Use of engineered <i>Escherichia coli</i> cells to detect estrogenicity in everyday consumer products

Gawrys, Michelle D.; Hartman, Izabela; Landweber, Laura F.; Wood, David

doi:10.1002/jctb.2254

Cited by 10 publications

(12 citation statements)

References 42 publications

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“…Post-prediction literature surveying estrogenic experiment data of the compounds supported our model predictions. The estrogenic activity data have been reported for benzophenone-4 ( 6 ) [30,31,32], 4-methylbenzylidene camphor ( 7 ) [33], benzophenone-1 ( 28 ) [30,31] and benzophenone-2 ( 29 ) [30,31,34,35,36]. As a result, all of these ingredients pose a concern that they may be potential endocrine-mediated health hazards.…”

Section: Discussionmentioning

confidence: 99%

Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

Hong

Rua

Sakkiah

et al. 2016

IJERPH

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Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The “active” ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions.

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Section: Discussionmentioning

confidence: 99%

Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

Hong

Rua

Sakkiah

et al. 2016

IJERPH

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“…Importantly, the temperature plays an important role in the sensitivity of biosensors, and is related to the stability of TS and the cellular demand for dTMP. Therefore, bacterial cell growth is typically carried out in 96-well plates, incubated at precisely 34°C in a controlled humidity air shaker at 150 rpm (Gawrys et al, 2009;Gierach et al, 2011). 3.…”

Section: Engineered Allosteric Bacterial Biosensormentioning

confidence: 99%

“…Notably, essential oils (e.g., Lavender Oil by Plantlife) and soaps were screened but were toxic to the bacterial cells (Gawrys et al, 2009). …”

Section: Screening Of Home Products For Estrogenic Activitymentioning

confidence: 99%

“…estradiol, T 3 , triac, tamoxifen, GC-1, diethylstilbestrol, KB-141, daidzein, DPN and genistein Escherichia coli (Gawrys et al, 2009;Hartman et al, 2009;Skretas et al, 2007;Skretas & Wood, 2005a, 2005b, 2005c Escherichia coli (Ahn et al, 2009) Microgravity and space radiation bacterial biosensors Analysis of the level of radiation exposure on human body by bacterial detection Salmonella typhimurium (Rabbow et al, 2003) Stress-responsive bacterial biosensors DNA damage by oxidative and genotoxic conditions Escherichia coli (Mitchell & Gu, 2004) …”

Section: Hormones Pharmaceuticals Endocrine Disruptorsmentioning

confidence: 99%

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Engineered Nuclear Hormone Receptor-Biosensors for Environmental Monitoring and Early Drug Discovery

Gierach¹,

Wood²

2011

Biosensors for Health, Environment and Biosecurity

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“…In particular, the binding of an appropriate ligand to the fused LBD activates a thymidylate synthase (TS) reporter enzyme, which allows the E. coli strain D1210DthyA expressing this protein to grow in media lacking thymine. This sensor is capable of differentiating agonist compounds from antagonist compounds and has shown utility in the identification and characterization of a number of compounds that bind to human and animal estrogen receptors (ERs; Gawrys et al 2009, Gierach et al 2013. More recently, this strategy has been validated for subtype-selective human TR ligands using a small library of known selective ligands (Gierach et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the roles of mutations in thyroid hormone receptor-β by a bacterial biosensor system

Shi¹,

Meng²,

Wood³

2013

Journal of Molecular Endocrinology

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Mutations in thyroid hormone receptors (TRs) often lead to metabolic and developmental disorders, but patients with these mutations are difficult to treat with existing thyromimetic drugs. In this study, we analyzed six clinically observed mutations in the ligand-binding domain of the human TRb using an engineered bacterial hormone biosensor. Six agonist compounds, including triiodothyronine (T 3 ), thyroxine (T 4 ), 3,5,3 0 -triiodothyroacetic acid (Triac), GC-1, KB-141, and CO-23, and the antagonist NH-3 were examined for their ability to bind to each of the TRb mutants. The results indicate that some mutations lead to the loss of ability to bind to native ligands, ranging from several fold to several hundred fold, while other mutations completely abolish the ability to bind to any ligand. Notably, the effect of each ligand on each TRb mutant in this bacterial system is highly dependent on both the mutation and the ligand; some ligands were bound well by a wide variety of mutants, while other ligands lost their affinity for all but the WT receptor. This study demonstrates the ability of our bacterial system to differentiate agonist compounds from antagonist compounds and shows that one of the TRb mutations leads to an unexpected increase in antagonist ability relative to other mutations. These results indicate that this bacterial sensor can be used to rapidly determine ligand-binding ability and character for clinically relevant TRb mutants. Key Words" thyroid hormone receptor " ligand-binding assay " hormone receptor mutations " engineered biosensor

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Use of engineered Escherichia coli cells to detect estrogenicity in everyday consumer products

Cited by 10 publications

References 42 publications

Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

Engineered Nuclear Hormone Receptor-Biosensors for Environmental Monitoring and Early Drug Discovery

Analysis of the roles of mutations in thyroid hormone receptor-β by a bacterial biosensor system

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