Characterization of Estrogenic and Androgenic Activities for Bisphenol A-like Chemicals (BPs): In Vitro Estrogen and Androgen Receptors Transcriptional Activation, Gene Regulation, and Binding Profiles

Toxicological Sciences - Tập 172 Số 1 - Trang 23-37 - 2019
Katherine E. Pelch1, Yin Li2, L. Perera3, Kristina A. Thayer1, Kenneth S. Korach2
1National Toxicology Program
2Reproductive and Developmental Biology Laboratory
3Genome Integrity and Structure Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Tóm tắt

Abstract

Bisphenol A (BPA) is a high production volume chemical widely used in plastics, food packaging, and many other products. It is well known that endocrine-disrupting chemicals might be harmful to human health due to interference with normal hormone actions. Recent studies report widespread usage and exposure to many BPA-like chemicals (BPs) that are structurally or functionally similar to BPA. However, the biological actions and toxicity of those BPs are still relatively unknown. To address this data gap, we used in vitro cell models to evaluate the ability of 22 BPs to induce or inhibit estrogenic and androgenic activity. BPA, Bisphenol AF (BPAF), bisphenol Z (BPZ), bisphenol C (BPC), tetramethyl bisphenol A (TMBPA), bisphenol S (BPS), bisphenol E (BPE), 4,4-bisphenol F (4,4-BPF), bisphenol AP (BPAP), bisphenol B (BPB), tetrachlorobisphenol A (TCBPA), and benzylparaben (PHBB) induced estrogen receptor (ER)α and/or ERβ-mediated activity. With the exception of BPS, TCBPA, and PHBB, these same BPs were also androgen receptor (AR) antagonists. Only 3 BPs were found to be ER antagonists. Bisphenol P (BPP) selectively inhibited ERβ-mediated activity and 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE) and 2,4-bisphenol S (2,4-BPS) selectively inhibited ERα-mediated activity. None of the BPs induced AR-mediated activity. In addition, we identify that the BPs can bind to ER or AR with varying degrees by a molecular modeling analysis. Taken together, these findings help us to understand the molecular mechanism of BPs and further consideration of their usage in consumer products.

Từ khóa


Tài liệu tham khảo

Acconcia, 2015, Molecular mechanisms of action of BPA, Dose Response, 13, 1559325815610582., 10.1177/1559325815610582

American Chemistry Council, 2013

Becerra, 2013, Interferences in the direct quantification of bisphenol S in paper by means of thermochemolysis, J. Chromatogr. A, 1275, 70, 10.1016/j.chroma.2012.12.034

Bermudez, 2010, Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol AF in an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc), Toxicol. Sci, 116, 477, 10.1093/toxsci/kfq156

Bhattacharjee, 2013, Combinatorial control of gene expression, Biomed Res. Int., 2013, 407263., 10.1155/2013/407263

Bjornsdotter, 2017, Bisphenol A alternatives in thermal paper from the Netherlands, Spain, Sweden and Norway. Screening and potential toxicity, Sci. Total Environ., 601–602, 210, 10.1016/j.scitotenv.2017.05.171

Burns, 2012, Estrogen receptors and human disease: An update, Arch. Toxicol., 86, 1491, 10.1007/s00204-012-0868-5

Cacho, 2012, Stir bar sorptive extraction coupled to gas chromatography-mass spectrometry for the determination of bisphenols in canned beverages and filling liquids of canned vegetables, J. Chromatogr. A, 1247, 146, 10.1016/j.chroma.2012.05.064

Charisiadis, 2018, Possible obesogenic effects of bisphenols accumulation in the human brain, Sci. Rep., 8, 8186., 10.1038/s41598-018-26498-y

Cobellis, 2009, Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women, Biomed. Chromatogr., 23, 1186, 10.1002/bmc.1241

Cobellis, 2010, Relationship between endometriosis and exposure to BPA and BPB, Giornale Italiano di Ostetricia e Ginecologia, 32, 44

Conley, 2016, A demonstration of the uncertainty in predicting the estrogenic activity of individual chemicals and mixtures from an in vitro estrogen receptor transcriptional activation assay (T47D-KBluc) to the in vivo uterotrophic assay using oral exposure, Toxicol. Sci, 153, 382, 10.1093/toxsci/kfw134

Cunha, 2010, Quantification of free and total bisphenol A and bisphenol B in human urine by dispersive liquid-liquid microextraction (DLLME) and heart-cutting multidimensional gas chromatography-mass spectrometry (MD-GC/MS), Talanta, 83, 117, 10.1016/j.talanta.2010.08.048

Delfosse, 2012, Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes, Proc. Natl. Acad. Sci. U.S.A., 109, 14930, 10.1073/pnas.1203574109

Deliperi, 2003, Effect of different polymerization methods on composite microleakage, Am. J. Dent, 16, 73A

Deroo, 2006, Estrogen receptors and human disease, J. Clin. Invest., 116, 561, 10.1172/JCI27987

Eckardt, 2017, Bisphenol A and alternatives in thermal paper receipts—A German market analysis from 2015 to 2017, Chemosphere, 186, 1016, 10.1016/j.chemosphere.2017.08.037

Ferguson, 2018, Environmental phenol associations with ultrasound and delivery measures of fetal growth, Environ. Int., 112, 243, 10.1016/j.envint.2017.12.011

Fic, 2014, Estrogenic and androgenic activities of TBBA and TBMEPH, metabolites of novel brominated flame retardants, and selected bisphenols, using the XenoScreen XL YES/YAS assay, Chemosphere, 112, 362, 10.1016/j.chemosphere.2014.04.080

Gaido, 2000, Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: Structure-activity studies, Mol. Pharmacol., 58, 852, 10.1124/mol.58.4.852

Goldinger, 2015, Endocrine activity of alternatives to BPA found in thermal paper in Switzerland, Regul. Toxicol. Pharmacol., 71, 453, 10.1016/j.yrtph.2015.01.002

Gramec Skledar, 2015, Differences in the glucuronidation of bisphenols F and S between two homologous human UGT enzymes, 1A9 and 1A10, Xenobiotica, 45, 511, 10.3109/00498254.2014.999140

Grignard, 2012, Weak estrogenic transcriptional activities of bisphenol A and bisphenol S, Toxicol. In Vitro, 26, 727, 10.1016/j.tiv.2012.03.013

Grimaldi, 2019, Functional profiling of bisphenols for nuclear receptors, Toxicology, 420, 39, 10.1016/j.tox.2019.04.003

Hsieh, 2015, A data analysis pipeline accounting for artifacts in Tox21 quantitative high-throughput screening assays, J. Biomol. Screen., 20, 887, 10.1177/1087057115581317

Kang, 2014, Estrogenic potency of bisphenol S, polyethersulfone and their metabolites generated by the rat liver S9 fractions on a MVLN cell using a luciferase reporter gene assay, Reprod. Biol. Endocrinol., 12, 102., 10.1186/1477-7827-12-102

Karrer, 2018, Physiologically based pharmacokinetic (PBPK) modeling of the bisphenols BPA, BPS, BPF, and BPAF with new experimental metabolic parameters: Comparing the pharmacokinetic behavior of BPA with its substitutes, Environ. Health Perspect., 126, 077002., 10.1289/EHP2739

Kataria, 2017, Exposure to bisphenols and phthalates and association with oxidant stress, insulin resistance, and endothelial dysfunction in children, Pediatr. Res., 81, 857, 10.1038/pr.2017.16

Kelley, 2015, POSIT: Flexible shape-guided docking for pose prediction, J. Chem. Inf. Model., 55, 1771, 10.1021/acs.jcim.5b00142

Kitamura, 2005, Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds, Toxicol. Sci, 84, 249, 10.1093/toxsci/kfi074

Kitamura, 2007, Thyroid hormonal and estrogenic activity of OH-PCB and OH-PBDE in cell culture, Organohalogen Compd, 69, 213/1

Kobayashi, 2006, Stereo structure-controlled and electronic structure-controlled estrogen-like chemicals to design and develop non-estrogenic bisphenol A analogs based on chemical hardness concept, Chem. Pharm. Bull., 54, 1633, 10.1248/cpb.54.1633

Kolsek, 2015, Screening of bisphenol A, triclosan and paraben analogues as modulators of the glucocorticoid and androgen receptor activities, Toxicol. In Vitro, 29, 8, 10.1016/j.tiv.2014.08.009

Kuruto-Niwa, 2005, Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system, Environ. Toxicol. Pharmacol., 19, 121, 10.1016/j.etap.2004.05.009

Lehmler, 2018, Exposure to bisphenol A, bisphenol F, and bisphenol S in U.S. adults and children: The National Health and Nutrition Examination Survey 2013–2014, ACS Omega, 3, 6523, 10.1021/acsomega.8b00824

Li, 2012, Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor alpha and beta in vitro, Environ. Health Perspect., 120, 1029, 10.1289/ehp.1104689

Li, 2013, Endocrine-disrupting chemicals (EDCs): In vitro mechanism of estrogenic activation and differential effects on ER target genes, Environ. Health Perspect., 121, 459, 10.1289/ehp.1205951

Li, 2018, Differential in vitro biological action, coregulator interactions, and molecular dynamic analysis of bisphenol A (BPA), BPAF, and BPS ligand-ERalpha complexes, Environ. Health Perspect., 126, 017012., 10.1289/EHP2505

Liao, 2013, Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure, J. Agric. Food Chem., 61, 4655, 10.1021/jf400445n

Liao, 2014, A survey of alkylphenols, bisphenols, and triclosan in personal care products from China and the United States, Arch. Environ. Contam. Toxicol., 67, 50, 10.1007/s00244-014-0016-8

Liao, 2012, Bisphenol S in urine from the United States and seven Asian countries: Occurrence and human exposures, Environ. Sci. Technol., 46, 6860, 10.1021/es301334j

Liao, 2012, Occurrence of eight bisphenol analogues in indoor dust from the United States and several Asian countries: Implications for human exposure, Environ. Sci. Technol., 46, 9138, 10.1021/es302004w

Liao, 2012, Bisphenol S, a new bisphenol analogue, in paper products and currency bills and its association with bisphenol a residues, Environ. Sci. Technol., 46, 6515, 10.1021/es300876n

Liu, 2017, Bisphenol A substitutes and obesity in US adults: Analysis of a population-based, cross-sectional study, Lancet Planet. Health, 1, e114, 10.1016/S2542-5196(17)30049-9

Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262

Matsushima, 2010, Bisphenol AF is a full agonist for the estrogen receptor ERalpha but a highly specific antagonist for ERbeta, Environ. Health Perspect., 118, 1267, 10.1289/ehp.0901819

Mendum, 2011, Concentration of bisphenol A in thermal paper, Green Chem. Lett. Rev., 4, 81, 10.1080/17518253.2010.502908

Molina-Molina, 2013, In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors, Toxicol. Appl. Pharmacol., 272, 127, 10.1016/j.taap.2013.05.015

Mueller, 2003, Molecular determinants of the stereoselectivity of agonist activity of estrogen receptors (ER) alpha and beta, J. Biol. Chem., 278, 12255, 10.1074/jbc.M203578200

Mustieles, 2018, Maternal and paternal preconception exposure to bisphenols and size at birth, Hum. Reprod, 33, 1528, 10.1093/humrep/dey234

NICCA USA Inc, 1996

Nishigori, 2012, Highly potent binding and inverse agonist activity of bisphenol A derivatives for retinoid-related orphan nuclear receptor RORgamma, Toxicol. Lett., 212, 205, 10.1016/j.toxlet.2012.05.020

Pelch, 2019, A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives, Toxicology, 424, 152235, 10.1016/j.tox.2019.06.006

Pelch, 2017

Prins, 2014, Bisphenol A promotes human prostate stem-progenitor cell self-renewal and increases in vivo carcinogenesis in human prostate epithelium, Endocrinology, 155, 805, 10.1210/en.2013-1955

Rochester, 2013, Bisphenol A and human health: A review of the literature, Reprod. Toxicol, 42, 132, 10.1016/j.reprotox.2013.08.008

Rochester, 2018, Prenatal exposure to bisphenol A and hyperactivity in children: A systematic review and meta-analysis, Environ. Int., 114, 343, 10.1016/j.envint.2017.12.028

Roelofs, 2015, Structural bisphenol analogues differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor, Toxicology, 329, 10, 10.1016/j.tox.2015.01.003

Rosenmai, 2014, Are structural analogues to bisphenol a safe alternatives?, Toxicol. Sci, 139, 35, 10.1093/toxsci/kfu030

Ruan, 2015, Evaluation of the in vitro estrogenicity of emerging bisphenol analogs and their respective estrogenic contributions in municipal sewage sludge in China, Chemosphere, 124, 150, 10.1016/j.chemosphere.2014.12.017

Song, 2014, Assessing developmental toxicity and estrogenic activity of halogenated bisphenol A on zebrafish (Danio rerio), Chemosphere, 112, 275, 10.1016/j.chemosphere.2014.04.084

Tan, 2015, Androgen receptor: Structure, role in prostate cancer and drug discovery, Acta Pharmacol. Sin., 36, 3, 10.1038/aps.2014.18

Teng, 2013, Bisphenol A affects androgen receptor function via multiple mechanisms, Chem. Biol. Interact., 203, 556, 10.1016/j.cbi.2013.03.013

Terasaki, 2007, Occurrence and estrogenicity of phenolics in paper-recycling process water: Pollutants originating from thermal paper in waste paper, Environ. Toxicol. Chem., 26, 2356, 10.1897/06-642R.1

Thayer, 2016, Bisphenols: More unnecessary surprises, Endocr. Disruptors, 4, e1131032., 10.1080/23273747.2015.1131032

Tice, 2013, Improving the human hazard characterization of chemicals: A Tox21 update, Environ. Health Perspect., 121, 756, 10.1289/ehp.1205784

US EPA, 2014

US EPA, 2016

Vandenberg, 2013, Low dose effects of bisphenol A, Endocr. Disruptors, 1, e26490., 10.4161/endo.26490

Vandenberg, 2007, Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland, Endocrinology, 148, 116, 10.1210/en.2006-0561

Wan, 2018, Relationship between maternal exposure to bisphenol S and pregnancy duration, Environ. Pollut, 238, 717, 10.1016/j.envpol.2018.03.057

Wang, 2014, Extending an in vitro panel for estrogenicity testing: The added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis, Toxicol. Sci., 141, 78, 10.1093/toxsci/kfu103

Wilson, 2002, A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists, Toxicol. Sci., 66, 69, 10.1093/toxsci/66.1.69

Ye, 2015, Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of U.S. adults during 2000–2014, Environ. Sci. Technol, 49, 11834, 10.1021/acs.est.5b02135

Zhang, 2009, Jointed estrogenic activities of bisphenol A and three of its analogs, Huan Jing Ke Xue, 30, 260

Zhang, 2019, Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models, Environ. Int., 123, 325, 10.1016/j.envint.2018.11.076

Zhou, 2013, Measurement of phenolic environmental estrogens in human urine samples by HPLC-MS/MS and primary discussion the possible linkage with uterine leiomyoma, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 938, 80, 10.1016/j.jchromb.2013.08.032

Zhou, 2014, Automated on-line column-switching high performance liquid chromatography isotope dilution tandem mass spectrometry method for the quantification of bisphenol A, bisphenol F, bisphenol S, and 11 other phenols in urine, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci, 944, 152, 10.1016/j.jchromb.2013.11.009