Abstract

Bisphenol A and its substitutions are commonly used to manufacture epoxy resins, plastic materials and different kinds of daily necessities. In this process, a large number of bisphenol analogues (BPs) are continuously released directly/indirectly into the environment. Through the chain of environment–feed–farmed-animals–livestock and poultry products, BPs present the low concentration but chronic exposure for surroundings and environment. In addition, BPs have been revealed by extensive studies as emerging endocrine disruptors, whose effects on androgens/glucocorticoids have rarely been mentioned in previous reports. The (anta-) agonist/antagonist properties of 18 classic BPs were investigated in vitro: We assessed the cytotoxicity and examined the luciferase induction values of BPs in MDA-kb2 cells, incubated single or co-incubated with dihydrotestosterone (DHT), dexamethasone, flutamide and RU486 for 24 h. From the concentration of 10−10 to 10−5 M, BPs had negligible cytotoxicity for MDA-kb2 cells, except for 4,4′-(9-Fluorenylidene)diphenol with the IC50 1.32 μM. All 18 BPs had the response to androgen/glucocorticoid receptors (AR/GR). BPs at nanomolar and trace concentrations are agonists, while BPs at micromolar and higher concentrations are antagonists. Molecular docking showed that BPs interact with AR/GR through hydrophobic bonds, hydrogen bonds, T-type π-stacking and water-bridge. These experimental data demonstrate the universality of the endocrine-disrupting effects of BPs and suggest the urgency of paying attention to the usages of BPs.

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