微流控电化学发光阵列筛选遗传毒性化学物质。

Screening Genotoxicity Chemistry with Microfluidic Electrochemiluminescent Arrays.

机构信息

Department of Chemistry, University of Connecticut, Storrs, CT 06269, USA.

Department of Surgery and Neag Cancer Center, University of Connecticut Health Center, Farmington, CT 06032, USA.

出版信息

Sensors (Basel). 2017 May 3;17(5):1008. doi: 10.3390/s17051008.

DOI:10.3390/s17051008

PMID:28467352

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5469531/

Abstract

This review describes progress in the development of electrochemiluminescent (ECL) arrays aimed at sensing DNA damage to identify genotoxic chemistry related to reactive metabolites. refers to chemical or photochemical processes that damage DNA with toxic consequences. Our arrays feature DNA/enzyme films that form reactive metabolites of test chemicals that can subsequently react with DNA, thus enabling prediction of genotoxic chemical reactions. These high-throughput ECL arrays incorporating representative cohorts of human metabolic enzymes provide a platform for determining chemical toxicity profiles of new drug and environmental chemical candidates. The arrays can be designed to identify enzymes and enzyme cascades that produce the reactive metabolites. We also describe ECL arrays that detect oxidative DNA damage caused by metabolite-mediated reactive oxygen species. These approaches provide valuable high-throughput tools to complement modern toxicity bioassays and provide a more complete toxicity prediction for drug and chemical product development.

摘要

本文综述了电化学发光（ECL）阵列在检测 DNA 损伤方面的进展，旨在识别与反应性代谢物相关的遗传毒性化学物质。遗传毒性是指具有毒性后果的化学或光化学过程对 DNA 的损伤。我们的阵列具有 DNA/酶膜，可形成测试化学物质的反应性代谢物，随后可与 DNA 反应，从而能够预测遗传毒性化学反应。这些包含代表性人类代谢酶群体的高通量 ECL 阵列为确定新药物和环境化学候选物的化学毒性特征提供了平台。这些阵列可以设计用于识别产生反应性代谢物的酶和酶级联。我们还描述了检测代谢物介导致活性氧引起的氧化 DNA 损伤的 ECL 阵列。这些方法提供了有价值的高通量工具，可补充现代毒性生物测定，并为药物和化学产品开发提供更完整的毒性预测。