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Identifying Androgen Disrupting Chemical Metabolites using Intracellular Xenobiotic mRNA Transfection Method
Citation:
Brown, Evan C., D. Hallinger, AND Steve Simmons. Identifying Androgen Disrupting Chemical Metabolites using Intracellular Xenobiotic mRNA Transfection Method. North Carolina Endocrine Disruptor Conference, Raleigh, NC, September 30, 2022. https://doi.org/10.23645/epacomptox.21493371
Impact/Purpose:
Poster presented to the North Carolina Endocrine Disruptor Conference September 2022 highlighting the effects of CYP metabolism on human AR bioactivity.
Description:
The existence of 10,000+ chemicals lacking thorough toxicity data necessitates the use of in vitro high-throughput screening (HTS) assays for hazard identification and chemical prioritization. A major limitation of existing high-throughput assays is their lack of endogenous cellular metabolism and subsequent inability to identify metabolically-induced changes in toxicity. As such, our laboratory developed an intracellular mRNA transfection method to confer Cytochrome P450 (CYP) metabolism to cell-based HTS assays. This method was developed to be applied to a wide-range of existing assay types; however, it had yet to be deployed on a cell-based HTS assay measuring an endocrine-related endpoint. Therefore, we sought to use our mRNA transfection method on a novel androgen receptor dimerization assay (AR2) to evaluate the effect of CYP metabolism on antagonists of the human androgen receptor. Identification of bio- activated or deactivated metabolites can better characterize a compound's interaction with the AR pathway, leading to improved hazard estimates. This abstract does not reflect EPA policy.
URLs/Downloads:
DOI: Identifying Androgen Disrupting Chemical Metabolites using Intracellular Xenobiotic mRNA Transfection Method
BROWN_AR_METABOLITES_POSTER_NCEDC22_V3.PDF (PDF, NA pp, 1033.908 KB, about PDF)