Screening Genotoxicity Chemistry with Microfluidic Electrochemiluminescent Arrays.

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. Genotoxicity 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.