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Estrogenic activity of multicyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) in vitro assays
Citation:
Kolanczyk, Rick, J. Denny, B. Sheedy, P. Schmieder, AND M. Tapper. Estrogenic activity of multicyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) in vitro assays. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 207:43-51, (2019). https://doi.org/10.1016/j.aquatox.2018.11.023
Impact/Purpose:
This first report of bridging multicyclic aromatic hydrocarbons in fish demonstrates binding for a series of chemicals normally not thought of as having an affinity for the ER and further illustrates the variety of chemical structures capable of binding to the ER. In fact, 3PE shows a high binding affinity for rtER (RBA=3.0%) and high potency in the Vtg mRNA expression liver slice assay, comparable to higher affinity steroids like E1, E3, and αE2. We were able to expand the ERES model decision tree for chemical prioritization while incorporating multicyclic aromatic hydrocarbons.
Description:
A representative group of multicyclic aromatic hydrocarbons (MAHC) which can be further classified as bridged-ring (bridged-MAHC) or fused-ring (fused-MAHC) were examined for their ability to interact with the estrogen receptor of rainbow trout (rtER) in a hepatic cytosolic estrogen receptor competitive binding assay (cyto rtERáâ) and the vitellogenin (Vtg) mRNA gene activation liver slice assay. All five fused-MAHCs; naphthalene (NAFT), fluorene (FE), Fluoranthene (FAT), pyrene (PY), and 9,10-dihydroanthracene (DAC) had no estrogenic activity in the in vitro assays used. Five of the eight bridged-MAHCs; triphenylethylene (3PE), o-terphenyl (OTP), triphenylmethane (TPM), 1,1-diphenylethylene (DPE), and cis-stilbene (CSB) were estrogenic in these assays. The additional three bridged-MAHC’s; trans-stilbene (TSB), tetraphenylethylene (4PE), and 4,4-di-tertbutylphenyl (DtBB) were determined to be non-binders due to isomeric configuration, solubility limitation, and possible steric hinderance. It is possible that the bridged-MAHCs bind to the rtER through a proposed aromatic-aromatic stacking (ð-ð interaction) facilitated by perpendicular ring orientation achieved through free rotation of the bridged rings. The fused-ring structures are locked in a planar configuration which doesn’t allow for rotation of rings perpendicular to one another. This first report of the rtER-binding of bridged-MAHCs in fish demonstrates binding for a class of chemicals normally not thought of as having an affinity for the estrogen receptor and further supports the versatility or promiscuity of ER ligand selectivity.
URLs/Downloads:
DOI: Estrogenic activity of multicyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) in vitro assays