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Retrofit Strategies for Incorporating Xenobiotic Metabolism into High Throughput Screening Assays (EMGS)
Citation:
Simmons, Steve. Retrofit Strategies for Incorporating Xenobiotic Metabolism into High Throughput Screening Assays (EMGS). Presented at 48th Annual Meeting of the Environmental Mutagenesis and Genomics Society, Raleigh, NC, September 09 - 13, 2017.
Impact/Purpose:
Presentation to address the 48th Annual Meeting of the Environmental Mutagenesis and Genomics Society (EMGS) as aprt of symposium entitled: "New Approaches and Considerations for Assessing Chemical Safety in a Computational and a High-Throughput in Vitro Toxicology World". Disclaimer: This presentation does not necessarily reflect the policy of the US EPA.
Description:
The US EPA’s ToxCast program is designed to assess 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 could lead to a mischaracterization of chemical hazard if the parent compound is detoxified or bioactivated in vivo. The Alginate Immobilization of Metabolic Enzymes (AIME) platform is an HTS-compatible, retrofit solution that addresses this problem by immobilizing metabolically-active alginate microspheres to solid supports extending from custom microplate lids. By encapsulating the hepatic S9 fraction in the alginate microspheres, cytotoxicity and assay interference associated with direct addition of S9 is reduced. The AIME platform has been evaluated using luminescent cytochrome P450 substrates and is currently being piloted using various deployment strategies to optimize the coupling with existing ToxCast HTS assays. This abstract does not necessarily reflect the policy of the US EPA.