arsenicals are more toxic than their pentavalent counterparts, so in this work we examine the hypothesis that trivalent arsenosugars might be significantly more toxic than pentavalent arsenosugars in vitro. We compared the in vitro toxicity of (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a pentavalent arsenosugar, to that of its trivalent counterpart, (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsino-beta-D- riboside. The trivalent arsenosugar nicked plasmid DNA, whereas the pentavalent arsenosugar did not. The trivalent arsenosugar was more cytotoxic (IC50 = 200 muM, 48 h exposure) than its pentavalent counterpart (IC50 > 6000 muM, 48 h exposure) in normal human epidermal keratinocytes in vitro as determined via the neutral red uptake assay. However, both the trivalent and the pentavalent arsenosugars were significantly less toxic than MMA(III), DMA(III), and arsenate. Neither the pentavalent arsenosugar nor the trivalent arsenosugar were mutagenic in Salmonella TA104. The trivalent arsenosugar was readily formed by reaction of the pentavalent arsenosugar with thiol compounds, including, cysteine, glutathione, and dithioerythritol. This work suggests that the reduction of pentavalent arsenosugars to trivalent arsenosugars in biology might have environmental consequences, especially because seaweed consumption is a significant environmental source for human exposure to arsenicals.},
	keywords = {DIMETHYLARSINIC ACID, DNA-DAMAGE, HUMAN-CELLS, IN-VITRO, INORGANIC ARSENICS, METABOLISM, METHYLATED ARSENICALS, MONOMETHYLARSONOUS ACID MMA(III), ORGANIC ARSENIC COMPOUNDS, SEAWEED},
	isbn = {0013-936X},
	url = {<Go to ISI>://000223035400022},
	author = {Andrewes, P. and Demarini, D. M. and Funasaka, K. and Wallace, K. and Lai, V. W. M. and Sun, H. S. and Cullen, W. R. and Kitchin, K. T.}
}
@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 {4717,
	title = {Arsenic species that cause release of iron from ferritin and generation of activated oxygen},
	journal = {Archives of Biochemistry and Biophysics},
	volume = {382},
	number = {2},
	year = {2000},
	note = {ISI Document Delivery No.: 367PNTimes Cited: 90Cited Reference Count: 61},
	month = {Oct},
	pages = {195-202},
	type = {Article},
	abstract = {The in vitro effects of four different species of arsenic (arsenate, arsenite, monomethylarsonic acid, and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinic acid (DMA((V))) and dimethylarsinous acid (DMA((III))) significantly released iron from horse spleen ferritin either with or without the presence of ascorbic acid, a strong synergistic agent. Ascorbic acid-mediated iron release was time-dependent as well as both (DMA((III))) and ferritin concentration-dependent. Iron release from ferritin by DMA((III)) alone or with ascorbic acid was not significantly inhibited by superoxide dismutase (150 or 300 units/ml). However, the iron release was greater under anaerobic conditions (nitrogen gas), which indicates direct chemical reduction of iron from ferritin by DMA((III)), with or without ascorbic acid. Both DMA((V)) and DMA((III)) released iron from both horse spleen and human liver ferritin. Further, the release of ferritin-iron by DMA((III)) with ascorbic acid catalyzed bleomycin-dependent degradation of calf thymus DNA. These results indicate that exogenous methylated arsenic species and endogenous ascorbic acid can cause (a) the release of iron from ferritin, (b) the iron-dependent formation of reactive oxygen species, and (c) DNA damage. This reactive oxygen species pathway could be a mechanism of action of arsenic carcinogenesis in man. (C) 2000 Academic Press.},
	keywords = {arsenic, ascorbic acid, BIOCHEMICAL PARAMETERS, DAMAGE, DIMETHYLARSINIC ACID, DNA-DAMAGE, ferritin, FREE-RADICALS, INORGANIC ARSENICS, iron, LIPID-PEROXIDATION, MAIN METABOLITE, OXIDATIVE, oxygen species, REACTIVE, reactive oxygen, VITAMIN-C},
	isbn = {0003-9861},
	url = {<Go to ISI>://000090070800005},
	author = {Ahmad, S. and Kitchin, K. T. and Cullen, W. R.}
}
@article {4389,
	title = {High-throughput assay for G(2) checkpoint inhibitors and identification of the structurally novel compound isogranulatimide},
	journal = {Cancer Research},
	volume = {58},
	number = {24},
	year = {1998},
	note = {ISI Document Delivery No.: 148HTTimes Cited: 83Cited Reference Count: 39},
	month = {Dec},
	pages = {5701-5706},
	type = {Article},
	abstract = {Treatment of cancer cells lacking p53 function with G(2) checkpoint inhibitors sensitizes them to the toxic effects of DNA damage and has been proposed as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously, We report the development of a G(2) checkpoint inhibition assay that is suitable for high-throughput screening and its application to a screen of 1300 natural extracts. We present the isolation of a new G(2) checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with gamma-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.},
	keywords = {ANTITUMOR DRUG, BHK CELLS, CAFFEINE, CELL-CYCLE CHECKPOINTS, DNA-DAMAGE, HELA-CELLS, mitosis, P34(CDC2) KINASE, P53 FUNCTION, PREMATURE, PROTEIN KINASE-C},
	isbn = {0008-5472},
	url = {<Go to ISI>://000077499800017},
	author = {Roberge, M. and Berlinck, R. G. S. and Xu, L. and Anderson, H. J. and Lim, L. Y. and Curman, D. and Stringer, C. M. and Friend, S. H. and Davies, P. and Vincent, I. and Haggarty, S. J. and Kelly, M. T. and Britton, R. and Piers, E. and Andersen, R. J.}
}
