Xenoestrogens Modulate Vascular Endothelial Growth Factor Secretion in Breast Cancer Cells Through an Estrogen Receptor-Dependent Mechanism

Total Page:16

File Type:pdf, Size:1020Kb

Xenoestrogens Modulate Vascular Endothelial Growth Factor Secretion in Breast Cancer Cells Through an Estrogen Receptor-Dependent Mechanism 399 Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism He´le`ne Buteau-Lozano1,2, Guillaume Velasco1,2, Monique Cristofari1,2, Patrick Balaguer3 and Martine Perrot-Applanat1,2 1INSERM, U553, He´mostase, Endothe´lium et Angioge´ne`se, Hoˆpital Saint Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France 2IFR105 Universite´ Paris 7, 75000 Paris, France 3INSERM, U824, Signalisation hormonale, Environnement et Cancer, 34098 Montpellier, France (Correspondence should be addressed to M Perrot-Applanat; Email: [email protected]) Abstract Environmental chemicals may affect human health by disrupting 182 780. VEGF increase was not observed in ERa-negative endocrine function. Their possible role in the mammary gland MDA-MB-231 cells. Most substances increased VEGF tran- and breast tumors is still unknown. Previous studies have script levels in MELN cells. In contrast, g-hexachlorocyclohex- demonstrated that vascular endothelial growth factor (VEGF), a ane, vinclozolin, and the phthalates (mono-n-butyl ester key factor in angiogenesis and tumor progression, is an estrogen- phthalic acid, di-isononyle phthalate, and di-isodecyle phtha- regulated gene. We analyzed whether VEGF expression is late) were ineffective on both VEGF secretion and estrogenic regulated by differentxenoestrogens in several breast cancercells, luciferase induction in these cell lines. Specific kinase inhibitors MELN (derived from MCF-7) and MELP (derived from MDA- PD98059, SB203580, or LY294002 suppressed the xenoestro- MB-231) and stablyexpressing estrogen receptor a (ERa); these gen-induced VEGF response, suggesting activation of MEK, cell lines stably express estrogen response element (b-globin)- p38 kinase, and phosphatidylinositol-3-kinase pathways. Our luciferase. Genistein, bisphenol A (BPA), 4-(tert-octyl)phenol in vitro results show for the first time that genistein and (OP), dieldrin, and several phthalates, including benzyl butyl xenoestrogens (BPA, OP, dieldrin, BBP, and DEHP at high phthalate (BBP) and di-ethyl-2-hexyle phthalate (DEHP), were concentrations) up-regulate VEGF expression in MELN cells first shown to be estrogenic. These compounds induced a dose- by an ER-dependent mechanism. Since VEGF increases dependent increase of VEGF secretion in MELN and MCF-7 capillary permeability and breast tumor angiogenesis in vivo, cells; maximal effect was observed at 1–10 mMnon-cytotoxic the physiological relevance of these findings is discussed. concentrations and was inhibited by the antiestrogen ICI Journal of Endocrinology (2008) 196, 399–412 Introduction than endogenous estrogens when tested in biological assays, they are cause of concern due to their persistence in the environment, Over the past 20 years, a great deal of attention has focused on the resistance to chemical or enzymatic degradation, and sequestra- impact of endocrine disruptors released in the environment on tion and storage in the adipose tissue. Whether it can be implied animal and human health. A large number of these environ- that these substances in human female reproductive diseases mental pollutants, including alkylphenol compounds, poly- (precocious puberty and endometriosis, Te i l m a n n et al.2002)or chlorinated biphenyls (PCBs), polychlorinated dibenzodioxins, in steroid hormone-dependent cancers (breast, prostate) are a organochlorine pesticides, and bisphenol A (BPA), have been leading cause of mortality and morbidity in industrialized shown or suspected to disrupt endocrine functions in animals. countries, is still under debate (Sasco 2001, Birnbaum & Fenton Generally, endocrine disruptors have estrogenic activity 2003, Mitra et al. 2004, Sharpe & Irvine 2004, Safe 2005). (so-called xenoestrogens including pesticides, bisphenols and Development of the mammary gland and breast cancer in alkylphenols, some PCBs, and phthalates; Colburn 1995, Jobling women depends on diverse factors including exposure to et al. 1995, Soto et al.1995, Sonnenschein & Soto 1998, estrogens ( Jordan & Murphy 1990). Estrogens regulate cell Andersen et al. 1999), anti-androgenic activity (some pesticides; function through tissue-dependent specific intracellular Colburn 1995, Kelce et al. 1997), or disrupt thyroid function receptors (estrogen receptor, ER), acting as ligand-activated (PCBs, perchlorate, and some pesticides) (Koopman-Esseboom transcription factors. Activated ERs regulate the expression of et al. 1994). Although xenoestrogens are generally less potent many genes via direct interaction with an estrogen response Journal of Endocrinology (2008) 196, 399–412 DOI: 10.1677/JOE-07-0198 0022–0795/08/0196–399 q 2008 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org Downloaded from Bioscientifica.com at 10/01/2021 05:46:13AM via free access 400 H BUTEAU-LOZANO and others . VEGF expression by xenoestrogens in breast cells element (ERE) sequence located in the promoter or via induced by E2 in the uterus, vagina, and pituitary (Cullinan-Bove interaction with other transcription factors, such as members & Koos 1993, Shifren et al.1996, Bausero et al. 1998, Kazi et al. of activator protein-1 (AP-1), signal transducer and activator of 2005) and in rodent and primate models of mammary cancer transcription (STATs), nuclear factor-kappa B (NF-kB), and (Nakamura et al.1996, Dabrosin et al.2003). Interestingly, the specificity protein (SP-1) families (Stein & Yang 1995, Paech xenoestrogen BPA also increases VEGF expression in the uterus et al.1997). Selective effects of estrogens may be modulated by (Long et al.2001). However, whether the expression of VEGF, the receptor subtype (ERa or ERb), the relative expression of which is a key factor in tumor angiogenesis, is modulated by each receptor in a target tissue, and the promoter context of xenoestrogens in breast cancer is not known. Therefore, we estrogen-regulated genes (Carson-Jurica et al. 1990, Kuiper et al. hypothesized that xenoestrogens could modulate VEGF 1997, Paech et al.1997). The transcriptional modulation arises expression in estrogen-dependent breast cancer cells. from an interplay of interactions between co-activators and Inthepresentstudy,we tested several known and potential ER co-repressors that determine the specificityof hormone action in agonists (xenoestrogens) for their ability to induce VEGF the different tissues, a feature particularly highlighted by the expression in different breast epithelial cells. We used several puzzling pharmacology of selective ER modulators (SERMs), cellular models: i) MCF-7 cells; ii) MELN derived from MCF-7 acting as receptor agonist or antagonist depending on the target cells (Balaguer et al. 2001), which express endogenous ERa;and organ. Whether xenoestrogens, which can accumulate in iii) MELP derived from MDA-MB-231 cells, which stably adipose tissue, may play a role in the incidence or progression express ERa. Both MELN and MELP express ERE-coupled of breast tumors, is largely unknown. A few epidemiological luciferase gene, allowing us to combine the analysis of studies have reported a correlation between exposure to some endogenous VEGF expression and the induction of the ERE xenobiotics and increased incidence of tumors, including breast reporter gene by different compounds in the same cells and cancers (Hoyer et al. 1998, Mills 1998, Sasco 2001, Hope- between cells. We analyzed the effects of the phytoestrogen nhayn-Rich et al. 2002, Birnbaum & Fenton 2003, Mitra et al. genistein; BPA; 4-(tert-octyl)phenol (OP); several pesticides 2004). Prenatal exposure to endocrine disruptors, including including dieldrin, g-hexachlorocyclohexane (gHCH), vinclo- BPA, atrazine, and 2,3,7,8-tetrachlorodibenzo-p-dioxin zolin, and the herbicide atrazine; and several phthalates including (TCDD), has been shown to alter the development of the benzyl butyl phthalate (BBP), mono-n-butyl ester phthalic acid rodent mammary gland, and the susceptibility to further (MBuP), di-ethyl-2-hexyle phthalate (DEHP), di-isononyle carcinogenic exposure in adulthood (Brown et al. 1998, Markey phthalate (DINP), and di-isodecyle phthalate (DIDP). We et al.2001, Birnbaum & Fenton 2003, Fukamachi et al.2004). analyzed some of the mechanisms of VEGF regulation, such as The complexity of xenoestrogen action in vitro, and in several ER-dependent activation pathway and/or activation of kinases. physiopathological conditions, has not been well understood, especially due to the limited use and knowledge of estrogen- responsive genes. In vitro investigations of the molecular Materials and Methods mechanism of xenoestrogen effects have been focused on the proliferation test of ERa-expressing MCF-7 cells, binding Hormones and chemicals assays with ERs (a and b), reporter gene assays using ERE (Soto et al.1995, Kuiper et al.1997, Andersen et al.1999, Legler et al. E2, genistein (Gen), BPA (purity 99%), OP (purity 97%), 1999, Balaguer et al.2001, Diel et al.2002, Olsen et al.2003), or a lindane (1,2,3,4,5,6 gHCH, purity 97%), dieldrin (purity few estrogen target gene promoters (Hall & Korach 2002). 94%), vinclozolin (VIN, purity 99.6%), and atrazine (ATZ, Recently,a DNA microarray was also developed to evaluate the purity 99.2%) were purchased from Sigma or Sigma–Aldrich estrogenic activity of industrial chemicals (Terasaka et al.2004). (GmbH, D-30918). MBuP (purity 98%) was purchased from The identification of estrogen target genes is clearly needed to Interchim (Tokyo Chemical
Recommended publications
  • Is an Activator of the Human Estrogen Receptor Alpha
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Newcastle University E-Prints 1 The ionic liquid 1-octyl-3-methylimidazolium (M8OI) is an activator of the human estrogen receptor alpha Alistair C. Leitch1, Anne F. Lakey1, William E. Hotham1, Loranne Agius1, George E.N. Kass2, Peter G. Blain1, Matthew C. Wright1,* 1Institute Cellular Medicine, Health Protection Research Unit, Level 4 Leech, Newcastle University, Newcastle Upon Tyne, United Kingdom NE24HH. 2European Food Safety Authority, Via Carlo Magno 1A, 43126 Parma, Italy. *Corresponding author. Address: Institute Cellular Medicine, Level 4 Leech Building; Newcastle University, Framlington Place, Newcastle Upon Tyne, UK. [email protected] Email addresses: [email protected] (A. Leitch), [email protected] (A. Lakey), [email protected] (W. Hotham), [email protected] (L Aguis), , [email protected] (G Kass), [email protected] (P. Blain) [email protected] (M. Wright). Abbreviations AhR, aryl hydrocarbon receptor; ICI182780, also known as fulvestrant; E2, 17β estradiol; EE, ethinylestradiol; ERα, estrogen receptor alpha, also known as NR3A1; ERβ, estrogen receptor beta, also known as ER3A2; M8OI, 1-octyl-3-methylimidazolium chloride, also known as C8min; PBC, primary biliary cholangitis; PPARα, peroxisome proliferator activated receptor alpha; TFF1, trefoil factor 1. 2 ABSTRACT Recent environmental sampling around a landfill site in the UK demonstrated that unidentified xenoestrogens were present at higher levels than control sites; that these xenoestrogens were capable of super-activating (resisting ligand-dependent antagonism) the murine variant 2 ERβ and that the ionic liquid 1-octyl-3-methylimidazolium chloride (M8OI) was present in some samples.
    [Show full text]
  • Memorandum Date: June 6, 2014
    DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration Memorandum Date: June 6, 2014 From: Bisphenol A (BPA) Joint Emerging Science Working Group Smita Baid Abraham, M.D. ∂, M. M. Cecilia Aguila, D.V.M. ⌂, Steven Anderson, Ph.D., M.P.P.€* , Jason Aungst, Ph.D.£*, John Bowyer, Ph.D. ∞, Ronald P Brown, M.S., D.A.B.T.¥, Karim A. Calis, Pharm.D., M.P.H. ∂, Luísa Camacho, Ph.D. ∞, Jamie Carpenter, Ph.D.¥, William H. Chong, M.D. ∂, Chrissy J Cochran, Ph.D.¥, Barry Delclos, Ph.D.∞, Daniel Doerge, Ph.D.∞, Dongyi (Tony) Du, M.D., Ph.D. ¥, Sherry Ferguson, Ph.D.∞, Jeffrey Fisher, Ph.D.∞, Suzanne Fitzpatrick, Ph.D. D.A.B.T. £, Qian Graves, Ph.D.£, Yan Gu, Ph.D.£, Ji Guo, Ph.D.¥, Deborah Hansen, Ph.D. ∞, Laura Hungerford, D.V.M., Ph.D.⌂, Nathan S Ivey, Ph.D. ¥, Abigail C Jacobs, Ph.D.∂, Elizabeth Katz, Ph.D. ¥, Hyon Kwon, Pharm.D. ∂, Ifthekar Mahmood, Ph.D. ∂, Leslie McKinney, Ph.D.∂, Robert Mitkus, Ph.D., D.A.B.T.€, Gregory Noonan, Ph.D. £, Allison O’Neill, M.A. ¥, Penelope Rice, Ph.D., D.A.B.T. £, Mary Shackelford, Ph.D. £, Evi Struble, Ph.D.€, Yelizaveta Torosyan, Ph.D. ¥, Beverly Wolpert, Ph.D.£, Hong Yang, Ph.D.€, Lisa B Yanoff, M.D.∂ *Co-Chair, € Center for Biologics Evaluation & Research, £ Center for Food Safety and Applied Nutrition, ∂ Center for Drug Evaluation and Research, ¥ Center for Devices and Radiological Health, ∞ National Center for Toxicological Research, ⌂ Center for Veterinary Medicine Subject: 2014 Updated Review of Literature and Data on Bisphenol A (CAS RN 80-05-7) To: FDA Chemical and Environmental Science Council (CESC) Office of the Commissioner Attn: Stephen M.
    [Show full text]
  • Adverse Effects of Digoxin, As Xenoestrogen, on Some Hormonal and Biochemical Patterns of Male Albino Rats Eman G.E.Helal *, Mohamed M.M
    The Egyptian Journal of Hospital Medicine (October 2013) Vol. 53, Page 837– 845 Adverse Effects of Digoxin, as Xenoestrogen, on Some Hormonal and Biochemical Patterns of Male Albino Rats Eman G.E.Helal *, Mohamed M.M. Badawi **,Maha G. Soliman*, Hany Nady Yousef *** , Nadia A. Abdel-Kawi*, Nashwa M. G. Abozaid** Department of Zoology, Faculty of Science, Al-Azhar University (Girls)*, Department of Biochemistry, National organization for Drug Control and Research** Department of Biological and Geological Sciences, Faculty of Education, Ain Shams University*** Abstract Background: Xenoestrogens are widely used environmental chemicals that have recently been under scrutiny because of their possible role as endocrine disrupters. Among them is digoxin that is commonly used in the treatment of heart failure and atrial dysrhythmias. Digoxin is a cardiac glycoside derived from the foxglove plant, Digitalis lanata and suspected to act as estrogen in living organisms. Aim of the work: The purpose of the current study was to elucidate the sexual hormonal and biochemical patterns of male albino rats under the effect of digoxin treatment. Material and Methods: Forty six male albino rats (100-120g) were divided into three groups (16 rats for each). Half of the groups were treated daily for 15 days and the other half for 30 days. Control group: Animals without any treatment. Digoxin L group: orally received digoxin at low dose equivalent of 0.0045mg/200g.b.wt. Digoxin H group: administered digoxin orally at high dose equivalent of 0.0135mg/200g.b.wt. At the end of the experimental periods, blood was collected and serum was separated for estimation the levels of prolactin (PRL), FSH, LH, total testosterone (total T), aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), urea, creatinine, total proteins, albumin, total lipids, total cholesterol (total-chol), Triglycerides (TG), low density lipoprotein cholesterol (LDL-chol) and high density lipoprotein cholesterol (HDL-chol).
    [Show full text]
  • Estrogen Receptors in Polycystic Ovary Syndrome
    cells Review Estrogen Receptors in Polycystic Ovary Syndrome Xue-Ling Xu 1,†, Shou-Long Deng 2,3,†, Zheng-Xing Lian 1,* and Kun Yu 1,* 1 College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; [email protected] 2 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Ministry of Health, Beijing 100021, China; [email protected] 3 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China * Correspondence: [email protected] (Z.-X.L.); [email protected] (K.Y.) † These authors contributed equally to this work. Abstract: Female infertility is mainly caused by ovulation disorders, which affect female reproduction and pregnancy worldwide, with polycystic ovary syndrome (PCOS) being the most prevalent of these. PCOS is a frequent endocrine disease that is associated with abnormal function of the female sex hormone estrogen and estrogen receptors (ERs). Estrogens mediate genomic effects through ERα and ERβ in target tissues. The G-protein-coupled estrogen receptor (GPER) has recently been described as mediating the non-genomic signaling of estrogen. Changes in estrogen receptor signaling pathways affect cellular activities, such as ovulation; cell cycle phase; and cell proliferation, migration, and invasion. Over the years, some selective estrogen receptor modulators (SERMs) have made substantial strides in clinical applications for subfertility with PCOS, such as tamoxifen and clomiphene, however the role of ER in PCOS still needs to be understood. This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus, and the clinical application of related targeted small-molecule drugs.
    [Show full text]
  • Structural and Mechanistic Insights Into Bisphenols Action Provide Guidelines for Risk Assessment and Discovery of Bisphenol a Substitutes
    Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes Vanessa Delfossea, Marina Grimaldib, Jean-Luc Ponsa, Abdelhay Boulahtoufb, Albane le Mairea, Vincent Cavaillesb, Gilles Labessea, William Bourgueta,1,2, and Patrick Balaguerb,1,2 aCentre de Biochimie Structurale, Institut National de la Santé et de la Recherche Médicale U1054, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5048, Universités Montpellier 1 and 2, 34090 Montpellier, France; and bInstitut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale U896, Centre Régional de Lutte contre le Cancer Val d’Aurelle Paul Lamarque, Université Montpellier 1, 34298 Montpellier, France Edited* by Jan-Åke Gustafsson, Karolinska Institutet, Huddinge, Sweden, and approved August 2, 2012 (received for review March 1, 2012) Bisphenol A (BPA) is an industrial compound and a well known onset of obesity and other metabolic syndromes (9). In this regard, endocrine-disrupting chemical with estrogenic activity. The wide- a large body of data about endocrine-disrupting chemicals (EDCs) spread exposure of individuals to BPA is suspected to affect a variety underlines the importance of exposure during early stages of de- of physiological functions, including reproduction, development, and velopment, which could result in numerous biological defects in metabolism. Here we report that the mechanisms by which BPA and adult life (10). two congeners, bisphenol AF and bisphenol C (BPC), bind to and The molecular basis behind the deleterious effects of BPA is poorly understood, and a large controversy has been created activate estrogen receptors (ER) α and β differ from that used by 17β- within the field of endocrine disruption about low doses’ effects estradiol.
    [Show full text]
  • Expressomal Approach for Comprehensive Analysis and Visualization of Ligand Sensitivities of Xenoestrogen Responsive Genes
    Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes Toshi Shiodaa,b,1, Noël F. Rosenthala, Kathryn R. Cosera, Mizuki Sutoa, Mukta Phatakc, Mario Medvedovicc, Vincent J. Careyb,d, and Kurt J. Isselbachera,b,1 aMolecular Profiling Laboratory, Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129; bDepartment of Medicine, Harvard Medical School, Boston, MA 02115; cLaboratory for Statistical Genomics and Systems Biology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and dChanning Laboratory, Brigham and Women’s Hospital, Boston, MA 02115 Contributed by Kurt J. Isselbacher, August 26, 2013 (sent for review June 17, 2013) Although biological effects of endocrine disrupting chemicals Evidence is accumulating that the EDCs may cause significant (EDCs) are often observed at unexpectedly low doses with occa- biological effects in humans or animals at doses far lower than sional nonmonotonic dose–response characteristics, transcriptome- the exposure limits set by regulatory agencies (8, 9). In addition wide profiles of sensitivities or dose-dependent behaviors of the to such low-dose effects, an increasing number of studies also EDC responsive genes have remained unexplored. Here, we describe support the concept of the nonmonotonic EDC effects, whose dose–response curves show U shapes or inverted-U shapes (8- expressome analysis for the comprehensive examination of dose- – dependent gene responses
    [Show full text]
  • Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens
    International Journal of Molecular Sciences Review Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens Anna Helena Mazurek 1 , Łukasz Szeleszczuk 1,* , Thomas Simonson 2 and Dariusz Maciej Pisklak 1 1 Chair and Department of Physical Pharmacy and Bioanalysis, Department of Physical Chemistry, Medical Faculty of Pharmacy, University of Warsaw, Banacha 1 str., 02-093 Warsaw Poland; [email protected] (A.H.M.); [email protected] (D.M.P.) 2 Laboratoire de Biochimie (CNRS UMR7654), Ecole Polytechnique, 91-120 Palaiseau, France; [email protected] * Correspondence: [email protected]; Tel.: +48-501-255-121 Received: 21 July 2020; Accepted: 1 September 2020; Published: 3 September 2020 Abstract: In this review, applications of various molecular modelling methods in the study of estrogens and xenoestrogens are summarized. Selected biomolecules that are the most commonly chosen as molecular modelling objects in this field are presented. In most of the reviewed works, ligand docking using solely force field methods was performed, employing various molecular targets involved in metabolism and action of estrogens. Other molecular modelling methods such as molecular dynamics and combined quantum mechanics with molecular mechanics have also been successfully used to predict the properties of estrogens and xenoestrogens. Among published works, a great number also focused on the application of different types of quantitative structure–activity relationship (QSAR) analyses to examine estrogen’s structures and activities. Although the interactions between estrogens and xenoestrogens with various proteins are the most commonly studied, other aspects such as penetration of estrogens through lipid bilayers or their ability to adsorb on different materials are also explored using theoretical calculations.
    [Show full text]
  • Colosorm2003-Endosulfan.Pdf
    Endosulfan: a hidden menace. Item Type Journal Contribution Authors Coloso, Relicardo M. Download date 02/10/2021 12:15:35 Link to Item http://hdl.handle.net/1834/8913 AsianSEAFDEC Aquaculture Volume XXV Number 2 April - June 2003 ISSN 0115-4974 ASEAN-SEAFDEC 5-YEAR PROGRAM Integrated Regional Aquaculture Project Endosulfan: a hidden menace Relicardo M. Coloso, Ph.D. Scientist II, SEAFDEC/AQD rmcoloso@ aqd.seafdec.org.ph The use of pesticides in agriculture and human health has been successful in controlling pests and diseases. The application of the organochlorine pesticides such as DDT [ 1, 1, 1-trichloro-2-2-bis(parachlorophenyl)ethane] against the malaria mosquito and many other insect pests provided a cheap and effective control for most insect problems. The new pesticide technology also brought in other effective agents such as herbicides (for weeds), avicides (for birds), piscicides (for fish), and molluscicides (for snails) that contributed to the success of farming systems worldwide. But pesticide application has many problems such as the emergence of new pests, persistence in the environment, environmental contamination, and subsequent effect on non-target organismsIRAP activity launched including humans. b y W G Yapa n dV T Sulit The chemical structure of endosulfan. After some delay due to various reasons the Endosulfan is highly toxic; it is either latest of which was the SARS outbreak, the restricted, not allowed in ricefields, Integrated Regional Aquaculture Project or banned in Southeast Asian (IRAP) under the ASEAN-SEAFDEC Special countries. Illegal trade and incorrect use 5-year Program had a soft launching with the (eg. to control golden apple snail in rice first phase of the site visitation and survey con­ paddies) always pose added danger ducted from 12 to 23 May 2003.
    [Show full text]
  • Downloaded from Bioscientifica.Com at 09/25/2021 07:25:42PM Via Free Access 244 H WATANABE and Others · Genomic Effects of Nonylphenol
    243 Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol H Watanabe, A Suzuki, M Goto, D B Lubahn1, H Handa2 and T Iguchi Center for Integrative Bioscience, Okazaki National Research Institutes, 5-1 Higashiyama, Myodaiji, Okazaki 444-8585, Japan and Core Research for Evolution Science and Technology (CREST), Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan 1Department of Molecular Biology, University of Missouri, Columbia, Missouri 65211, USA 2Frontier Collaborative Research Center, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Yokohama, Kanagawa 226-8503, Japan (Requests for offprints should be addressed to T Iguchi; Email: [email protected]) Abstract Alkylphenols perturb the endocrine system and are considered to have weak estrogenic activities. Although it is known that nonylphenol can bind weakly to the estrogen receptor, it is unclear whether all reported effects of nonylphenol are attributable to its estrogen receptor-binding activity. In order to examine whether alkylphenols have similar effects to the natural hormone, estradiol, we used a mouse model to examine the effects of nonylphenol on gene expression and compared it with estradiol. DNA microarray analysis revealed that, in the uterus, most of the genes activated by this alkylphenol at a high dose (50 mg/kg) were also activated by estradiol. At lower doses, nonylphenol (0·5 mg/kg and 5 mg/kg) had little effect on the genes that were activated by estradiol. Thus, we concluded that the effects of nonylphenol at a high dose (50 mg/kg) were very similar to estradiol in uterine tissue. Moreover, since evaluation of estrogenic activity by gene expression levels was comparable with the uterotrophic assay, it indicated that analysis of gene expression profiles can predict the estrogenic activities of chemicals.
    [Show full text]
  • NF-B—An Important Player in Xenoestrogen Signaling in Immune
    cells Review NF-κB—An Important Player in Xenoestrogen Signaling in Immune Cells Karolina Nowak * , Ewa Jabło ´nskaand Wioletta Ratajczak-Wrona Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland; [email protected] (E.J.); [email protected] (W.R.-W.) * Correspondence: [email protected] Abstract: The proper functioning of the immune system is critical for an effective defense against pathogenic factors such as bacteria and viruses. All the cellular processes taking place in an organism are strictly regulated by an intracellular network of signaling pathways. In the case of immune cells, the NF-κB pathway is considered the key signaling pathway as it regulates the expression of more than 200 genes. The transcription factor NF-κB is sensitive to exogenous factors, such as xenoestrogens (XEs), which are compounds mimicking the action of endogenous estrogens and are widely distributed in the environment. Moreover, XE-induced modulation of signaling pathways may be crucial for the proper development of the immune system. In this review, we summarize the effects of XEs on the NF-κB signaling pathway. Based on our analysis, we constructed a model of XE-induced signaling in immune cells and found that in most cases XEs activate NF-κB. Our analysis indicated that the indirect impact of XEs on NF-κB in immune cells is related to the modulation of estrogen signaling and other pathways such as MAPK and JAK/STAT. We also summarize the role of these aspects of signaling in the development and further functioning of the immune system in this paper.
    [Show full text]
  • Genistein, a Soy Phytoestrogen, Prevents the Growth of BG-1 Ovarian Cancer Cells Induced by 17Β-Estradiol Or Bisphenol a Via the Inhibition of Cell Cycle Progression
    INTERNATIONAL JOURNAL OF ONCOLOGY 42: 733-740, 2013 Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17β-estradiol or bisphenol A via the inhibition of cell cycle progression KYUNG-A HWANG, NAM-HEE KANG, BO-RIM YI, HYE-RIM LEE, MIN-AH PARK and KYUNG-CHUL CHOI Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea Received September 19, 2012; Accepted November 2, 2012 DOI: 10.3892/ijo.2012.1719 Abstract. An endocrine disrupting chemical (EDC) is a global E3 is the most plentiful among these three factors, E2, also health concern. In this study, we examined the effects of genis- known as 17β-estradiol, exerts the strongest estrogenic effect. tein (GEN) on bisphenol A (BPA) or 17β-estradiol (E2)-induced Estrogens are produced in ovaries, adrenal glands, and fat cell growth and gene alterations of BG-1 ovarian cancer cells tissues, and function as the primary female sex hormones that expressing estrogen receptors (ERs). In an in vitro cell viability promote the development of secondary sexual characteristics assay, E2 or BPA significantly increased the growth of BG-1 and regulate certain functions of the reproductive system. cells. This increased proliferative activity was reversed by treat- In addition, these compounds control various metabolic ment with ICI 182,780, a well-known ER antagonist, while cell processes including bone growth, protein synthesis, and fat proliferation was further promoted in the presence of propyl deposition. Estrogens have also been reported to be linked to pyrazole triol (PPT), an ERα agonist.
    [Show full text]
  • Endosulfan Final Review Report and Regulatory Decision
    ENDOSULFAN FINAL REVIEW REPORT AND REGULATORY DECISION JUNE 2005 Volume II. Occupational Health & Safety technical report Endocrine Disruption technical report TABLE OF CONTENTS 9. OH&S ASSESSMENT TECHNICAL REPORT.......................................................................... 108 9.1 BACKGROUND........................................................................................................................ 108 9.2 DERMAL ABSORPTION........................................................................................................... 108 9.2.1 In vivo studies..................................................................................................................................108 9.2.2 In vitro studies .................................................................................................................................109 9.2.3 Dermal absorption factor for exposure to concentrates and spray mixtures....................................110 9.2.4 Dermal absorption factor for re-entry exposure ..............................................................................110 9.3 OCCUPATIONAL EXPOSURE STUDIES.................................................................................... 111 9.3.1 Parameters used in exposure studies................................................................................................112 9.4 OCCUPATIONAL RISK ASSESSMENT ..................................................................................... 134 9.4.1 Margin of Exposure .........................................................................................................................134
    [Show full text]