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

被引:92
作者
Andrewes, P
Demarini, DM
Funasaka, K
Wallace, K
Lai, VWM
Sun, HS
Cullen, WR
Kitchin, KT [1 ]
机构
[1] US EPA, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA
[2] Osaka City Inst Publ Hlth & Environm Sci, Dept Atmospher Environm, Osaka 543, Japan
[3] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada
关键词
D O I
10.1021/es035440f
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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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页码:4140 / 4148
页数:9
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