Selecting a minimal set of androgen receptor assays for screening chemicals.

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here we describe a revised mathematical modeling approach that also incorporates data from newly available assays and demonstrate that subsets of assays can provide close to the same level of predictivity. These subset models are evaluated against the full model using 1820 chemicals, as well as in vitro and in vivo reference chemicals from the literature. Agonist batteries of as few as six assays and antagonist batteries of as few as five assays can yield balanced accuracies of 95% or better relative to the full model. Balanced accuracy for predicting reference chemicals is 100%. An approach is outlined for researchers to develop their own subset batteries to accurately detect AR activity using assays that map to the pathway of key molecular and cellular events involved in chemical-mediated AR activation and transcriptional activity. This work indicates in vitro bioactivity and in silico predictions that map to the AR pathway could be used in an integrated approach to testing and assessment for identifying chemicals that interact directly with the mammalian AR. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Richard Judson, Keith Houck, Katie Paul Friedman, Jason Brown, Patience Browne, Paul A Johnston, David A Close, Kamel Mansouri, Nicole Kleinstreuer. Selecting a minimal set of androgen receptor assays for screening chemicals. Regulatory toxicology and pharmacology : RTP. 2020 Nov;117:104764

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PMID: 32798611

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