Dose-Dependent Transcriptomic Approach for Mechanistic Screening in Chemical Risk Assessment

Abstract

Omics approaches can monitor responses and alterations of biological pathways at a genome scale, which are useful to predict potential adverse effects from environmental toxicants. However, high-throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of “standardized” toxicogenomic methods. Here, we have developed a reduced transcriptome approach as an alternative strategy to facilitate testing a wide range of chemical concentrations, which targets a reduced set of genes to focus on key toxic response genes and associated pathways. The reduced transcriptomic approach allows full dose range testing of hundreds of chemicals or mixtures using human cells or zebrafish embryos. Points of departure of genes and pathways can be used for potency ranking and to classify chemicals by disrupted biological pathways. It is anticipated that reduced transcriptomic approaches will significantly advance pathway-based high-throughput screening of potentially toxic substances.