ACEA Biosciences develops novel assay for the rapid and facile detection of agonists and antagonists of key endocrine receptors.
Endocrine-disrupting chemicals (EDCs) are substances that interfere with the ability of endogenous hormones to regulate homeostasis via their cognate nuclear receptors. By either mimicking ligands (agonists) or inhibiting ligand binding activity (antagonists), EDCs produce adverse reproductive, neurological, proliferative, and immunological disorders. EDC exposure can occur directly, through the use of consumer products which contain these compounds. Alternatively, because many constituents of consumer products, pesticides, and pharmaceuticals biodegrade poorly, they accumulate in the environment and can subsequently cause EDC exposure through dermal, inhalation, embryonic, and oral routes in both humans and wildlife. EDC-laden wastewater causing intersex characteristics in fish, and the correlation between breast cancer and bisphenol A are just two examples which highlight the severity of the EDC problem and the necessity of developing more efficient means of identifying these compounds prior to them being included in consumer products or being used openly in the environment.
The estrogen, androgen, and thyroid hormone systems are primary regulators of a broad array of critical physiological functions and are targets of numerous EDCs. The in vitro assays that have historically been employed to detect EDCs which interact with the estrogen receptor (ER), androgen receptor (AR), or thyroid hormone receptor (TR) only generate end point data – representing mere snapshots in the dynamic continuum of a cell’s response to a treatment/exposure. Working with such a limited data set can lead to spurious conclusions and poor predictivity of how a compound will behave in vivo.
Today ACEA Biosciences announced the development of a novel approach for detecting and characterizing EDCs in a wide variety of sample types using a panel of cell lines and their xCELLigence Real-Time Cell Analysis instruments. This methodology was summarized in an application note that can be viewed here. “This cell-based assay enables quantitative, noninvasive, and continuous monitoring of cellular responses to chemicals of interest. Moreover, it provides a substantial improvement in data quality and quantity all while being automated and having a very simple workflow,” said lead scientist Dr. Can Jin. Three mammalian cell lines, each of which is responsive to modulators of ER, AR, or TR, were analyzed for their real-time responses to reference agonists and antagonists. The unique specificity and sensitivity of each cell line to the different reference compounds were then used as standards that data from “unknown” compounds could be compared to. In addition to enabling the rapid and facile identification of EDC activity in previously uncharacterized compounds, the specific identity of the endocrine receptor that is being agonized or antagonized can be elucidated. “Employing multiple cell lines in this xCELLigence assay provides a multifaceted view of a potential EDC, thereby improving the predictive value of the assay,” said research scientist Dr. Diana Guimet. “This methodology can be expanded to study any type of nuclear receptor activation, given that the downstream effects involve changes in cell proliferation, morphology, and/or cell attachment quality.”
ACEA’s xCELLigence® Real Time Cell Analysis (RTCA) instruments utilize gold microelectrodes embedded in the bottom of microtiter wells to non-invasively monitor the status of adherent cells using the principle of cellular impedance. In short, cells act as insulators – impeding the flow of an alternating microampere electric current between electrodes. This impedance signal is measured automatically, at an interval defined by the user (e.g. every 10 seconds, once per hour, etc.), and provides an extremely sensitive readout of cell number, cell size/shape, and cell-substrate attachment strength.
About ACEA Biosciences
Founded in 2002, ACEA Biosciences is a pioneer in the development and commercialization of high performance, cutting edge cell analysis platforms for life science research. ACEA’s xCELLigence® impedance-based, label-free, real-time cell analysis instruments and NovoCyte® flow cytometer are used in pre-clinical drug discovery and development, toxicology, safety pharmacology, and basic academic research. More than 2,000 instruments have been placed globally, leading to >1,250 peer reviewed publications.
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For further information please contact:
ACEA Biosciences, Inc.
Dr. Jeff Xue
Phone: +1 858 724 0928 x 3075