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Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar

TitleDo arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar
Publication TypeJournal Article
Year of Publication2004
AuthorsAndrewes, P, Demarini, DM, Funasaka, K, Wallace, K, Lai, VWM, Sun, HS, Cullen, WR, Kitchin, KT
JournalEnvironmental Science & Technology
Volume38
Pagination4140-4148
Date PublishedAug
Type of ArticleArticle
ISBN Number0013-936X
KeywordsDIMETHYLARSINIC ACID, DNA-DAMAGE, HUMAN-CELLS, IN-VITRO, INORGANIC ARSENICS, METABOLISM, METHYLATED ARSENICALS, MONOMETHYLARSONOUS ACID MMA(III), ORGANIC ARSENIC COMPOUNDS, SEAWEED
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.

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