Oxidative activation of the human carcinogen chromate by arsenite: a model for synergistic metal activation leading to oxidative DNA damage.
Oxidative activation of the human carcinogen chromate by arsenite: a model for synergistic metal activation leading to oxidative DNA damage.
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亚砷酸盐氧化激活人类致癌物铬酸盐：导致氧化性 DNA 损伤的协同金属激活模型。
DOI：
10.1016/j.tiv.2004.03.001
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Martin,BrookeD
中科院分区：
文献类型：
--
作者：
Sugden,KentD;Rigby,KevinM;Martin,BrookeD
人类接触有毒金属和类金属的环境很少发生从一个单一的纯化合物。大多数环境接触情况是不均匀的，同时接触多种有毒金属物质。在复杂的混合物中共同接触金属和准金属可导致协同、相加或甚至消耗性毒性反应。由于金属混合物相互作用的复杂性，需要采用方便和灵敏的方法来确定这种共同接触的潜在毒性反应。我们研究了两种常见的有毒金属铬酸盐Cr（VI）和亚砷酸盐As（III）之间的反应，以及As（III）还原激活Cr（VI）产生氧化应激和DNA损伤的能力。使用基于DCF的荧光染料测定，我们已经证明，As（III）和Cr（VI）之间的氧化还原反应产生高氧化性的铬，Cr（V）的高价中间体。这种氧化电位的诱导是剂量依赖性的，并且不发生与砷（III）或铬（VI）单独或与其他主要氧化态的砷，砷酸盐，砷（V）。在该反应中，DCFH氧化成荧光物质DCF的机制是通过直接的基于金属的氧化，因为自由基清除剂的加入没有显著降低该系统中染料的氧化。在铬酸盐和亚砷酸盐混合物中加入稳定高价Cr（V）氧化态的配体2-乙基-2-羟基丁酸（EHBA），导致DCF荧光增强。还发现用Cr（VI）和As（III）混合物观察到的DCF荧光与通过质粒切口测定测量的氧化DNA损伤相关。这些数据显示了环境混合物中的金属-金属相互作用如何导致氧化应激和DNA损伤的协同诱导。此外，这些数据证明了DCF荧光测定作为筛选金属混合物中协同氧化还原相互作用的灵敏方法的实用性。
Human exposure to toxic metals and metalloids in the environment seldom occurs from a single pure compound. Most environmental exposure profiles are heterogeneous with co-exposure occurring coincident with multiple toxic metal species. This co-exposure to metals and metalloids in complex mixtures can result in a synergistic, additive or even depletive toxic response. The complexity of interactions presented by metal mixtures presents a need for convenient and sensitive methods to determine potential toxic responses from such co-exposure. We have studied the reaction between the two commonly associated toxic metals of chromate, Cr(VI), and arsenite, As(III), with regards to the ability of As(III) to reductively activate Cr(VI) to generate oxidative stress and DNA damage. Using a DCF-based fluorescent dye assay we have demonstrated that the redox reaction between As(III) and Cr(VI) yields high valent intermediates of chromium, Cr(V), that are highly oxidizing. This induction of oxidizing potential was dose dependent and did not occur with As(III) or Cr(VI) alone or, with the other major oxidation state of arsenic, arsenate, As(V). The mechanism of oxidation of DCFH to the fluorescent species, DCF, in this reaction was through a direct, metal-based oxidation since addition of radical scavengers did not significantly decrease oxidation of the dye in this system. The addition of a ligand that stabilizes the high valent Cr(V) oxidation state, 2-ethyl-2-hydroxybutyric acid (EHBA), to the chromate and arsenite mixture resulted in an enhancement of DCF fluorescence. The DCF fluorescence observed with the Cr(VI) and As(III) mixture was also found to correlate with oxidative DNA damage as measured by a plasmid nicking assay. These data show how metal–metal interactions in environmental mixtures could result in the synergistic induction of oxidative stress and DNA damage. Further, these data demonstrate the utility of the DCF fluorescence assay as a sensitive method for screening synergistic redox interactions in metal mixtures.
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DOI：
10.1007/bfb0111319
发表时间：
1983
期刊：
--
影响因子：
--
作者：
P. Connett;K. Wetterhahn
通讯作者：
P. Connett;K. Wetterhahn
影响因子：
15
作者：
CONNETT, PH;WETTERHAHN, KE
通讯作者：
WETTERHAHN, KE
影响因子：
4.1
作者：
Sugden, KD;Wetterhahn, KE
通讯作者：
Wetterhahn, KE
在细木工车间使用浸渍木材时，职业性接触铬、铜和砷。
DOI：
10.1093/annhyg/36.5.509
发表时间：
1992
期刊：
The Annals of occupational hygiene
影响因子：
--
作者：
Olle Nygren;Carl;Roger Lindahl
通讯作者：
Roger Lindahl
影响因子：
4.1
作者：
Petrick, JS;Jagadish, B;Aposhian, HV
通讯作者：
Aposhian, HV