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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
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Disinfection Byproducts Bind Human Estrogen Receptor-α.
Breanne E Holmes1, Lisa Smeester1, Rebecca C Fry1
1Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Environmental Toxicology and Chemistry
|January 31, 2019
Summary
Many disinfection byproducts can weakly bind to the human estrogen receptor (ER). Even weak binding is significant when considering human exposure to mixtures in drinking water.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Water Chemistry
Background:
- Disinfection byproducts (DBPs) are common in treated drinking water and >800 are known.
- Some DBPs are linked to adverse health outcomes like cancer and infertility, but mechanisms are unclear.
- Potential disruption of the estrogen-signaling pathway by DBPs is not well understood.
Purpose of the Study:
- To evaluate the binding affinity of 21 disinfection byproducts to the human estrogen receptor (ER).
- To investigate the binding of DBP mixtures to the ER.
- To assess the potential endocrine-disrupting activity of DBPs.
Main Methods:
- In silico evaluation of binding affinity to the human ER for 21 DBPs.
- Assessment of DBP binding affinities using log median inhibitory concentration (MIC) values.
- Analysis of binary mixtures of DBPs and 4-n-nonylphenol for concentration addition.
Main Results:
- Nine of the 21 evaluated DBPs exhibited weak binding to the human ER.
- Measured binding affinities ranged from log MIC values of -3.83 to -2.19 M.
- In binary mixtures, DBPs followed concentration addition, with minimal contribution from individual weak binders.
Conclusions:
- A variety of DBP structures can bind to the human ER.
- The weak binding of DBPs to the ER is relevant for human health risk assessment, especially in mixture exposures.
- Further research is needed to understand the full impact of DBPs on the endocrine system.
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