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Retrofit Strategies for the Incorporation of Metabolic Competence into In Vitro Assays
Citation:
DeGroot, D., R. Thomas, Steve Simmons, AND C. Deisenroth. Retrofit Strategies for the Incorporation of Metabolic Competence into In Vitro Assays. Presented at Society of Toxicology Annual Meeting, Baltimore, MD, March 10 - 14, 2019.
Impact/Purpose:
Abstract submitted for SOT 2019 session proposal on Practical Applications of Non-Animal Methods in the Food Industry.
Description:
The US EPA’s ToxCast program assesses chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which can lead to mischaracterization of chemical hazard (e.g., the parent compound is detoxified or bioactivated in vivo). The Alginate Immobilization of Metabolic Enzymes (AIME) platform retrofits existing HTS assays with metabolic competence by attaching alginate-encapsulated hepatic S9 microspheres to supports extending from microplate lids. Current efforts have focused on coupling the AIME platform with the VM7Luc4E2 estrogen receptor (ER) transactivation assay which is an OECD approved method for the detection of ER agonists and antagonists. The AIME method and the results of a pilot chemical screen using the VM7Luc4E2-AIME platform will be discussed in the context of challenges facing implementation of metabolic competence to HTS assays. This abstract does not necessarily reflect the policy of the US EPA.