In vitro profiling of toxicity and endocrine disrupting effects of bisphenol analogues by employing MCF‐7 cells and two‐hybrid yeast bioassay

Abstract

The potentially adverse health implications of bisphenol A (BPA) have led to increasing use of alternative bisphenols (BPs). However, little is known about the toxicity of alternative BPs. In this study, the cytotoxicity, genotoxicity, intracellular ROS formation, and Ca fluctuation effects of BPs on MCF-7 cells were evaluated. At the same time, the estrogenic and thyroidal hormone effect potentials of six BPs were also evaluated using two-hybrid yeast bioassay. The results showed that most BPs at 0.01-1 μM significantly increased cell viability in MCF-7 cells and at higher exposure concentrations of 25-100 μM, they caused a significant decrease of cell viability. At the same time, these BPs also at 25-100 μM significantly increased LDH release of MCF-7 cells. In addition, several BPs at 10-50 μM resulted in a significantly concentration-depended increase in DNA-damaging effect on MCF-7 cells and elevated ROS production. Most BPs at 0.0001-10 μM significantly increased intracellular Ca level. These results showed that bisphenol AF (BPAF) and thiodiphenol (TDP) exerted cell biological effect, estrogenic, and thyroidal effect potentials greater than those of BPA. The cytotoxicity and endocrine disrupting effects of other BPs are similar to or slightly lower than those of BPA. Therefore, as potential alternatives to BPA, endocrine disrupting effects and potential health harm of alternative BPs to human can also not be ignored. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 278-289, 2017.

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

“…Although the chemical structures of BPA and its analogues are similar, HCA demonstrated differential adverse effects of 4 bisphenols on multiple molecular and cellular events, suggesting that different mechanisms may promote cytotoxicity. Similar findings were reported in previous in vitro studies, in which BPAF and TBBPA showed higher endocrine modulating potentials in human MCF7 breast cancer cells and Leydig cells, respectively, as compared with BPA (Lei et al, 2016;Roelofs et al, 2015). BPS showed similar inhibitory effects with BPA on testosterone secretion in human fetal testes and induced more sensitive responses in mice testes (Eladak et al, 2015).…”

Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo

“…In addition to perturbing the ER pathway, BPAF and BPC have been reported to interact with other endocrine targets (Delfosse et al, 2014;Grimaldi et al, 2019;Lei et al, 2017;Wang et al, 2014). The increasing and widespread use of these bisphenol analogues and their ability to interact with endocrine molecular targets at lower concentrations than BPA pose a serious concern associated with potential health risks for humans and wildlife.…”

Use of a Mouse Model of Experimentally Induced Endometriosis to Evaluate and Compare the Effects of Bisphenol A and Bisphenol AF Exposure

“…2016; Rachoń 2015). The bisphenols are EDCs known to act through the estrogen receptors (ERs) to regulate downstream signaling and gene expression responses (Lei et al. 2017; Li et al.…”