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基于电化学催化DNA氧化的化学物质毒性和氧化应激传感器。

Sensors for toxicity of chemicals and oxidative stress based on electrochemical catalytic DNA oxidation.

作者信息

Rusling James F

机构信息

Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.

出版信息

Biosens Bioelectron. 2004 Nov 15;20(5):1022-8. doi: 10.1016/j.bios.2004.06.033.

DOI:10.1016/j.bios.2004.06.033
PMID:15530799
Abstract

Films of DNA, enzymes, polyions, and catalytic redox polyions of nanometer thickness on electrodes can provide active elements for sensors for screening the toxicity of chemicals and their metabolites, and for oxidative stress. The unifying feature of this approach involves layer-by-layer electrostatic assembly of films designed to detect DNA damage. Films containing DNA and enzymes enable detection of structural damage to DNA as a basis for toxicity screening. These films bioactivate chemicals to their metabolites, which can then react with DNA, mimicking toxicity pathways in the human liver. Metallopolyions that catalyze DNA oxidation can be incorporated into DNA/enzyme films leading to "reagentless" sensors. These sensors are suitable for detecting relative DNA damage rates in <5 min of the enzyme reactions. Films of the osmium polymer Os(bpy)(2)(PVP)(10)Cl [poly(vinylpyridine), PVP] can be used to monitor DNA oxidation selectively. Such films may be applicable to determination of oxidized DNA as a clinical biomarker for oxidative stress. Inclusion of the analogous ruthenium metallopolymer in the sensor provides a monitor for oxidation of other nucleobases.

摘要

电极上纳米厚度的DNA、酶、聚离子和催化氧化还原聚离子薄膜可为筛选化学物质及其代谢产物的毒性以及氧化应激的传感器提供活性元件。这种方法的统一特性涉及用于检测DNA损伤的薄膜的逐层静电组装。含有DNA和酶的薄膜能够检测DNA的结构损伤,以此作为毒性筛选的基础。这些薄膜将化学物质生物激活为其代谢产物,然后代谢产物可与DNA反应,模拟人类肝脏中的毒性途径。催化DNA氧化的金属聚离子可掺入DNA/酶薄膜中,从而形成“无试剂”传感器。这些传感器适用于在酶反应的5分钟内检测相对DNA损伤率。锇聚合物Os(bpy)(2)(PVP)(10)Cl [聚乙烯基吡啶,PVP]薄膜可用于选择性监测DNA氧化。此类薄膜或许可用于将氧化DNA测定为氧化应激的临床生物标志物。在传感器中加入类似的钌金属聚合物可监测其他核碱基的氧化。

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