Optimized Hydride Generation Systems for Arsenic Specia*

针对砷化物优化的氢化物发生系统*

基本信息

批准号：
7090023
负责人：
Miroslav Styblo
金额：
$ 3.94万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7090023
关键词：
Czech Republic analytical chemistry animal tissue arsenic atomic absorption spectrometry biomedical equipment development environmental exposure fluorescence spectrometry human tissue liver cells liver metabolism metal metabolism method development methylation miniature biomedical equipment thin layer chromatography tissue /cell culture urinalysis

项目摘要

DESCRIPTION (provided by applicant) The proposed FIRCA project will be carried out primarily in the Institute of Analytical Chemistry in Prague, Czech Republic, in collaboration with Dr. Jiri Dedina as an extension of NIH Grant 1 R01 ES010845. The metabolism of inorganic arsenic (iAs) in humans involves reduction and methylation reactions that produce methylated trivalent and pentavalent arsenicals. The liver is likely the major site for methylation of iAs in human body. The methylated trivalent arsenicals, unlike their pentavalent counterparts, are more potent than iAs as cytotoxins, genotoxins, enzyme inhibitors, and as modulators of major signal transduction pathways in human cells. Thus, formation of these species in the methylation pathway for iAs is often regarded as a mechanism for activation of this metalloid as a toxin and carcinogen. The interindividual variations in the capacity of the liver to methylate iAs may underlie differences in the susceptibility of individuals to toxic and carcinogenic effects associated with acute and chronic exposures to iAs. The proposed FIRCA project is an extension of the parent NIH-funded project that examines qualitative and quantitative aspects of the interindividual variations in the metabolism of iAs in human hepatic tissue and in primary human hepatocytes obtained from a significant number of donors. In the parent project, trivalent and pentavalent metabolites of iAs are analyzed in tissues and in hepatocyte cultures exposed to various concentrations of iAs, using the oxidation state specific hydride-generation (HG)-atomic absorption spectrometry (AAS). This method is uniquely suited for the speciation analysis of arsenic in complex biological matrices. However, it lacks sensitivity that is required for analysis of small amounts of metabolites generated under conditions of low iAs exposures. The goal of the proposed FIRCA project is to optimize the HG methodology and instrumentation to increase sensitivity of the arsenic speciation analyses by AAS or by atomic fluorescence spectrometry. The optimized HG systems will then be used in the parent project for analysis of metabolites produced by human hepatocytes exposed to low concentrations of iAs that are consistent with chronic environmental exposures. Importantly, the ultimate goal of the proposed research is to further improve the capacity of widely-used HG-based analytical techniques to analyze iAs metabolites, particularly the toxic methylated trivalent intermediates, in body fluids and tissues of individuals exposed to low concentrations of iAs from the environment.

描述（由申请人提供）拟议的FIRCA项目将主要在捷克共和国布拉格的分析化学研究所与Jiri Dedina博士合作，作为NIH Grant 1 R01 ES010845的延伸。人类中无机砷（IAS）的代谢涉及减少和产生甲基化三价和五价砷的甲基化反应。肝脏可能是人体IAS甲基化的主要部位。与五价同等的甲基化三价砷相比，甲基化的三价砷比IAS比IAS更有效，因为细胞毒素，基因毒素，酶抑制剂以及人类细胞中主要信号转导途径的主要信号转导途径的调节剂。因此，在IAS的甲基化途径中形成这些物种通常被视为激活该金属素作为毒素和致癌物的机制。肝脏IAS甲基化IAS能力的个体差异可能是个体对与IAS急性和慢性暴露有关的毒性和致癌作用的敏感性的差异。拟议的FIRCA项目是由父母NIH资助的项目的扩展，该项目研究了人类肝组织中IAS代谢的定性和定量方面以及从大量捐赠者获得的原发性人类肝细胞中的定性和定量方面。在母体项目中，使用氧化态特异性氢化物生成（HG） - 原子吸收光谱法（AAS），在组织和肝细胞培养物中分析了IAS的三价和五价代谢产物。该方法独特地适合复杂生物矩阵中砷的形成分析。但是，它缺乏敏感性，这是分析在低IAS暴露条件下产生的少量代谢产物所必需的。提出的FIRCA项目的目的是优化HG方法和仪器，以提高AAS或原子荧光光谱法对砷形成分析的灵敏度。然后，优化的HG系统将用于母体项目中，以分析由暴露于与慢性环境暴露一致的低浓度IAS的人肝细胞产生的代谢产物。重要的是，拟议的研究的最终目标是进一步提高广泛使用的基于HG的分析技术的能力，以分析IAS代谢物，尤其是在暴露于环境中低浓度IAS的个体的人体流体和组织中的有毒甲基化三价中间体。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

DOI：
10.1289/ehp.11503
发表时间：
2008-12
期刊：
Environmental health perspectives
影响因子：
10.4
作者：
Hernández-Zavala A;Valenzuela OL;Matousek T;Drobná Z;Dĕdina J;García-Vargas GG;Thomas DJ;Del Razo LM;Stýblo M
通讯作者：
Stýblo M

On-line pre-reduction of pentavalent arsenicals by thioglycolic acid for speciation analysis by selective hydride generation-cryotrapping-atomic absorption spectrometry.