scholarly journals Screening for androgen agonists using autonomously bioluminescent HEK293 reporter cells

BioTechniques ◽  
2021 ◽  
Author(s):  
Tingting Xu ◽  
Madison Gilliam ◽  
Gary Sayler ◽  
Steven Ripp ◽  
Dan Close

Due to the public health concerns of endocrine-disrupting chemicals, there is an increasing demand to develop improved high-throughput detection assays for enhanced exposure control and risk assessment. A substrate-free, autobioluminescent HEK293ARE/Gal4-Lux assay was developed to screen compounds for their ability to induce androgen receptor (AR)-mediated transcriptional activation. The assay was validated against a group of 40 recommended chemicals and achieved an overall 87.5% accuracy in qualitatively classifying positive and negative AR agonists. The HEK293ARE/Gal4-Lux assay was demonstrated as a suitable tool for Tier 1 AR agonist screening. By eliminating exogenous substrate, this assay provided a significant advantage over traditional reporter assays by enabling higher-throughput screening with reduced testing costs while maintaining detection accuracy.

2020 ◽  
Vol 35 (3) ◽  
pp. 245-256
Author(s):  
Ann M. Vuong ◽  
Kimberly Yolton ◽  
Joseph M. Braun ◽  
Bruce P. Lanphear ◽  
Aimin Chen

AbstractBackgroundEpidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and nutrients may result in additive, synergistic, antagonistic, or potentiating effects on neurological endpoints. Investigating the impact of environmentally-relevant chemical mixtures, including heavy metals and endocrine disrupting chemicals (EDCs), is more reflective of human exposures and may result in more refined environmental policies to protect the public.ObjectiveIn this review, we provide a summary of epidemiological studies that have analyzed chemical mixtures of heavy metals and EDCs and neurobehavior utilizing multi-chemical models, including frequentist and Bayesian methods.ContentStudies investigating chemicals and neurobehavior have the opportunity to not only examine the impact of chemical mixtures, but they can also identify chemicals from a mixture that may play a key role in neurotoxicity, investigate interactive effects, estimate non-linear dose response, and identify potential windows of susceptibility. The examination of neurobehavioral domains is particularly challenging given that traits emerge and change over time and subclinical nuances of neurobehavior are often unrecognized. To date, only a handful of epidemiological studies examining neurodevelopment have utilized multi-pollutant models in the investigation of heavy metals and EDCs. However, these studies were successful in identifying contaminants of importance from the exposure mixtures.Summary and OutlookInvestigators are encouraged to broaden their focus to include more environmentally relevant mixtures of chemicals using advanced statistical approaches, particularly to aid in identifying potential mechanisms underlying associations.


Author(s):  
Tingting Xu ◽  
Andrew Kirkpatrick ◽  
Jody Toperzer ◽  
Marvin Steven Furches ◽  
Steven Ripp ◽  
...  

2005 ◽  
Vol 40 (4) ◽  
pp. 484-490 ◽  
Author(s):  
Keun J. Choi ◽  
Sang G. Kim ◽  
Chang W. Kim ◽  
Seung H. Kim

Abstract This study examined the effect of polyphosphate on removal of endocrine-disrupting chemicals (EDCs) such as nonylphenol and bisphenol-A by activated carbons. It was found that polyphosphate aided in the removal of nonylphenol and bisphenol- A. Polyphosphate reacted with nonylphenol, likely through dipole-dipole interaction, which then improved the nonylphenol removal. Calcium interfered with this reaction by causing competition. It was found that polyphosphate could accumulate on carbon while treating a river. The accumulated polyphosphate then aided nonylphenol removal. The extent of accumulation was dependent on the type of carbon. The accumulation occurred more extensively with the wood-based used carbon than with the coal-based used carbon due to the surface charge of the carbon. The negatively charged wood-based carbon attracted the positively charged calcium-polyphosphate complex more strongly than the uncharged coal-based carbon. The polyphosphate-coated activated carbon was also effective in nonylphenol removal. The effect was different depending on the type of carbon. Polyphosphate readily attached onto the wood-based carbon due to its high affinity for polyphosphate. The attached polyphosphate then improved the nonylphenol removal. However, the coating failed to attach polyphosphate onto the coal-based carbon. The nonylphenol removal performance of the coal-based carbon remained unchanged after the polyphosphate coating.


2019 ◽  
Vol 3 ◽  
pp. 27
Author(s):  
Bellavia A ◽  
Mínguez-Alarcón L ◽  
Ford J ◽  
Keller M ◽  
Petrozza J ◽  
...  

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