Cheryl Walker, Ph.D.
Texas A&M University
NIEHS Grants RCES018789, R01ES023206
Researchers funded by the NIEHS developed a high-throughput microscopy approach for examining how bisphenol A (BPA) and similar chemicals affect alpha and beta estrogen receptors, which are the primary targets of endocrine disrupting chemicals such as BPA. Applying this approach on a large scale could offer a faster, more cost-effective way to determine if BPA alternatives are safe.
Because of concerns surrounding BPA’s possible effects on development, reproduction, and metabolism, BPA analogs have been developed and are replacing BPA. Since many of these analogs have not been thoroughly analyzed, it isn’t known if they might also have endocrine disrupting activity. The researchers developed a series of assays for use with high-throughput microscopy that can cost-effectively reveal the mechanisms of a chemical’s endocrine disrupting activity on a cell-by-cell basis.
Using the new assays, the investigators studied BPA and 18 under-studied BPA analogs. They found that BPA and nearly all the analogs bound to alpha and/or beta estrogen receptors. But even at the highest dose tested across multiple assays, some of the analogs were inactive or had very low activity in other functional endpoint assays, indicating that receptor binding alone should not be used to classify activity. The authors note that the assays allow classification and identification of a chemical’s endocrine disrupting activity, and are highly complementary with the assays used in the U.S. Environmental Protection Agency Toxcast program
Citation: Stossi F, Bolt MJ, Ashcroft FJ, Lamerdin JE, Melnick JS, Powell RT, Dandekar RD, Mancini MG, Walker CL, Westwick JK, Mancini MA. 2014. Defining Estrogenic Mechanisms of Bisphenol A Analogs through High Throughput Microscopy-Based Contextual Assays. Chem Biol; doi:10.1016/j.chembiol.2014.03.013.