Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay
01 Aug 2000-Journal of Health Science (The Pharmaceutical Society of Japan)-Vol. 46, Iss: 4, pp 282-298
TL;DR: A simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators to test the estrogenic activity of chemicals.
Abstract: One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.
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TL;DR: This study demonstrated that through in vitro metabolism assessment, the estrogenic activity of chemical substances could be directly detected in terms of VTG secretion in primary-cultured Xenopus hepatocyte assay using adult male Xenopus laevis.
Abstract: Estrogenic activity of phthalate esters in dental soft resins was evaluated with an amphibian system consisting of a vitellogenin (VTG)-detecting Enzyme-Linked Immunosorbent Assay and a primary-cultured hepatocyte assay using adult male Xenopus laevis. In particular, phthalate esters--Di-n-butyl phthalate (DBP), Butyl phthalyl butyl glycolate (BPBG), Benzyl butyl phthalate (BBP), and Benzyl benzoate (BB)--were investigated. Bisphenol A (BPA) was prepared for comparison with these chemicals, and 17beta-estradiol (E2) was used as a positive control. The chemicals were diluted in dimethyl sulfoxide (DMSO) to obtain final concentrations ranging from 10(-11) to 10(-4) mol/l. BPA induced estrogenic activity at a concentration of 1.1x10(-6) mol/l, while E2 showed at 4.1x10(-11) mol/l. DBP, BBP, BB, and BPBG showed no estrogenic activity at concentrations between 4x10(-7) mol/l and 1x10(-4) mol/l. The latter result indicated that these phthalate esters might be metabolically transformed into non-estrogenic substances in Xenopus hepatocytes. Furthermore, this study demonstrated that through in vitro metabolism assessment, the estrogenic activity of chemical substances could be directly detected in terms of VTG secretion in primary-cultured Xenopus hepatocytes.
18 citations
TL;DR: The present study describes both the final MEOGRT protocol that has been published by the USEPA and the OECD, and the iterations that provided valuable insights into nuances of the protocol.
Abstract: In response to various legislative mandates, the US Environmental Protection Agency (USEPA) formed its Endocrine Disruptor Screening Program (EDSP), which in turn, formed the basis of a tiered testing strategy to determine the potential of pesticides, commercial chemicals, and environmental contaminants to disrupt the endocrine system. The first tier of tests is intended to detect the potential for endocrine disruption mediated through estrogen, androgen, or thyroid pathways, whereas the second tier is intended to further characterize the effects on these pathways and to establish a dose-response relationship for adverse effects. One of these tier 2 tests, the Medaka Extended One Generation Reproduction Test (MEOGRT), was developed by the USEPA for the EDSP and, in collaboration with the Japanese Ministry of the Environment, for the Guidelines for the Testing of Chemicals of the Organisation for Economic Co-operation and Development (OECD). The MEOGRT protocol was iteratively modified based on knowledge gained after the successful completion of 9 tests with variations in test protocols. The present study describes both the final MEOGRT protocol that has been published by the USEPA and the OECD, and the iterations that provided valuable insights into nuances of the protocol. The various tests include exposure to 17β-estradiol, 4-t-octylphenol, o,p'- dichlorodiphenyltrichloroethane, 4-chloro-3-methylphenol, tamoxifen, 17β-trenbolone, vinclozolin, and prochloraz. Environ Toxicol Chem 2017;36:3387-3403. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
18 citations
Cites background from "Estrogenic Activities of 517 Chemic..."
...It has also been shown to bind to the ER in a yeast 2-hybrid assay [50]....
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TL;DR: The results of this study indicate that endocrine disruption exists in tilapias from Rio and Limon lakes, and that exposure to HCB and BaP could be causing these alterations.
Abstract: Vitellogenin (Vtg), 17β-estradiol (E2) and testosterone (T) were used as biomarkers of endocrine disruption in mature male nile tilapia (Oreochromis niloticus) from three lakes (Rio, Enmedio and Limon) in Chiapas, Mexico. Vitellogenesis induction was found in tilapias from Rio and Limon, moderately high E2 levels in Rio and Limon tilapias, compared with controls (cultured tilapias). Significant correlations between benzo(a)pyrene (BaP) metabolites and hexachlorobenzene (HCB) with Vtg and E2 were found. The results of this study indicate that endocrine disruption exists in tilapias from Rio and Limon lakes, and that exposure to HCB and BaP could be causing these alterations.
17 citations
TL;DR: In this paper, the presence of endocrine disruptors such as alkylphenols, phthalates and styrene oligomers in diesel and gasoline exhaust particulate matter were determined simultaneously by gas chromatography/mass spectrometry (GC/MS).
Abstract: Thirty-one endocrine disruptors, including alkylphenols, phthalates and styrene oligomers, in diesel and gasoline exhaust particulate matter were determined simultaneously by gas chromatography/mass spectrometry (GC/MS). When particulate matter was subjected to Soxhlet extraction and Kuderna-Danish concentration, four phthalates, an adipate and five styrene trimers were found to exist as contaminants from the ambient air. Regarding the other 21 compounds, only benzo[a]pyrene and n-pentylphenol were detected in the range of 0.5-11 and 0.1-1.1 μg/km driving distance, respectively, from both diesel and gasoline exhaust particulate matter. When particulate matter was subjected to only ultrasonic extraction, the above phthalates, adipate and styrene trimers were not detected as contaminants from the ambient air. Using this treatment method, the above phthalates, adipate and styrene trimers were not detected in either of the two types of exhaust particulate matter. The above results revealed that the presence of such endocrine disruptors as benzo[a]pyrene and n-pentylphenol in diesel and gasoline exhaust particulate matter must be investigated in greater detail. Furthermore, it becomes clear that prevention of contamination during sample pretreatment is necessary.
17 citations
TL;DR: It is indicated that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning andMemory in female rats only.
Abstract: Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.
17 citations
References
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Book•
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01 Jan 1996
TL;DR: The cause of disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure, is traced to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system.
Abstract: For years, scientists have noticed disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure. Humans are not immune either, with sperm counts dropping by as much as 50% in recent decades and with women seeing a rise in hormone-related cancers, endometriosis and other disorders. This book traces the cause of these aberrations and diseases to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system. The conclusions are as obvious as they are inescapable - unless we make vital changes in the way we manufacture and employ the artefacts of our "good life", there will be no life at all.
917 citations