Use of fluorine-18-BPA PET images and image registration to enhance radiation treatment planning for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Khan, Mohammad Khurram

The Monte-Carlo based simulation environment for radiation therapy (SERA) software is used to simulate the dose administered to a patient undergoing boron neutron capture therapy (BNCT). Point sampling of tumor tissue results in an estimate of a uniform boron concentration scaling factor of 3.5. Under conventional treatment protocols, this factor is used to scale the boron component of the dose linearly and homogenously within the tumor and target volumes. The average dose to the tumor cells by such a method could be improved by better methods of quantifying the in-vivo 10B biodistribution. A better method includes radiolabeling para-Boronophenylalanine (p-BPA) with 18F and imaging the pharmaceutical using positron emission tomography (PET). This biodistribution of 18F-BPA can then be used to better predict the average dose delivered to the tumor regions. This work uses registered 18F-BPA PET images to incorporate the in-vivo boron biodistribution within current treatment planning. The registered 18F-BPA PET images are then coupled in a new computer software, PET2MRI.m, to linearly scale the boron component of the dose. A qualititative and quantitative assessment of the dose contours is presented using the two approaches. Tumor volume, tumor axial extent, and target locations are compared between using MRI or PET images to define the tumor volume. In addition, peak-to-normal brain value at tumor axial center is determined for pre and post surgery patients using 18F-BPA PET images. The differences noted between the registered GBM tumor volumes (range: 34.04--136.36%), tumor axial extent (range: 20--150%), and the beam target location (1.27--4.29 cm) are significantly different. The peak-to-normal brain values are also determined at the tumor axial center using the 18F-BPA PET images. The peak-to-normal brain values using the last frame of the pre-surgery study for the GBM patients ranged from 2.05--3.4. For post surgery time weighted PET data, the peak

BPA Facts

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

The Bonneville Power Administration is a federal nonprofit power marketing administration based in the Pacific Northwest . Although BPA is part of the U .S . Department of Energy, it is self-funding and covers its costs by selling its products and services . BPA markets wholesale electrical power from 31 federal hydro projects in the Columbia River Basin, one nonfederal nuclear plant and several small nonfederal power plants . The dams are operated by the U .S . Army Corps of Engineers and the Bureau of Reclamation . About 30 percent of the electric power used in the Northwest comesmore » from BPA . BPA’s resources — primarily hydroelectric — make its power nearly carbon free . BPA also operates and maintains about three- fourths of the high-voltage transmission in its service territory . BPA’s service territory includes Idaho, Oregon, Washington, western Montana and small parts of eastern Montana, California, Nevada, Utah and Wyoming . BPA promotes energy efficiency, renewable resources and new technologies that improve its ability to deliver on its mission . BPA also funds regional efforts to protect and enhance fish and wildlife populations affected by hydropower development in the Columbia River Basin . BPA is committed to public service and seeks to make its decisions in a manner that provides opportunities for input from stakeholders . In its vision statement, BPA dedicates itself to providing high system reliability, low rates consistent with sound business principles, environmental stewardship and accountability« less

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

PubMed

Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

2016-11-08

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [ 18 F]-L-FBPA, an 18 F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [ 18 F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [ 19 F]-L-FBPA as alternatives to [ 18 F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [ 19 F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [ 19 F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [ 19 F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [ 19 F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to

Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight.

PubMed

Rehan, Mohd; Ahmad, Ejaz; Sheikh, Ishfaq A; Abuzenadah, Adel M; Damanhouri, Ghazi A; Bajouh, Osama S; AlBasri, Samera F; Assiri, Mansour M; Beg, Mohd A

2015-01-01

Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR

Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene—A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight

PubMed Central

Rehan, Mohd; Ahmad, Ejaz; Sheikh, Ishfaq A.; Abuzenadah, Adel M.; Damanhouri, Ghazi A.; Bajouh, Osama S.; AlBasri, Samera F.; Assiri, Mansour M.; Beg, Mohd A.

2015-01-01

Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR

Cytotoxicity measurement of Bisphenol A (BPA) and its substitutes using human keratinocytes.

PubMed

Son, Seogho; Nam, KeeSoo; Kim, Hyungjoo; Gye, Myung Chan; Shin, Incheol

2018-07-01

Bisphenol-A (BPA) was first synthesized in the 1890s and has been used in many plastic products. However, BPA is known to act as an endocrine disruptor and has been found to be toxic to human health. Many alternative substances have been developed to replace BPA, but it is still widely used worldwide. In this study, we identified the potential cytotoxicity of BPA by evaluating toxicity using human keratinocytes. Also, we evaluated cytotoxicity of BPA substitutes to determine their suitability as an alternative to BPA. The proliferation assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and western blot analysis showed that BPA significantly affect cell viability, induction of apoptotic fraction and increased activation of DNA-damage marker protein. In addition, through the same experiments, the substitutes of BPA were shown to be significantly less toxic than BPA, and the least toxicity was observed with 1,4-cyclohexanedimethanol (CHDM) and terephthalic acid (TPA). In conclusion, this study suggests that cytotoxicity of BPA induces apoptosis of human keratinocytes, and that CHDM and TPA are the most suitable substitutes for BPA. Copyright © 2018 Elsevier Inc. All rights reserved.

Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium.

PubMed

Morris, G M; Coderre, J A; Hopewell, J W; Micca, P L; Rezvani, M

1994-08-01

The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal skin of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma spectrometry, revealed comparable levels of boron-10 (10B) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The 10B content of blood (12.0 +/- 0.5 micrograms/g) was slightly higher than that of skin (10.0 +/- 0.5 micrograms/g) after oral dosing with BPA. Biphasic skin reactions were observed after irradiation with the thermal neutron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was approximately 2 weeks. The time at which the second-wave skin reaction, dermal necrosis, became evident was dose-related and occurred after a latent interval of > or = 24 weeks, well after the acute epithelial reaction had healed. The incidence of both phases of skin damage was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED50 values) were calculated from dose-effect curves and these values were used to determine relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for both moist desquamation and dermal necrosis. It was concluded on the basis of these calculations that the microdistribution of the two neutron capture agents had a critical bearing on the overall biological effect after thermal neutron activation. BSH, which was possibly excluded from the cytoplasm of epidermal cells, had a low CBE factor value (0.56 +/- 0.06) while BPA, which may be selectively accumulated in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For the dermal reaction, where vascular endothelial cells represent the likely target cell population, the CBE factor values were comparable, at 0.73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

PubMed

Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

2017-01-23

Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma. We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED. In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant. Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.

Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for boron neutron capture therapy: safety dose evaluation by a battery of cytotoxicity tests.

PubMed

De Simone, U; Manzo, L; Ferrari, C; Bakeine, J; Locatelli, C; Coccini, T

2013-03-01

Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0-100μgBeq/ml) after short- and long-term exposure (4-48h and 7-10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15-40% at doses ranging 20-100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential BPA levels in sewage wastewater effluents from metro Detroit communities.

PubMed

Santos, Julia M; Putt, David A; Jurban, Michael; Joiakim, Aby; Friedrich, Klaus; Kim, Hyesook

2016-10-01

The endocrine disruptor Bisphenol A (BPA) is ubiquitous in both aquatic and surface sediment environments because it is continuously released into sewage wastewater effluent. The measurement of BPA at wastewater treatment plants is rarely performed even though the United States Environmental Protection Agency (EPA) states that current levels of environmental BPA could be a threat to aquatic organisms. Therefore, the aims of this study were to measure BPA levels in sewage wastewater at different collection points over a 1-year period and to compare the levels of BPA to 8-isoprostane, a human derived fatty acid, found in sewage wastewater. We analyzed pre-treated sewage samples collected from three source points located in different communities in the metropolitan Detroit area provided by the Detroit Water and Sewerage Department. Human urine samples were also used in the study. BPA and 8-isoprostane were measured using ELISA kits from Detroit R&D, Inc. BPA levels from the same collection point oscillated more than 10-fold over 1 year. Also, BPA levels fluctuated differentially at each collection point. Highly fluctuating BPA values were confirmed by LC/MS/MS. The concentration of BPA in sewage wastewater was ~100-fold higher than the concentration of 8-isoprostane, while urinary concentration was ~20-fold higher. Thus, BPA levels discharged into the sewage network vary among communities, and differences are also observed within communities over time. The difference in BPA and 8-isoprostane levels suggest that most of the BPA discharged to sewage wastewater might be derived from industries rather than from human urine. Therefore, the continuous monitoring of BPA could account for a better regulation of BPA release into a sewage network.

BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

PubMed

Klenke, Ulrike; Constantin, Stephanie; Wray, Susan

2016-05-01

Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50μM BPA significantly decreased GnRH calcium activity. Blockage of γ-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-β, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-γ, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-γ, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons.

BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway

PubMed Central

Klenke, Ulrike; Constantin, Stephanie

2016-01-01

Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50μM BPA significantly decreased GnRH calcium activity. Blockage of γ-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-β, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-γ, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-γ, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons. PMID:26934298

H₃PW₁₂O₄₀/TiO₂ catalyst-induced photodegradation of bisphenol A (BPA): kinetics, toxicity and degradation pathways.

PubMed

Lu, Nan; Lu, Ying; Liu, Fangyuan; Zhao, Kun; Yuan, Xing; Zhao, Yahui; Li, Yuan; Qin, Hongwei; Zhu, Jia

2013-05-01

A series of experiments were conducted to investigate the kinetics of bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) degradation using H₃PW₁₂O₄₀/TiO₂ (PW₁₂/TiO₂) composite catalyst, toxicity of BPA intermediate products and degradation pathways. The results showed that the BPA photodegradation using PW₁₂/TiO₂ catalyst followed the first-order kinetics, and under the optimal experimental conditions at H₃PW₁₂O₄₀ loading amount of 6.3%, BPA initial concentration of 5 mg L(-1), and the solution pH of 8.2, the kinetic constant was 3.7-fold larger than that of pristine TiO₂. The hydroxyl radicals derived from the electroreduction of dissolved oxygen with electrons via chain reactions was the main reactive oxygen species. According to the identified intermediates, 4-isopropanolphenol, hydroquinone, 4-hydroxybenzoic acid, and phenol, the possible BPA photodegradation pathways were proposed. Upon 12h irradiation, 77% BPA (20 mg L(-1)) was mineralized and the toxicity to Daphnia magna (D. magna) was almost disappeared, implying the strong oxidation ability of PW₁₂/TiO₂ catalyst. The studies provide important information about the BPA degradation and promote the technical development for BPA removal. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity

PubMed Central

2014-01-01

Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA's impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. PMID:24804084

Effects of bisphenol A (BPA) on placentation and survival of the neonates in mice.

PubMed

Tachibana, Toru; Wakimoto, Yuki; Nakamuta, Nobuaki; Phichitraslip, Thanmaporn; Wakitani, Shoichi; Kusakabe, Ken; Hondo, Eiichi; Kiso, Yasuo

2007-06-01

The effects of bisphenol A (BPA) on placentation have not been fully determined. The aim of this study was to clarify the structural changes of the placenta, abortion rate, and survival of neonates after BPA administration in mice. BPA (10 mg/kg/day) was administered to pregnant mice (BPA mice) subcutaneously from the first day of pregnancy (Day 0) to Day 7 (8 days total). The number of embryos and weights of whole uteri were measured on Days 10 and 12. Morphological changes in the placentae were examined by light microscopy on the corresponding days of pregnancy. The number of neonates was also counted. Survival rates were periodically calculated for neonates from the first day after parturition (P-Day 0) to P-Day 56. The number of embryos and weight of the uterus on Days 10 and 12 were significantly decreased by BPA injection. No notable differences were recognized between the left and right uteri. The proportion of the labyrinthine zone per whole placenta in the BPA mice became lower than that in the controls, and that of the metrial gland was higher in the BPA mice. The intervillous spaces of the placenta were narrower in the BPA mice. Degenerative changes were found in the trophoblastic giant cells and spongiotrophoblast layers of the BPA mice. The number of BPA mouse neonates was drastically decreased within 3 days after birth, and no mice survived after P-Day 56. The results suggest that BPA not only disrupts placental functions and leads to abortion through chronic stimulation of gene expression by binding to DNA but that it also affects the mortality of neonates through indirect exposure of embryos.

Bisphenol A (BPA) in the serum of pet dogs following short-term consumption of canned dog food and potential health consequences of exposure to BPA.

PubMed

Koestel, Zoe L; Backus, Robert C; Tsuruta, Kaoru; Spollen, William G; Johnson, Sarah A; Javurek, Angela B; Ellersieck, Mark R; Wiedmeyer, Charles E; Kannan, Kurunthachalam; Xue, Jingchuan; Bivens, Nathan J; Givan, Scott A; Rosenfeld, Cheryl S

2017-02-01

Bisphenol A (BPA) is a widely present endocrine disruptor chemical found in many household items. Moreover, this chemical can bioaccumulate in various terrestrial and aquatic sources; thereby ensuring continual exposure of animals and humans. For most species, including humans, diet is considered the primary route of exposure. However, there has been little investigation whether commercial-brands of dog foods contain BPA and potential health ramifications of BPA-dietary exposure in dogs. We sought to determine BPA content within dog food, whether short-term consumption of these diets increases serum concentrations of BPA, and potential health consequences, as assessed by potential hematological, serum chemistry, cortisol, DNA methylation, and gut microbiome changes, in dogs associated with short-term dietary exposure to BPA. Fourteen healthy privately-owned dogs were used in this study. Blood and fecal samples were collected prior to dogs being placed for two-weeks on one of two diets (with one considered to be BPA-free), and blood and fecal samples were collected again. Serum/plasma samples were analyzed for chemistry and hematology profiles, cortisol concentrations, 5-methylcytosine in lymphocytes, and total BPA concentrations. Fecal samples were used for microbiome assessments. Both diets contained BPA, and after two-weeks of being on either diet, dogs had a significant increase in circulating BPA concentrations (pre-samples=0.7±0.15ng/mL, post-samples=2.2±0.15ng/mL, p<0.0001). Elevated BPA concentrations positively correlated with increased plasma bicarbonate concentrations and associated with fecal microbiome alterations. Short-term feeding of canned dog food increased circulating BPA concentrations in dogs comparable to amounts detected in humans, and greater BPA concentrations were associated with serum chemistry and microbiome changes. Dogs, who share our internal and external environments with us, are likely excellent indicators of potential human health

Molecular Mechanisms of Action of BPA.

PubMed

Acconcia, Filippo; Pallottini, Valentina; Marino, Maria

2015-01-01

Bisphenol A (BPA) exposure has been associated with serious endocrine-disrupting effects in humans and wildlife. Toxicological and epidemiological studies evidenced that BPA increases body mass index and disrupts normal cardiovascular physiology by interfering with endogenous hormones in rodents, nonhuman primates, and cell culture test systems. The BPA concentration derived from these experiments were used by government regulatory agencies to determine the safe exposure levels of BPA in humans. However, accumulating literature in vivo and in vitro indicate that at concentrations lower than that reported in toxicological studies, BPA could elicit a different endocrine-disrupting capacity. To further complicate this picture, BPA effects rely on several and diverse mechanisms that converge upon endocrine and reproductive systems. If all or just few of these mechanisms concur to the endocrine-disrupting potential of low doses of BPA is at present still unclear. Thus, taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of BPA on endocrine system.

Curcumin suppresses JNK pathway to attenuate BPA-induced insulin resistance in LO2 cells.

PubMed

Geng, Shanshan; Wang, Shijia; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Zhu, Jianyun; Jiang, Ye; Yang, Xue; Li, Yuan; Chen, Yue; Wang, Xiaoqian; Meng, Yu; Zhong, Caiyun

2018-01-01

To examine whether curcumin has protective effect on insulin resistance induced by bisphenol A (BPA) in LO2 cells and whether this effect was mediated by inhibiting the inflammatory mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways. LO2 cells were stimulated with BPA in the presence or absence of curcumin for 5 days. Glucose consumption, activation of insulin signaling, MAPKs and NF-κB pathways, levels of inflammatory cytokines and MDA production were analyzed. Curcumin prevented BPA-induced reduction of glucose consumption and suppression of insulin signaling pathway, indicating curcumin alleviated BPA-triggered insulin resistance in LO2 cells. mRNA and proteins levels of TNF-α and IL-6, as well as MDA level in LO2 cells treated with BPA were decreased by curcumin. Furthermore, curcumin downregulated the activation of p38, JNK, and NF-κB pathways upon stimulation with BPA. Inhibition of JNK pathway, but not p38 nor NF-κB pathway, improved glucose consumption and insulin signaling in BPA-treated LO2 cells. Curcumin inhibits BPA-induced insulin resistance by suppressing JNK pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Direct measurement of Bisphenol A (BPA), BPA glucuronide and BPA sulfate in a diverse and low-income population of pregnant women reveals high exposure, with potential implications for previous exposure estimates: a cross-sectional study.

PubMed

Gerona, Roy R; Pan, Janet; Zota, Ami R; Schwartz, Jackie M; Friesen, Matthew; Taylor, Julia A; Hunt, Patricia A; Woodruff, Tracey J

2016-04-12

Bisphenol A (BPA) is a ubiquitous, endocrine-disrupting environmental contaminant that increases risk of some adverse developmental effects. Thus, it is important to characterize BPA levels, metabolic fate and sources of exposure in pregnant women. We used an improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytic method to directly and simultaneously measure unconjugated BPA (uBPA), BPA glucuronide and BPA sulfate in the urine of a population of ethnically and racially diverse, and predominately low-income pregnant women (n = 112) in their second trimester. We also administered a questionnaire on dietary and non-dietary sources of exposure to BPA. We found universal and high exposure to uBPA and its metabolites: median concentrations were 0.25, 4.67, and 0.31 μg/g creatinine for uBPA, BPA glucuronide, and BPA sulfate, respectively. The median Total BPA (uBPA + BPA in glucuronide and sulfate forms) level was more than twice that measured in U.S. pregnant women in NHANES 2005-2006, while 30 % of the women had Total BPA levels above the 95th percentile. On average, Total BPA consisted of 71 % BPA in glucuronide form, 15 % BPA in sulfate form and 14 % uBPA, however the proportion of BPA in sulfate form increased and the proportion of uBPA decreased with Total BPA levels. Occupational and non-occupational contact with paper receipts was positively associated with BPA in conjugated (glucuronidated + sulfated) form after adjustment for demographic characteristics. Recent consumption of foods and beverages likely to be contaminated with BPA was infrequent among participants and we did not observe any positive associations with BPA analyte levels. The high levels of BPA analytes found in our study population may be attributable to the low-income status of the majority of participants and/or our direct analytic method, which yields a more complete evaluation of BPA exposure. We observed near-universal exposure to BPA among pregnant women, as

NIEHS/FDA CLARITY-BPA research program update.

PubMed

Heindel, Jerrold J; Newbold, Retha R; Bucher, John R; Camacho, Luísa; Delclos, K Barry; Lewis, Sherry M; Vanlandingham, Michelle; Churchwell, Mona I; Twaddle, Nathan C; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A; Flaws, Jodi; Howard, Paul C; Walker, Nigel J; Zoeller, R Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T

2015-12-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. Published by Elsevier Inc.

NIEHS/FDA CLARITY-BPA research program update

PubMed Central

Heindel, Jerrold J.; Newbold, Retha R.; Bucher, John R.; Camacho, Luísa; Delclos, K. Barry; Lewis, Sherry M.; Vanlandingham, Michelle; Churchwell, Mona I.; Twaddle, Nathan C.; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A.; Flaws, Jodi; Howard, Paul C.; Walker, Nigel J.; Zoeller, R. Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T.

2016-01-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. PMID:26232693

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

PubMed

Seki, Keiko; Kinashi, Yuko; Takahashi, Sentaro

2015-01-01

The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Higher dermal exposure of cashiers to BPA and its association with DNA oxidative damage.

PubMed

Lv, Yanshan; Lu, Shaoyou; Dai, Yanyan; Rui, Caiyan; Wang, Yongjun; Zhou, Yuanxiu; Li, Yanru; Pang, Qihua; Fan, Ruifang

2017-01-01

Bisphenol A (BPA) is a widely used chemical in the production of many polycarbonate plastics, epoxy resin linings for food and beverage containers and thermal papers. Oral intakes from the contaminated diets were considered as the predominant source of BPA exposure for humans. However, due to the high levels of BPA on thermal receipts and their wide applications in our daily life, the amount of BPA be transferred to the skin after holding thermal paper should not be underestimated, particularly for cashiers. To investigate the contribution of BPA exposure levels via the dermal contact route and the relationship between BPA exposure level and oxidative DNA damage, six male volunteers were recruited and required to simulate the cashiers' work and handle the thermal receipts during the study period. Triclosan (TCS, an antimicrobial compound used widely in personal health and skin care products) was applied as a reference compound. Their urinary BPA, TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were determined by high performance liquid chromatography/ tandem spectrometer (LC/MS/MS). The results showed that after handling the thermal receipts, the urinary BPA concentrations of volunteers increased 3 times of those before the experimental period. But TCS levels in urine kept stable. There existed a correlation between BPA exposure and 8-OHdG (R 2 =0.237, p<0.001), but not between TCS and 8-OHdG concentrations (R 2 =0.026, p<0.777), indicating that more BPA exposure could lead to higher oxidative DNA damage. That the increases in 8-OHdG levels in urine being almost consistent with those of BPA suggested that handling thermal receipts resulted in the increasing BPA intakes and BPA exposure was correlated with DNA oxidative damage. After 48h of the end of handling thermal receipts, the urinary BPA levels did not descend to the levels before experiment, suggesting that the excretion of BPA via dermal contact was over 48h. BPA exposure through dermal contact

An Evaluation of the Relationship among Urine, Air, and Hand Measures of Exposure to Bisphenol A (BPA) in US Manufacturing Workers.

PubMed

Hines, Cynthia J; Christianson, Annette L; Jackson, Matthew V; Ye, Xiaoyun; Pretty, Jack R; Arnold, James E; Calafat, Antonia M

2018-06-13

Exposure to bisphenol A (BPA) can be assessed using external and internal exposure measures. We examined the relationship between two measures of external BPA exposure (air and hand-wipe samples) and one of internal exposure (total BPA in urine) for a group of US manufacturing workers. During 2013-2014, we recruited 78 workers from six US companies that made BPA or made products with BPA. We quantified BPA in seven urine samples, two full-shift air samples and in pre- and end-shift hand-wipe samples collected from workers over 2 consecutive days. We examined correlations between creatinine-corrected urinary concentrations of total BPA (total BPACR) and BPA levels in air and hand wipes using Pearson's correlation coefficient. We also applied mixed-effects regression models to examine the relationship between total BPACR with BPA in air (urine~air model) and with BPA in end-shift hand wipes (urine~hand model), separately and together (urine~air+hand model), after adjusting for covariates. End-shift total BPACR strongly correlated with BPA in air (rp = 0.79, P < 0.0001) and nearly as strongly with BPA in end-shift hand wipes (rp = 0.75, P < 0.0001). In mixed-effect models, BPA air concentration and end-shift hand-wipe BPA level were significantly and positively associated with end-shift total BPACR (P < 0.0001 each). We found a significant effect of the Day 1 BPA air concentration on Day 2 total BPACR (P = 0.0104). When BPA air concentration and end-shift hand-wipe BPA level were in the same model, the air concentration (P < 0.0001) was more significant than the hand-wipe level (P = 0.0106). BPA levels in air and end-shift hand wipes strongly correlated with total BPACR, suggesting that both inhalation and dermal contract were likely exposure routes; however, inhalation, on average, appeared to be a more dominant exposure route than dermal contact for these manufacturing workers.

Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway.

PubMed

Li, Juan; Mao, Rui; Zhou, Qin; Ding, Ling; Tao, Jin; Ran, Mao-Mei; Gao, Er-Sheng; Yuan, Wei; Wang, Jin-Tao; Hou, Li-Fang

2016-01-01

Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 μg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional

High bisphenol A (BPA) concentration in the maternal, but not fetal, compartment increases the risk of spontaneous preterm delivery.

PubMed

Behnia, Faranak; Peltier, Morgan; Getahun, Darios; Watson, Cheryl; Saade, George; Menon, Ramkumar

2016-11-01

The objective of this study is to determine if BPA exposure, as measured by maternal plasma (MP) and amniotic fluid (AF) BPA concentrations is associated with an increased risk of spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM). In this nested case-control study, MP samples from women in term labor (n = 30), preterm labor that ended with preterm delivery (n = 25), or who had pPROM (n = 30) and amniotic fluid samples from term labor (n= 45), preterm labor (n = 60), and pPROM (n = 35) were assayed for BPA by enzyme immunoassay. BPA was detectible in 100% of MP and AF samples. Women with MP BPA concentrations in the fourth quartile were at increased risk of PTB (cOR = 4.12, 95% CI = 1.32-12.87; aOR = 4.78, 95% CI = 1.14-20) but not pPROM. High (fourth quartile) AF BPA values also tended to increase the risk of pPROM (cOR = 2.47, 95% CI = 0.96-6.37) but results were not statistically significant. Increased BPA concentration is associated with an increased risk for PTB or pPROM depending on the maternal-fetal compartment(s) affected. High MP plasma BPA concentrations are associated with PTB with intact membranes but high AF BPA concentrations may weakly be associated with pPROM.

BPA qualtitative and quantitative assessment associated with orthodontic bonding in vivo.

PubMed

Kloukos, Dimitrios; Sifakakis, Iosif; Voutsa, Dimitra; Doulis, Ioannis; Eliades, George; Katsaros, Christos; Eliades, Theodore

2015-08-01

To assess the in vivo amount of BPA released from a visible light-cured orthodontic adhesive, immediately after bracket bonding. 20 orthodontic patients were recruited after obtaining informed consent. All patients received 24 orthodontic brackets in both dental arches. In Group A (11 patients), 25 ml of tap water were used for mouth rinsing, whereas in Group B (9 patients) a simulated mouth rinse formulation was used: a mixture of 20 ml de-ionized water plus 5 ml absolute ethanol. Rinsing solutions were collected before, immediately after placing the orthodontic appliances and after washing out the oral cavity and were then stored in glass tubes. Rinsing was performed in a single phase for 60s with the entire volume of each liquid. The BPA analysis was performed by gas chromatography-mass spectrometry. An increase in BPA concentration immediately after the 1st post-bonding rinse was observed, for both rinsing media, which was reduced after the 2nd post-bonding rinse. Water exhibited higher levels of BPA concentration than water/ethanol after 1st and 2nd post-bonding rinses. Two-way mixed Repeated Measures ANOVA showed that the primary null hypothesis declaring mean BPA concentration to be equal across rinsing medium and rinsing status was rejected (p-value <0.001). The main effects of the rinsing medium and status, as well as their interaction were found to be statistically significant (p-values 0.048, <0.001 and 0.011 respectively). A significant pattern of increase of BPA concentration, followed by a decrease that reached the initial values was observed. The amount of BPA was relatively low and far below the reference limits of tolerable daily intake. Copyright © 2015. Published by Elsevier Ltd.

In Vitro Effects of Bisphenol A β-D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes.

PubMed

Boucher, Jonathan G; Boudreau, Adèle; Ahmed, Shaimaa; Atlas, Ella

2015-12-01

Exposure to common environmental substances, such as bisphenol A (BPA), has been associated with a number of negative health outcomes. In vivo, BPA is rapidly converted to its predominant metabolite, BPA-glucuronide (BPA-G), which has long been believed to be biologically inactive because it lacks estrogenic activity. However, the effects of BPA-G on cellular metabolism have not been characterized. In the present study we examined the effect of BPA-G on adipogenesis. The effect of BPA-G on the differentiation of human and 3T3L1 murine preadipocytes was evaluated in vitro by quantifying lipid accumulation and the expression of adipogenic markers. Treatment of 3T3L1 preadipocytes with 10 μM BPA-G induced a significant increase in lipid accumulation, mRNA expression of the adipogenic markers sterol regulatory element binding factor 1 (SREBF1) and lipoprotein lipase (LPL), and protein levels of LPL, aP2, and adipsin. Treatment of primary human preadipocytes with BPA-G also induced adipogenesis as determined by aP2 levels. Co-treatment of cells with the estrogen receptor (ER) antagonist fulvestrant (ICI) significantly inhibited the BPA-G-induced increase in LPL and aP2 levels, whereas treatment with ICI alone had no effect. Moreover, BPA-G did not display any significant estrogenic activity. To our knowledge, this study is the first to report that BPA-G induces adipocyte differentiation and is not simply an inactive metabolite. The fact that BPA-G induced adipogenesis and was inhibited by an ER antagonist yet showed no estrogenic activity suggests that it has no classical ER transcriptional activation function and acts through a pathway that remains to be determined.

Accelerated biodegradation of BPA in water-sediment microcosms with Bacillus sp. GZB and the associated bacterial community structure.

PubMed

Xiong, Jukun; An, Taicheng; Li, Guiying; Peng, Ping'an

2017-10-01

Bisphenol A (BPA) is a synthetic chemical primarily used to produce polycarbonate plastics and epoxy resins. Significant industrial and consumer's consumption of BPA-containing products has contributed to extensive contamination in different environmental matrices. In this study, microcosms bioaugmented with Bacillus sp. GZB were constructed to investigate BPA biodegradation, identify the main bacterial community, and evaluate bacterial community responses in the microcosms. Under aerobic conditions, BPA was quickly depleted as a result of bioaugmentation with Bacillus sp. GZB in water-sediment contaminated with pollutants. The pollutants used were generally associated with the electronic wastes (mobile phones, computers, televisions) dismantling process. Adding BPA affected the bacterial community composition in the water-sediment. Furthermore, BPA biodegradation was enhanced by adding electron donors/co-substrates: humic acid, NaCl, glucose, and yeast extract. Metagenomic analysis of the total 16S rRNA genes from the BPA-degrading microcosms with bioaugmentation illustrated that the genera Bacillus, Thiobacillus, Phenylobacterium, and Cloacibacterium were dominant after a 7-week incubation period. A consortium of microorganisms from different bacterial genera may be involved in BPA biodegradation in electronic waste contaminated water-sediment. This study provides new insights about BPA bioaugmentation and bacterial ecology in the BPA-degrading environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does BPA alter steroid hormone synthesis in human granulosa cells in vitro?

PubMed

Mansur, Abdallah; Adir, Michal; Yerushalmi, Gil; Hourvitz, Ariel; Gitman, Hila; Yung, Yuval; Orvieto, Raoul; Machtinger, Ronit

2016-07-01

Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro? At supra-physiological concentrations, BPA alters progesterone and estradiol synthesis in vitro and significantly reduces the mRNA and protein expression levels of three genes encoding steroidogenesis enzymes. In IVF patients, the effects of BPA exposure on cycle outcome are controversial. Previous animal studies have shown that granulosa cell steroid hormone synthesis is compromised after BPA exposure, but their findings have been difficult to replicate in humans due, in part, to the low availability of discarded biological material. Luteinized granulosa cells obtained from 44 fertile and infertile patients undergoing in vitro fertilization were cultured for 48 h with different concentrations of BPA (0, 0.2, 0.02, 2.0, 20 µg/ml). Culture medium and total RNA extracted from the luteinized granulosa cells were examined for estradiol and progesterone levels as well as mRNA and protein expression of steroidogenesis enzymes, using enzyme immunoassays, real-time PCR and western blots. Treatment of granulosa cells with 2 or 20 µg/ml BPA for 48 h resulted in significantly lower progesterone biosynthesis (P < 0.005 and <0.001, respectively). Estradiol production was significantly altered only after incubation with 20 µg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17β-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3β-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 µg/ml BPA. Lower BPA concentrations similar to, and up to 100 times, the concentrations measured in human follicular fluid, serum and urine did not alter steroidogenesis in primary granulosa cell cultures. This was an in vitro study investigating the effects of acute exposure (48 h) of BPA on discarded material. As such, the model

In Vitro Effects of Bisphenol A β-D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes

PubMed Central

Boucher, Jonathan G.; Boudreau, Adèle; Ahmed, Shaimaa

2015-01-01

Background Exposure to common environmental substances, such as bisphenol A (BPA), has been associated with a number of negative health outcomes. In vivo, BPA is rapidly converted to its predominant metabolite, BPA-glucuronide (BPA-G), which has long been believed to be biologically inactive because it lacks estrogenic activity. However, the effects of BPA-G on cellular metabolism have not been characterized. In the present study we examined the effect of BPA-G on adipogenesis. Methods The effect of BPA-G on the differentiation of human and 3T3L1 murine preadipocytes was evaluated in vitro by quantifying lipid accumulation and the expression of adipogenic markers. Results Treatment of 3T3L1 preadipocytes with 10 μM BPA-G induced a significant increase in lipid accumulation, mRNA expression of the adipogenic markers sterol regulatory element binding factor 1 (SREBF1) and lipoprotein lipase (LPL), and protein levels of LPL, aP2, and adipsin. Treatment of primary human preadipocytes with BPA-G also induced adipogenesis as determined by aP2 levels. Co-treatment of cells with the estrogen receptor (ER) antagonist fulvestrant (ICI) significantly inhibited the BPA-G–induced increase in LPL and aP2 levels, whereas treatment with ICI alone had no effect. Moreover, BPA-G did not display any significant estrogenic activity. Conclusions To our knowledge, this study is the first to report that BPA-G induces adipocyte differentiation and is not simply an inactive metabolite. The fact that BPA-G induced adipogenesis and was inhibited by an ER antagonist yet showed no estrogenic activity suggests that it has no classical ER transcriptional activation function and acts through a pathway that remains to be determined. Citation Boucher JG, Boudreau A, Ahmed S, Atlas E. 2015. In vitro effects of bisphenol A β-D-glucuronide (BPA-G) on adipogenesis in human and murine preadipocytes. Environ Health Perspect 123:1287–1293; http://dx.doi.org/10.1289/ehp.1409143 PMID:26018136

Exposure of children to BPA through dust and the association of urinary BPA and triclosan with oxidative stress in Guangzhou, China.

PubMed

Lv, Yanshan; Rui, Caiyan; Dai, Yanyan; Pang, Qihua; Li, Yanru; Fan, Ruifang; Lu, Shaoyou

2016-12-08

Both bisphenol A (BPA) and triclosan (TCS) are phenolic compounds widely used in a variety of household applications. These compounds could be released into the environment, enter the human body and cause a series of potential health hazards. Children are sensitive and susceptible to these contaminants. To investigate the potential oxidative DNA damage from exposure to BPA and TCS, ninety six urine samples of children (aged 3-6) and 57 dust samples were collected from a kindergarten in Guangzhou, China. The concentrations of urinary BPA, TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage) in urine were determined using a liquid chromatography tandem mass spectrometer. The geometric mean concentrations of urinary BPA, TCS and 8-OHdG were 1.08 μg L -1 , 1.34 μg L -1 and 1.90 μg L -1 , respectively. The results showed that both BPA and TCS exposures were associated with oxidative damage. Significant dose-effects existed between the urinary BPA, TCS levels and the 8-OHdG concentrations. Multiple linear regression analysis showed that one percent increase in BPA and in TCS could generate 0.15% and 0.081% increase in 8-OHdG in urine for children in Guangzhou. We also determined the concentrations of BPA in dust using high performance liquid chromatography. The mean concentration of BPA was 2.86 μg g -1 in indoor dust and 3.23 μg g -1 in outdoor dust. The dust contributes approximately 9.23% to the urinary BPA exposure for the children. In conclusion, BPA and TCS exposure correlates with oxidative DNA damage.

Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products.

PubMed

Bittner, George D; Yang, Chun Z; Stoner, Matthew A

2014-05-28

Xenobiotic chemicals with estrogenic activity (EA), such as bisphenol A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA. We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor. Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and Tritan™ resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested. This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of EA, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC

Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases.

PubMed

Trivillin, V A; Garabalino, M A; Colombo, L L; González, S J; Farías, R O; Monti Hughes, A; Pozzi, E C C; Bortolussi, S; Altieri, S; Itoiz, M E; Aromando, R F; Nigg, D W; Schwint, A E

2014-06-01

BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25-76ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung. © 2013 Published by Elsevier Ltd.

Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

D.W. Nigg; Various Others

BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.

Effects of developmental exposure to bisphenol A on spatial navigational learning and memory in rats: A CLARITY-BPA study.

PubMed

Johnson, Sarah A; Javurek, Angela B; Painter, Michele S; Ellersieck, Mark R; Welsh, Thomas H; Camacho, Luísa; Lewis, Sherry M; Vanlandingham, Michelle M; Ferguson, Sherry A; Rosenfeld, Cheryl S

2016-04-01

Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a wide variety of items. Previous studies suggest BPA exposure may result in neuro-disruptive effects; however, data are inconsistent across animal and human studies. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats developmentally exposed to BPA demonstrated later spatial navigational learning and memory deficits. Pregnant NCTR Sprague-Dawley rats were orally dosed from gestational day 6 to parturition, and offspring were directly orally dosed until weaning (postnatal day 21). Treatment groups included a vehicle control, three BPA doses (2.5μg/kg body weight (bw)/day-[2.5], 25μg/kg bw/day-[25], and 2500μg/kg bw/day-[2500]) and a 0.5μg/kg/day ethinyl estradiol (EE)-reference estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than control females to locate the escape box in the allotted time (p value=0.04). Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach significance (p value=0.06), whereas 2.5 BPA males showed improved latency compared to control males (p value=0.04), although the significance of this result is uncertain. No differences in serum testosterone concentration were detected in any male or female treatment groups. Current findings suggest developmental exposure of rats to BPA may disrupt aspects of spatial navigational learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Developmental Exposure to Bisphenol A on Spatial Navigational Learning and Memory in Rats: A CLARITY-BPA Study

PubMed Central

Johnson, Sarah A.; Javurek, Angela B.; Painter, Michele S.; Ellersieck, Mark R.; Welsh, Thomas H.; Camacho, Luísa; Lewis, Sherry M.; Vanlandingham, Michelle M.; Ferguson, Sherry A.; Rosenfeld, Cheryl S.

2015-01-01

Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a wide variety of items. Previous studies suggest BPA exposure may result in neuro-disruptive effects; however, data are inconsistent across animal and human studies. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats developmentally exposed to BPA demonstrated later spatial navigational learning and memory deficits. Pregnant NCTR Sprague-Dawley rats were orally dosed from gestational day 6 to parturition, and offspring were directly orally dosed until weaning (postnatal day 21). Treatment groups included a vehicle control, three BPA doses (2.5 μg/kg/day-[2.5], 25 μg/kg/day-[25], and 2500 μg/kg/day-[2500]) and a 0.5 μg/kg/day ethinyl estradiol (EE)-reference estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than control females to locate the escape box in the allotted time (P value= 0.04). Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach significance (P value = 0.06), whereas 2.5 BPA males showed improved latency compared to control males (P value = 0.04), although the significance of this result is uncertain. No differences in serum testosterone concentration were detected in any male or female treatment groups. Current findings suggest developmental exposure of rats to BPA may disrupt aspects of spatial navigational learning and memory. PMID:26436835

Degradation and mineralization of Bisphenol A (BPA) in aqueous solution using advanced oxidation processes: UV/H2O2 and UV/S2O8(2-) oxidation systems.

PubMed

Sharma, Jyoti; Mishra, I M; Kumar, Vineet

2015-06-01

This work reports on the removal and mineralization of an endocrine disrupting chemical, Bisphenol A (BPA) at a concentration of 0.22 mM in aqueous solution using inorganic oxidants (hydrogen peroxide, H2O2 and sodium persulfate, Na2S2O8;S2O8(2-)) under UV irradiation at a wavelength of 254 nm and 40 W power (Io = 1.26 × 10(-6) E s(-1)) at its natural pH and a temperature of 29 ± 3 °C. With an optimum persulfate concentration of 1.26 mM, the UV/S2O8(2-) process resulted in ∼95% BPA removal after 240 min of irradiation. The optimum BPA removal was found to be ∼85% with a H2O2 concentration of 11.76 mM. At higher concentrations, either of the oxidants showed an adverse effect because of the quenching of the hydroxyl or sulfate radicals in the BPA solution. The sulfate-based oxidation process could be used over a wider initial pH range of 3-12, but the hydroxyl radical-based oxidation of BPA should be carried out in the acidic pH range only. The water matrix components (bicarbonate, chloride and humic acid) showed higher scavenging effect in hydroxyl radical-based oxidation than that in the sulfate radical-based oxidation of BPA. UV/S2O8(2-) oxidation system utilized less energy (307 kWh/m(3)) EE/O in comparison to UV/H2O2 system (509 kWh/m(3)) under optimum operating conditions. The cost of UV irradiation far outweighed the cost of the oxidants in the process. However, the total cost of treatment of persulfate-based system was much lower than that of H2O2-based oxidation system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta)

USGS Publications Warehouse

Jandegian, Caitlin M.; Deem, Sharon L.; Bhandari, Ramji K.; Holliday, Casey M.; Nicks, Diane; Rosenfeld, Cheryl S.; Selcer, Kyle; Tillitt, Donald E.; vom Saal, Fredrick S.; Velez, Vanessa; Yang, Ying; Holliday, Dawn K.

2015-01-01

Environmental chemicals can disrupt endocrine signaling and adversely impact sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical commonly found in a variety of habitats. In this study, we used painted turtles (Chrysemys picta), which have temperature-dependent sex determination (TSD), as an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that BPA would override TSD and disrupt sexual development. We incubated farm-raised turtle eggs at the male-producing temperature (26 °C), randomly assigned individuals to treatment groups: control, vehicle control, 17β-estradiol (E2, 20 ng/g-egg) or 0.01, 1.0, 100 μg BPA/g-egg and harvested tissues at hatch. Typical female gonads were present in 89% of the E2-treated “males”, but in none of the control males (n = 35). Gonads of BPA-exposed turtles had varying amounts of ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the medulla. Although the percentage of males with OLCs increased with BPA dose (BPA-low = 30%, BPA-medium = 33%, BPA-high = 39%), this difference was not significant (p = 0.85). In all three BPA treatments, SOX9 patterns revealed disorganized medullary testicular tubules and β-catenin expression in a thickened cortex. Liver vitellogenin, a female-specific liver protein commonly used as an exposure biomarker, was not induced by any of the treatments. Notably, these results suggest that developmental exposure to BPA disrupts sexual differentiation in painted turtles. Further examination is necessary to determine the underlying mechanisms of sex reversal in reptiles and how these translate to EDC exposure in wild populations.

Air, hand wipe, and surface wipe sampling for Bisphenol A (BPA) among workers in industries that manufacture and use BPA in the United States.

PubMed

Hines, Cynthia J; Jackson, Matthew V; Christianson, Annette L; Clark, John C; Arnold, James E; Pretty, Jack R; Deddens, James A

2017-11-01

For decades, bisphenol A (BPA) has been used in making polycarbonate, epoxy, and phenolic resins and certain investment casting waxes, yet published exposure data are lacking for U.S. manufacturing workers. In 2013-2014, BPA air and hand exposures were quantified for 78 workers at six U.S. companies making BPA or BPA-based products. Exposure measures included an inhalable-fraction personal air sample on each of two consecutive work days (n = 146), pre- and end-shift hand wipe samples on the second day (n = 74 each), and surface wipe samples (n = 88). Potential determinants of BPA air and end-shift hand exposures (after natural log transformation) were assessed in univariate and multiple regression mixed models. The geometric mean (GM) BPA air concentration was 4.0 µg/m 3 (maximum 920 µg/m 3 ). The end-shift GM BPA hand level (26 µg/sample) was 10-times higher than the pre-shift level (2.6 µg/sample). BPA air and hand exposures differed significantly by industry and job. BPA air concentrations and end-shift hand levels were highest in the BPA-filled wax manufacturing/reclaim industry (GM Air = 48 µg/m 3 , GM Hand-End = 130 µg/sample) and in the job of working with molten BPA-filled wax (GM Air = 43 µg/m 3 , GM Hand-End = 180 µg/sample), and lowest in the phenolic resins industry (GM Air = 0.85 µg/m 3 , GM Hand-End = 0.43 µg/sample) and in the job of flaking phenolic resins (GM AIR = 0.62 µg/m 3 , GM Hand-End = 0.38 µg/sample). Determinants of increased BPA air concentration were industry, handling BPA containers, spilling BPA, and spending ≥50% of the shift in production areas; increasing age was associated with lower air concentrations. BPA hand exposure determinants were influenced by high values for two workers; for all other workers, tasks involving contact with BPA-containing materials and spending ≥50% of the shift in production areas were associated with increased BPA hand levels. Surface wipe BPA levels were significantly lower in

Late pregnancy is vulnerable period for exposure to BPA.

PubMed

Ohtani, Naoko; Suda, Koshi; Tsuji, Erika; Tanemura, Kentaro; Yokota, Hiroshi; Inoue, Hiroki; Iwano, Hidetomo

2018-03-30

Bisphenol A (BPA) is among the better-known endocrine disruptors. BPA is used in various food-contacting materials and is easily eluted into food; as a result, we are exposed to BPA on a daily basis. In adults, BPA is metabolized and eliminated rapidly from the body. However, numerous reports suggest that fetuses and young children are susceptible to BPA. One of the concerning adverse effects of BPA is disruption of behavior, especially anxiety-like behavior. In order to study the mechanism of influences on offspring, it is important to clarify the most vulnerable gestation period. We hypothesized that offspring in late pregnancy would be more susceptible to BPA, because late pregnancy is a critical time for functional brain development. In this study, C57BL/6 mouse fetuses were exposed prenatally by oral dosing of pregnant dams, once daily from gestational day 5.5 to 12.5 (early pregnancy) or 11.5 to 18.5 (late pregnancy), with BPA (0 or 10 mg/kg body weight). Following birth and weaning, the resulting pups were tested using an elevated plus maze at postnatal week 10. The behavior of the offspring was altered by prenatal BPA exposure during late pregnancy but not during early pregnancy. These results indicated that offspring are more vulnerable to exposure to BPA in late pregnancy.

Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products

PubMed Central

2014-01-01

Background Xenobiotic chemicals with estrogenic activity (EA), such as bisphenol A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA. Methods We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor. Results Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and Tritan™ resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested. Conclusions This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of EA, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at

Bisphenol A (BPA) the mighty and the mutagenic.

PubMed

Jalal, Nasir; Surendranath, Austin R; Pathak, Janak L; Yu, Shi; Chung, Chang Y

2018-01-01

Bisphenol A (BPA) is one of the most widely used synthetic compounds on the planet. Upon entering the diet, its highest concentration (1-104 ng/g of tissue) has been recorded in the placenta and fetus. This accumulation of BPA can have many health hazards ranging from the easy to repair single strand DNA breaks (SSBs) to error prone double strand DNA breaks (DSBs). Although the Human liver can efficiently metabolize BPA via glucuronidation and sulfation pathways, however the by-product Bisphenol -o- quinone has been shown to act as a DNA adduct. Low doses of BPA have also been shown to interact with various signaling pathways to disrupt normal downstream signaling. Analysis has been made on how BPA could interact with several signaling pathways such as NFκB, JNK, MAPK, ER and AR that eventually lead to disease morphology and even tumorigenesis. The role of low dose BPA is also discussed in dysregulating Ca 2+ homeostasis of the cell by inhibiting calcium channels such as SPCA1/2 to suggest a new direction for future research in the realms of BPA induced disease morphology and mutagenicity.

Inter-Sectoral Bisphenol A (BPA) Flows in the 2012 Chinese Economy.

PubMed

Jiang, Daqian; Chen, Wei-Qiang; Liu, Wei; Chertow, Marian

2017-08-01

Bisphenol A (BPA), a widely used petrochemical compound, has become an emerging global environmental management challenge because its leakage is associated with potential environmental and human health impacts. Until now, available BPA statistics have been limited to the products that directly use BPA. In this study, we delineate direct and indirect BPA flows for the 2012 Chinese economy. We find that construction, production of educational and recreational products, and automobile manufacturing are the most BPA-intensive sectors in terms of total BPA flows (300, 157, and 130 Gg total BPA flows, respectively). The public management and health sectors, however, incur significant indirect BPA flows, defined as embedded and inter-sectoral BPA placed into use, even though direct BPA use by these sectors is limited. By revealing the currently overlooked indirect BPA flows, this study reveals data gaps that are highly relevant to improving the accuracy of estimated BPA flows and losses. The method used herein is transferrable to other emerging and environmentally relevant materials, thereby providing the holistic understanding needed for cities, regions, or nations to design effective policy interventions.

Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

PubMed

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

PubMed Central

HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

2015-01-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

Sustainability at BPA 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

THIS IS THE THIRD YEAR BPA has reported on sustainability program accomplishments. The report provides an opportunity to review progress made on sustainability initiatives, evaluate how far we have come and how much we can improve. The program has demonstrated maturation as the concepts of sustainability and resource conservation are communicated and understood. The sustainability program started as an employee-driven “grass roots” effort in 2010. Sustainability is becoming a consideration in how work is performed. The establishment of several policies supporting sustainability efforts proves the positive progress being made. In 2009, BPA became a founder and member of The Climatemore » Registry, a nonprofit collaboration that sets standards to calculate, verify and report greenhouse gas emissions. This year, BPA completed and published our Greenhouse Gas inventory for the years of 2009, 2010 and 2011. The 2012 inventory is currently in the process of third-party verification and scheduled for public release in January 2014. These inventories provide a concrete measure of the progress we are making.« less

Environmental Effects of BPA

PubMed Central

Canesi, Laura

2015-01-01

Research on bisphenol A (BPA) as an environmental contaminant has now major regulatory implications toward the ecosystem health, and hence it is incumbent on scientists to do their research to the highest standards possible, in order that the most appropriate decisions are made to mitigate the impacts to aquatic wildlife. However, the contribution given so far appears rather fragmented. The present overview aims to collect available information on the effects of BPA on aquatic vertebrates and invertebrates to provide a general scenario and to suggest future developments toward more comprehensive approaches useful for aquatic species protection. PMID:26674307

Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study

PubMed Central

Arambula, Sheryl E.; Belcher, Scott M.; Planchart, Antonio; Turner, Stephen D.

2016-01-01

Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the no-observed-adverse-effect level can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the Consortium Linking Academic and Regulatory Insights of BPA Toxicity program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0-, 2.5-, 25-, 250-, 2500-, or 25 000-μg/kg body weight [bw]/d). Ethinyl estradiol was used as a reference estrogen (0.05- or 0.5-μg/kg bw/d). Postnatal day 1 brains were microdissected and gene expression was assessed with RNA-sequencing (0-, 2.5-, and 2500-μg/kg bw BPA groups only) and/or quantitative real-time PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ERα and ERβ (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current no-observed-adverse-effect level, can alter gene expression in the developing brain. PMID:27571134

Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study.

PubMed

Arambula, Sheryl E; Belcher, Scott M; Planchart, Antonio; Turner, Stephen D; Patisaul, Heather B

2016-10-01

Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the no-observed-adverse-effect level can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the Consortium Linking Academic and Regulatory Insights of BPA Toxicity program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0-, 2.5-, 25-, 250-, 2500-, or 25 000-μg/kg body weight [bw]/d). Ethinyl estradiol was used as a reference estrogen (0.05- or 0.5-μg/kg bw/d). Postnatal day 1 brains were microdissected and gene expression was assessed with RNA-sequencing (0-, 2.5-, and 2500-μg/kg bw BPA groups only) and/or quantitative real-time PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ERα and ERβ (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current no-observed-adverse-effect level, can alter gene expression in the developing brain.

Occupational exposure to bisphenol A (BPA) in a plastic injection molding factory in Malaysia.

PubMed

Kouidhi, Wided; Thannimalay, Letchumi; Soon, Chen Sau; Ali Mohd, Mustafa

2017-07-14

The purpose of this study has been to assess ambient bisphenol A (BPA) levels in workplaces and urine levels of workers and to establish a BPA database for different populations in Malaysia. Urine samples were collected from plastic factory workers and from control subjects after their shift. Air samples were collected using gas analyzers from 5 sampling positions in the injection molding unit work area and from ambient air. The level of BPA in airborne and urine samples was quantified by the gas chromatography mass spectrometry - selected ion monitoring (GCMS-SIM) analysis. Bisphenol A was detected in the median range of 8-28.3 ng/m³ and 2.4-3.59 ng/m³ for the 5 sampling points in the plastic molding factory and in the ambient air respectively. The median urinary BPA concentration was significantly higher in the workers (3.81 ng/ml) than in control subjects (0.73 ng/ml). The urinary BPA concentration was significantly associated with airborne BPA levels (ρ = 0.55, p < 0.01). Our findings provide the first evidence that workers in a molding factory in Malaysia are occupationally exposed to BPA. Int J Occup Med Environ Health 2017;30(5):743-750. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection.

PubMed

Zimmerman, Shawn M; Michel, Frank; Hogan, Robert J; Lafontaine, Eric R

2015-01-01

Burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. Previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of Gram-negative bacteria. In the present study, we report the characterization of one of these autotransporters, BpaB. Database searches identified the bpaB gene in ten B. mallei isolates and the predicted proteins were 99-100% identical. Comparative sequence analyses indicate that the gene product is a trimeric autotransporter of 1,090 amino acids with a predicted molecular weight of 105-kDa. Consistent with this finding, we discovered that recombinant bacteria expressing bpaB produce a protein of ≥ 300-kDa on their surface that is reactive with a BpaB-specific monoclonal antibody. Analysis of sera from mice infected with B. mallei indicated that animals produce antibodies against BpaB during the course of disease, thus establishing production of the autotransporter in vivo. To gain insight on its role in virulence, we inactivated the bpaB gene of B. mallei strain ATCC 23344 and determined the median lethal dose of the mutant in a mouse model of aerosol infection. These experiments revealed that the bpaB mutation attenuates virulence 8-14 fold. Using a crystal violet-based assay, we also discovered that constitutive production of BpaB on the surface of B. mallei promotes biofilm formation. To our knowledge, this is the first report of a biofilm factor for this organism.

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection

PubMed Central

Zimmerman, Shawn M.; Michel, Frank

2015-01-01

Burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. Previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of Gram-negative bacteria. In the present study, we report the characterization of one of these autotransporters, BpaB. Database searches identified the bpaB gene in ten B. mallei isolates and the predicted proteins were 99-100% identical. Comparative sequence analyses indicate that the gene product is a trimeric autotransporter of 1,090 amino acids with a predicted molecular weight of 105-kDa. Consistent with this finding, we discovered that recombinant bacteria expressing bpaB produce a protein of ≥300-kDa on their surface that is reactive with a BpaB-specific monoclonal antibody. Analysis of sera from mice infected with B. mallei indicated that animals produce antibodies against BpaB during the course of disease, thus establishing production of the autotransporter in vivo. To gain insight on its role in virulence, we inactivated the bpaB gene of B. mallei strain ATCC 23344 and determined the median lethal dose of the mutant in a mouse model of aerosol infection. These experiments revealed that the bpaB mutation attenuates virulence 8-14 fold. Using a crystal violet-based assay, we also discovered that constitutive production of BpaB on the surface of B. mallei promotes biofilm formation. To our knowledge, this is the first report of a biofilm factor for this organism. PMID:25993100

Prenatal bisphenol A (BPA) exposure alters the transcriptome of the neonate rat amygdala in a sex-specific manner: a CLARITY-BPA consortium study.

PubMed

Arambula, Sheryl E; Jima, Dereje; Patisaul, Heather B

2018-03-01

Bisphenol A (BPA) is a widely recognized endocrine disruptor prevalent in many household items. Because experimental and epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, even at levels below the current US FDA No Observed Adverse Effect Level (NOAEL) of 5mg/kg body weight (bw)/day, there is concern that early life exposure may alter neurodevelopment. The current study was conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program and examined the full amygdalar transcriptome on postnatal day (PND) 1, with the hypothesis that prenatal BPA exposure would alter the expression of genes and pathways fundamental to sex-specific affective behaviors. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (2.5, 25, 250, 2500, or 25000μg/kg bw/day), a reference estrogen (0.05 or 0.5μg ethinyl estradiol (EE 2 )/kg bw/day), or vehicle. PND 1 amygdalae were microdissected and gene expression was assessed with qRT-PCR (all exposure groups) and RNAseq (vehicle, 25 and 250μg BPA, and 0.5μg EE 2 groups only). Our results demonstrate that that prenatal BPA exposure can disrupt the transcriptome of the neonate amygdala, at doses below the FDA NOAEL, in a sex-specific manner and indicate that the female amygdala may be more sensitive to BPA exposure during fetal development. We also provide additional evidence that developmental BPA exposure can interfere with estrogen, oxytocin, and vasopressin signaling pathways in the developing brain and alter signaling pathways critical for synaptic organization and transmission. Copyright © 2017 Elsevier B.V. All rights reserved.

Presence and leaching of bisphenol a (BPA) from dental materials

PubMed Central

Becher, Rune; Wellendorf, Hanne; Sakhi, Amrit Kaur; Samuelsen, Jan Tore; Thomsen, Cathrine; Bølling, Anette Kocbach; Kopperud, Hilde Molvig

2018-01-01

Abstract BPA has been reported to leach from some resin based dental restorative materials and materials used for orthodontic treatment. To confirm and update previous findings, especially in light of the new temporary lower threshold value for tolerable daily BPA intake, we have investigated the leaching of BPA from 4 composite filling materials, 3 sealants and 2 orthodontic bonding materials. The materials were either uncured and dissolved in methanol or cured. The cured materials were kept in deionized water for 24 hours or 2 weeks. Samples were subsequently analyzed by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS-MS). The composite filling material Tetric EvoFlow® and the fissure sealant DELTON® showed significantly higher levels of BPA leaching compared to control samples for all test conditions (uncured, 24 h leaching and 2 weeks leaching). There were no significant differences in amount of leached BPA for any of the tested materials after 24 hours compared to 2 weeks. These results show that BPA is still released from some dental materials despite the general concern about potential adverse effects of BPA. However, the amounts of BPA were relatively low and most likely represent a very small contribution to the total BPA exposure. PMID:29868625

Presence and leaching of bisphenol a (BPA) from dental materials.

PubMed

Becher, Rune; Wellendorf, Hanne; Sakhi, Amrit Kaur; Samuelsen, Jan Tore; Thomsen, Cathrine; Bølling, Anette Kocbach; Kopperud, Hilde Molvig

2018-01-01

BPA has been reported to leach from some resin based dental restorative materials and materials used for orthodontic treatment. To confirm and update previous findings, especially in light of the new temporary lower threshold value for tolerable daily BPA intake, we have investigated the leaching of BPA from 4 composite filling materials, 3 sealants and 2 orthodontic bonding materials. The materials were either uncured and dissolved in methanol or cured. The cured materials were kept in deionized water for 24 hours or 2 weeks. Samples were subsequently analyzed by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS-MS). The composite filling material Tetric EvoFlow ® and the fissure sealant DELTON ® showed significantly higher levels of BPA leaching compared to control samples for all test conditions (uncured, 24 h leaching and 2 weeks leaching). There were no significant differences in amount of leached BPA for any of the tested materials after 24 hours compared to 2 weeks. These results show that BPA is still released from some dental materials despite the general concern about potential adverse effects of BPA. However, the amounts of BPA were relatively low and most likely represent a very small contribution to the total BPA exposure.

Simultaneous adsorption of Cd²⁺ and BPA on amphoteric surfactant activated montmorillonite.

PubMed

Liu, Chongmin; Wu, Pingxiao; Zhu, Yajie; Tran, Lytuong

2016-02-01

The study mainly investigated the simultaneous adsorption of bisphenol A (BPA) and Cd(2+) from aqueous solution on octadecane-betaine modified montmorillonite (BS-Mt). The characteristics of the obtained materials were analyzed by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), Specific surface area (BET) and Scanning electron microscopy/Energy disperse spectroscopy (SEM/EDS), confirming that BS-18 was successfully introduced into Mt. Also, factors including initial solution pH, initial Cd(2+)/BPA concentration, contact time and adsorbent dosage on the adsorption processes were shown to be crucial for Cd(2+) adsorption, whereas had negligible effects on BPA adsorption. In this study, we found that pseudo-second-order model fitted well with the adsorption kinetic studies for both Cd(2+) and BPA with an equilibrium time of 24 h. The Cd(2+) and BPA adsorption isotherm could be well described by Freundlich model and Langmuir model, respectively. On the basis of kinetic models, the maximum adsorption capacity of Cd(2+) in aqueous solution was slightly enhanced after modification, indicating that Cd(2+) adsorption on BS-Mt was mainly attributed to direct electrostatic attraction and the chelate reaction, while the dramatic enhancement of maximum adsorption capacity for BPA was due to the hydrophobic interaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA.

PubMed

Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

2017-10-01

To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Removal of bisphenol A (BPA) in a nitrifying system with immobilized biomass.

PubMed

Zielińska, Magdalena; Cydzik-Kwiatkowska, Agnieszka; Bernat, Katarzyna; Bułkowska, Katarzyna; Wojnowska-Baryła, Irena

2014-11-01

The potential for bisphenol A (BPA) removal by mixed consortia of immobilized microorganisms with high nitrification activity was investigated with BPA concentrations in the influent from 2.5 to 10.0 mg/L. The presence of BPA limited ammonium oxidation; nitrification efficiency decreased from 91.2±1.3% in the control series to 47.4±9.4% when BPA concentration in wastewater was the highest. The efficiency of BPA removal rose from 87.1±5.5% to 92.9±2.9% with increased BPA concentration in the influent. Measurement of oxygen uptake rates by biomass exposed to BPA showed that BPA was mainly removed by heterotrophic bacteria. A strong negative correlation between the BPA removal efficiency and nitrification efficiency indicated the limited contribution of ammonia-oxidizing bacteria (AOB) to BPA biodegradation. Exposure of biomass to BPA changed the quantity and diversity of AOB in the biomass as shown by real-time PCR and denaturing gradient gel electrophoresis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamic Stocks and Flows Analysis of Bisphenol A (BPA) in China: 2000-2014.

PubMed

Jiang, Daqian; Chen, Wei-Qiang; Zeng, Xianlai; Tang, Linbin

2018-03-20

Bisphenol A (BPA), a synthetic organic chemical, is creating a new category of ecological and human health challenges due to unintended leakage. Effectively managing the use and leakage of BPA can benefit from an understanding of the anthropogenic BPA cycles (i.e., the size of BPA flows and stocks). In this work, we provide a dynamic analysis of the anthropogenic BPA cycles in China for 2000-2014. We find that China's BPA consumption has increased 10-fold since 2000, to ∼3 million tonnes/year. With the increasing consumption, China's in-use BPA stock has increased 500-fold to 14.0 million tonnes (i.e., 10.2 kg BPA/capita). It is unclear whether a saturation point has been reached, but in 2004-2014, China's in-use BPA stock has been increasing by 0.8 kg BPA/capita annually. Electronic products are the biggest contributor, responsible for roughly one-third of China's in-use BPA stock. Optical media (DVD/VCD/CDs) is the largest contributor to China's current End-of-Life (EoL) BPA flow, totaling 0.9 million tonnes/year. However, the EoL BPA flow due to e-waste will increase quickly, and will soon become the largest EoL BPA flow. The changing quantities and sources of EoL BPA flows may require a shift in the macroscopic BPA management strategies.

Low concentration of BPA induces mice spermatocytes apoptosis via GPR30.

PubMed

Wang, Chaoliang; Zhang, Jianxiang; Li, Qi; Zhang, Tianbiao; Deng, Zishi; Lian, Jing; Jia, Donghui; Li, Rui; Zheng, Tao; Ding, Xiaoju; Yang, Fan; Ma, Chao; Wang, Rui; Zhang, Weixing; Guo Wen, Jian

2017-07-25

Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be identified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor β (ERβ) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make sure which receptor is responsible for the biological function of BPA, we used ER down-regulator ICI and indicated that BPA could bind to GPR30. We also observed that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that this process was mediated by GPR30-related EGFR-MAPK pathway using western blot. By Real-time PCR, we found that the expression of c-Fos was up-regulated and Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of MTT assay, comet assay and flow cytometry indicated that the activation of GPR30 induced by BPA inhibited the cell growth and induced cell apoptosis and ICI, GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse this effect. Immunohistochemistry on the testis of BPA -damaged mice showed that BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.

[Research on characteristic of interrelationship between toxic organic compound BPA and Chlorella vulgaris].

PubMed

Chen, Shan-Jia; Chen, Xiu-Rong; Yan, Long; Zhao, Jian-Guo; Zhang, Fei; Jiang, Zi-Jian

2014-04-01

The effects of different concentrations of bisphenol A (BPA) on Chlorella vulgaris and removal capacity of BPA by Chlorella vulgaris were investigated. Results showed that a low concentration (0-20 mg x L(-1)) of BPA promoted the growth of Chlorella vulgaris, whereas a relative high concentration (20-50 mg x L(-1)) of BPA inhibited the growth of Chlorella vulgaris, and the inhibition effect was positively correlated with the concentration of BPA. Likewise, a high dose of initial BPA (> 20 mg x L(-1)) led to a decline in the content of chlorephyll a. Chlorella vulgaris had BPA removal capacity when initial BPA concentration ranged from 2 mg x L(-1) to 50 mg x L(-1). There was positive correlation between the removal rate of BPA per cell and initial BPA concentration. The removal rate of BPA was the highest when initial BPA was 50 mg x L(-1), which appeared between lag phase and logarithmic phase.

Mechanistic study of photo-oxidation of Bisphenol-A (BPA) with hydrogen peroxide (H2O2) and sodium persulfate (SPS).

PubMed

Sharma, Jyoti; Mishra, I M; Kumar, Vineet

2016-01-15

The removal of Bisphenol-A (BPA) from contaminated water using advanced oxidation methods such as UV-C assisted oxidation by hydrogen peroxide (H2O2) and sodium persulfate (SPS) has been reported by the authors earlier (Sharma et al., 2015a). In the present study, the authors report the removal of BPA from aqueous solution by the above two methods and its degradation mechanism. UV-C light (254 nm wavelength, 40 W power) was applied to BPA contaminated water at natural pH (pHN) under room temperature conditions. Experiments were carried out with the initial BPA concentration in the range of 0.04 mM-0.31 mM and the oxidant/BPA molar ratio in the range of 294:1-38:1 for UV-C/H2O2 and 31.5-4.06:1 for UV-C/SPS systems. The removal of BPA enhanced with decreasing BPA concentration. The total organic carbon also decreased with the UV-C irradiation time under optimum conditions ([H2O2]0 = 11.76 mM; [SPS]0 = 1.26 mM; temperature (29 ± 3 °C). Competition of BPA for reaction with HO or [Formula: see text] radicals at its higher concentrations results in a decrease in the removal of BPA. The intermediates with smaller and higher molecular weights than that of BPA were found in the treated water. Based on GC-MS and FTIR spectra of the reaction mixture, the formation of hydroxylated by-products testified the HO mediated oxidation pathway in the BPA degradation, while the formation of quinones and phenoxy phenols pointed to the [Formula: see text] dominating pathway through the formation of hydroxycyclohexadienyl (HCHD) and BPA phenoxyl radicals. The main route of BPA degradation is the hydroxylation followed by dehydration, coupling and ring opening reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan

Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60more » mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.« less

A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

PubMed

Williams, K P; Shoelson, S E

1993-03-15

Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

“Stockpile” of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells

PubMed Central

Porreca, Immacolata; Ulloa Severino, Luisa; D’Angelo, Fulvio; Cuomo, Danila; Ceccarelli, Michele; Altucci, Lucia; Amendola, Elena; Nebbioso, Angela; Mallardo, Massimo

2016-01-01

Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity. PMID:26982218

A round robin approach to the analysis of bisphenol a (BPA) in human blood samples

PubMed Central

2014-01-01

Background Human exposure to bisphenol A (BPA) is ubiquitous, yet there are concerns about whether BPA can be measured in human blood. This Round Robin was designed to address this concern through three goals: 1) to identify collection materials, reagents and detection apparatuses that do not contribute BPA to serum; 2) to identify sensitive and precise methods to accurately measure unconjugated BPA (uBPA) and BPA-glucuronide (BPA-G), a metabolite, in serum; and 3) to evaluate whether inadvertent hydrolysis of BPA-G occurs during sample handling and processing. Methods Four laboratories participated in this Round Robin. Laboratories screened materials to identify BPA contamination in collection and analysis materials. Serum was spiked with concentrations of uBPA and/or BPA-G ranging from 0.09-19.5 (uBPA) and 0.5-32 (BPA-G) ng/mL. Additional samples were preserved unspiked as ‘environmental’ samples. Blinded samples were provided to laboratories that used LC/MSMS to simultaneously quantify uBPA and BPA-G. To determine whether inadvertent hydrolysis of BPA metabolites occurred, samples spiked with only BPA-G were analyzed for the presence of uBPA. Finally, three laboratories compared direct and indirect methods of quantifying BPA-G. Results We identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all laboratories were able to distinguish low from high values of uBPA and BPA-G, for the whole spiked sample range and for those samples spiked with the three lowest concentrations (0.5-3.1 ng/ml). By completion of the Round Robin, three laboratories had verified methods for the analysis of uBPA and two verified for the analysis of BPA-G (verification determined by: 4 of 5 samples within 20% of spiked concentrations). In the analysis of BPA-G only spiked samples, all laboratories reported BPA-G was the majority of BPA detected (92.2 – 100%). Finally, laboratories were more likely to be verified

Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.

PubMed

Morales, Mónica; Martínez-Paz, Pedro; Sánchez-Argüello, Paloma; Morcillo, Gloria; Martínez-Guitarte, José Luis

2018-05-15

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study

PubMed Central

Rebuli, Meghan E.; Camacho, Luísa; Adonay, Maria E.; Reif, David M.; Aylor, David L.; Patisaul, Heather B.

2015-01-01

Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats. PMID:26209558

On the applicability of [18F]FBPA to predict L-BPA concentration after amino acid preloading in HuH-7 liver tumor model and the implication for liver boron neutron capture therapy.

PubMed

Grunewald, Catrin; Sauberer, Michael; Filip, Thomas; Wanek, Thomas; Stanek, Johann; Mairinger, Severin; Rollet, Sofia; Kudejova, Petra; Langer, Oliver; Schütz, Christian; Blaickner, Matthias; Kuntner, Claudia

2017-01-01

In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a 10 B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [ 18 F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [ 10 B]L-BPA. Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [ 18 F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injected with [ 10 B]L-BPA with tissue samples analyzed by prompt gamma activation analysis (PGAA) or quantitative neutron capture radiography (QNCR). The impact of L-tyrosine, L-DOPA and L-BPA preloading on the tissue distribution of [ 18 F]FBPA and [ 10 B]L-BPA was evaluated and the pharmacokinetics of [ 18 F]FBPA investigated by compartment modeling. We found a significant correlation between [ 18 F]FBPA and [ 10 B]L-BPA uptake in tumors and various organs as well as high accumulation levels in pancreas and kidneys as reported in previous studies. Tumor-to-liver ratios of [ 18 F]FBPA ranged from 1.2 to 1.5. Preloading did not increase the uptake of [ 18 F]FBPA or [ 10 B]L-BPA in any organ and compartment modeling showed no statistically significant differences in [ 18 F]FBPA tumor kinetics. [ 18 F]FBPA-PET predicts [ 10 B]L-BPA concentration after amino acid preloading in HuH-7 hepatocellular carcinoma models. Preloading had no effect on tumor uptake of [ 18 F]FBPA. Despite differences in chemical structure and administered dose [ 18 F]FBPA and [ 10 B]L-BPA demonstrate an equivalent biodistribution in a preclinical tumor model. IMPLICATIONS FOR PATIENT CARE: [ 18 F]FBPA-PET is suitable for treatment planning and dose calculations in BNCT applications for liver malignancies. However, alternative tracers with more

Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study.

PubMed

Rebuli, Meghan E; Camacho, Luísa; Adonay, Maria E; Reif, David M; Aylor, David L; Patisaul, Heather B

2015-12-01

Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

BPA-toxicity via superoxide anion overload and a deficit in β-catenin signaling in human bone mesenchymal stem cells.

PubMed

Leem, Yea-Hyun; Oh, Seikwan; Kang, Hong-Je; Kim, Jung-Hwa; Yoon, Juno; Chang, Jae-Suk

2017-01-01

Bisphenol A (BPA), used in the manufacture of products based on polycarbonate plastics and epoxy resins, is well known as an endocrine-disrupting monomer. In the current study, BPA increased cytotoxicity in hBMSCs in a dose- and time-dependent manner, concomitantly with increased lipid peroxidation. Increased cell death in BPA-treated cells was markedly blocked by pretreatment with the superoxide dismutase mimetic MnTBAP and MnTMPyP, but not by catalase, glutathione, the glutathione peroxidase mimetic ebselen, the NOS inhibitor NAME, or the xanthine oxidase inhibitor allopurinol. Furthermore, the decline in nuclear β-catenin and cyclin D1 levels in hBMSCs exposed to BPA was reversed by MnTBAP treatment. Finally, treatment of hBMSCs with the GSK3β inhibitor LiCl 2 increased nuclear β-catenin levels and significantly attenuated cytotoxicity compared with BPA treatment. Our current results in hBMSCs exposed to BPA suggest that BPA causes a disturbance in β-catenin signaling via a superoxide anion overload. © 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 32: 344-352, 2017. © 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc.

Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure

PubMed Central

vom Saal, Frederick S.; Welshons, Wade V.

2016-01-01

There is extensive evidence that bisphenol A (BPA) is related to a wide range of adverse health effects based on both human and experimental animal studies. However, a number of regulatory agencies have ignored all hazard findings. Reports of high levels of unconjugated (bioactive) serum BPA in dozens of human biomonitoring studies have also been rejected based on the prediction that the findings are due to assay contamination and that virtually all ingested BPA is rapidly converted to inactive metabolites. NIH and industry-sponsored round robin studies have demonstrated that serum BPA can be accurately assayed without contamination, while the FDA lab has acknowledged uncontrolled assay contamination. In reviewing the published BPA biomonitoring data, we find that assay contamination is, in fact, well controlled in most labs, and cannot be used as the basis for discounting evidence that significant and virtually continuous exposure to BPA must be occurring from multiple sources. PMID:25304273

Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabalka, G. W.

2005-06-28

The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

An engaged research study to assess the effect of a ‘real-world’ dietary intervention on urinary bisphenol A (BPA) levels in teenagers

PubMed Central

Galloway, Tamara S; Baglin, Nigel; Lee, Benjamin P; Kocur, Anna L; Shepherd, Maggie H; Steele, Anna M; Harries, Lorna W

2018-01-01

Objective Bisphenol A (BPA) has been associated with adverse human health outcomes and exposure to this compound is near-ubiquitous in the Western world. We aimed to examine whether self-moderation of BPA exposure is possible by altering diet in a real-world setting. Design An Engaged Research dietary intervention study designed, implemented and analysed by healthy teenagers from six schools and undertaken in their own homes. Participants A total of 94 students aged between 17 and 19 years from schools in the South West of the UK provided diet diaries and urine samples for analysis. Intervention Researcher participants designed a set of literature-informed guidelines for the reduction of dietary BPA to be followed for 7 days. Main outcome measures Creatinine-adjusted urinary BPA levels were taken before and after the intervention. Information on packaging and food/drink ingested was used to calculate a BPA risk score for anticipated exposure. A qualitative analysis was carried out to identify themes addressing long-term sustainability of the diet. Results BPA was detected in urine of 86% of participants at baseline at a median value of 1.22 ng/mL (IQR 1.99). No effect of the intervention diet on BPA levels was identified overall (P=0.25), but there was a positive association in those participants who showed a drop in urinary BPA concentration postintervention and their initial BPA level (P=0.003). Qualitative analysis identified themes around feelings of lifestyle restriction and the inadequacy of current labelling practices. Conclusions We found no evidence in this self-administered intervention study that it was possible to moderate BPA exposure by diet in a real-world setting. Furthermore, our study participants indicated that they would be unlikely to sustain such a diet long term, due to the difficulty in identifying BPA-free foods. PMID:29431133

A highly sensitive and specific capacitive aptasensor for rapid and label-free trace analysis of Bisphenol A (BPA) in canned foods.

PubMed

Mirzajani, Hadi; Cheng, Cheng; Wu, Jayne; Chen, Jiangang; Eda, Shigotoshi; Najafi Aghdam, Esmaeil; Badri Ghavifekr, Habib

2017-03-15

A rapid, highly sensitive, specific and low-cost capacitive affinity biosensor is presented here for label-free and single step detection of Bisphenol A (BPA). The sensor design allows rapid prototyping at low-cost using printed circuit board material by benchtop equipment. High sensitivity detection is achieved through the use of a BPA-specific aptamer as probe molecule and large electrodes to enhance AC-electroelectrothermal effect for long-range transport of BPA molecules toward electrode surface. Capacitive sensing technique is used to determine the bounded BPA level by measuring the sample/electrode interfacial capacitance of the sensor. The developed biosensor can detect BPA level in 20s and exhibits a large linear range from 1 fM to 10 pM, with a limit of detection (LOD) of 152.93 aM. This biosensor was applied to test BPA in canned food samples and could successfully recover the levels of spiked BPA. This sensor technology is demonstrated to be highly promising and reliable for rapid, sensitive and on-site monitoring of BPA in food samples. Copyright © 2016 Elsevier B.V. All rights reserved.

An engaged research study to assess the effect of a 'real-world' dietary intervention on urinary bisphenol A (BPA) levels in teenagers.

PubMed

Galloway, Tamara S; Baglin, Nigel; Lee, Benjamin P; Kocur, Anna L; Shepherd, Maggie H; Steele, Anna M; Harries, Lorna W

2018-02-03

Bisphenol A (BPA) has been associated with adverse human health outcomes and exposure to this compound is near-ubiquitous in the Western world. We aimed to examine whether self-moderation of BPA exposure is possible by altering diet in a real-world setting. An Engaged Research dietary intervention study designed, implemented and analysed by healthy teenagers from six schools and undertaken in their own homes. A total of 94 students aged between 17 and 19 years from schools in the South West of the UK provided diet diaries and urine samples for analysis. Researcher participants designed a set of literature-informed guidelines for the reduction of dietary BPA to be followed for 7 days. Creatinine-adjusted urinary BPA levels were taken before and after the intervention. Information on packaging and food/drink ingested was used to calculate a BPA risk score for anticipated exposure. A qualitative analysis was carried out to identify themes addressing long-term sustainability of the diet. BPA was detected in urine of 86% of participants at baseline at a median value of 1.22 ng/mL (IQR 1.99). No effect of the intervention diet on BPA levels was identified overall (P=0.25), but there was a positive association in those participants who showed a drop in urinary BPA concentration postintervention and their initial BPA level (P=0.003). Qualitative analysis identified themes around feelings of lifestyle restriction and the inadequacy of current labelling practices. We found no evidence in this self-administered intervention study that it was possible to moderate BPA exposure by diet in a real-world setting. Furthermore, our study participants indicated that they would be unlikely to sustain such a diet long term, due to the difficulty in identifying BPA-free foods. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bisphenol A (BPA) binding on full-length architectures of estrogen receptor.

PubMed

Liu, Yaquan; Qu, Kaili; Hai, Ying; Zhao, Chunyan

2018-08-01

Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full-length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen-like toxicity of BPA. In the present work, the consequence of BPA on full-length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi-domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full-length ER structure was dependent on long-range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue-residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full-size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen-like toxicity upon BPA binding with full-length ER. © 2018 Wiley Periodicals, Inc.

A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA).

PubMed

MacKay, Harry; Abizaid, Alfonso

2018-05-01

Bisphenol-A (BPA) is a well-known endocrine disrupting compound (EDC), capable of affecting the normal function and development of the reproductive system, brain, adipose tissue, and more. In spite of these diverse and well characterized effects, there is often comparatively little known about the molecular mechanisms which bring them about. BPA has traditionally been regarded as a primarily estrogenic EDC, and this perspective is often what guides research into the effects of BPA. However, emerging data from in-vitro and in-silico models show that BPA binds with a significant number of hormone receptors, including a number of nuclear and membrane-bound estrogen receptors, androgen receptors, as well as the thyroid hormone receptor, glucocorticoid receptor, and PPARγ. With this increased diversity of receptor targets, it may be possible to explain some of the more puzzling aspects of BPA pharmacology, including its non-monotonic dose-response curve, as well as experimental results which disagree with estrogenic positive controls. This paper reviews the receptors for which BPA has a known interaction, and discusses the implications of taking these receptors into account when studying the disruptive effects of BPA on growth and development. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

PubMed

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (p<0.05); and neonates' heart rate decreased 72.7% (p<0.05). In the chronic toxicity test, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Landowner’s Guide for Compatible Use of BPA Rights-of-Way

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Keeping transmission lines safe and reliable is a critical priority for the Bonneville Power Administration. The key element in achieving those objectives is BPA’s ability to construct, operate and maintain its transmission lines and rights-of-way — the area under and around the lines. You can help BPA keep these rights-of-way clear of trees, brush and structures that could affect the safety or reliability of the transmission system. Prior to planting, digging, or constructing within BPA’s rights-of-way, fill out BPA’s Land Use Application Form. The information you provide on the application helps BPA understand your proposed use and the potential impactsmore » to public safety, and the safety of our crews. BPA also reviews the application to determine whether a proposed use of land is compatible with the construction, operation and maintenance of BPA transmission lines. Coordinating with BPA early in your planning process can keep you safe and avoid wasting time and money.« less

PAEs and BPA removal in landfill leachate with Fenton process and its relationship with leachate DOM composition.

PubMed

He, Pin-Jing; Zheng, Zhong; Zhang, Hua; Shao, Li-Ming; Tang, Qiong-Yao

2009-08-15

An increasing attention has been paid to the trace endocrine disrupting compounds (EDCs) in landfill leachate. In this paper, the removal of EDCs including phthalic acid esters (PAEs) and bisphenol A (BPA) from the fresh and mature landfill leachate by Fenton treatment was studied. More than 40% of PAEs and about 62% of BPA were removed from the raw mature leachate while only 20% of PAEs and 37% of BPA in the raw fresh leachate were reduced, respectively. After the fresh and mature leachates were spiked with PAEs to 1.5 mg L(-1) and BPA to 0.08 mg L(-1), the removal efficiencies of BPA and PAEs increased to more than 88%. The results indicated that the removing efficiencies of the EDCs in the leachate had a relationship with their concentrations, and that the trace levels of EDCs in leachate challenged the treatment capacity of the Fenton process. Most of the EDCs in the enriched leachate were removed by oxidation, which had no clear correlation with the hydrophobicity of the EDCs. The flocculation played an important role in the removal of di-(2-ethylhexyl) phthalate that could not be completely oxidized in the Fenton process, in that the EDCs with high n-octanol/water partition coefficient inclined to precipitate after the Fenton process. The dissolved organic matter (DOM) in the fresh leachate inhibited the EDCs removal more than the DOM in the mature leachate did. Both the composition of the leachate DOM and the characteristics of the EDCs determined the removing efficiencies of the EDCs in the Fenton process.

Assessing bisphenol A (BPA) exposure risk from long-term dietary intakes in Taiwan.

PubMed

Chen, Wei-Yu; Shen, Yi-Pei; Chen, Szu-Chieh

2016-02-01

Dietary intake is the major bisphenol A (BPA) exposure route in humans, and is a cause of BPA-related adverse effects. The large-scale exposure risk of humans to BPA through dietary sources in Taiwan is less well studied. The aim of this study was to assess the average daily dose (ADD) and hazardous quotient (HQ) of BPA exposure risk from long-term dietary intake of BPA, as well as BPA concentrations in different age-sex groups in Taiwan. We reanalyzed the BPA concentrations of regular daily food sources (rice, poultry, livestock, seafood, protein, fruits, and vegetables) and used a national dietary survey to estimate the contribution of variance to ADDs and potential human health effect for different age-sex groups. This study found that the daily consumption of chicken, pork/beef, and seafood were estimated to be 33.77 (Male)/22.65 (Female), 91.70 (M)/66.35 (F), and 54.15 (M)/40.78 (F) g/day, respectively. The highest BPA ADD was found in the 6-9 years age group (95% CI=0.0006-0.0027 mg/kg-bw/day), whereas the lowest BPA ADD was in the ≥65 years age group (0.0002-0.0020 mg/kg-bw/day). Based on the latest EFSA guidelines (0.004 mg/kg-bw/day), the 97.5 percentile HQ of BPA intake in different age-sex groups in Taiwan posed no risks through dietary intake. However, a combination of multiple exposure routes and long-term exposure in specific populations may be of concern in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis.

PubMed

Strakovsky, Rita S; Wang, Huan; Engeseth, Nicki J; Flaws, Jodi A; Helferich, William G; Pan, Yuan-Xiang; Lezmi, Stéphane

2015-04-15

Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague-Dawley rats were dosed with vehicle (oil) or BPA (100μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. Copyright © 2015 Elsevier Inc. All rights reserved.

From BPA to its analogues: Is it a safe journey?

PubMed

Usman, Afia; Ahmad, Masood

2016-09-01

Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? Copyright © 2016. Published by Elsevier Ltd.

Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol A (BPA) and Its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish.

PubMed

Moreman, John; Takesono, Aya; Trznadel, Maciej; Winter, Matthew J; Perry, Alexis; Wood, Mark E; Rogers, Nicola J; Kudoh, Tetsuhiro; Tyler, Charles R

2018-06-05

Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack of agreement on its mechanism(s) of action likely stem from comparisons between in vivo and in vitro test systems and potential multiple effects pathways. In rodents, in vivo, metabolic activation of BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported to be up to 1000 times more potent as an estrogen than BPA. We investigated the estrogenic effects and estrogen receptor signaling pathway(s) of BPA and MBP following early life exposure using a transgenic, estrogen responsive (ERE-TG) zebrafish and a targeted morpholino approach to knockdown the three fish estrogen receptor (ER) subtypes. The functional consequences of BPA exposure on the cardiovascular system of zebrafish larvae were also examined. The heart atrioventricular valves and the bulbus arteriosus were primary target tissues for both BPA and MBP in the ERE-TG zebrafish, and MBP was approximately 1000-fold more potent than BPA as an estrogen in these tissues. Estrogen receptor knockdown with morpholinos indicated that the estrogenic responses in the heart for both BPA and MBP were mediated via an estrogen receptor 1 (esr1) dependent pathway. At the highest BPA concentration tested (2500 μg/L), alterations in the atrial:ventricular beat ratio indicated a functional impact on the heart of 5 days post fertilization (dpf) larvae, and there was also a significantly reduced heart rate in these larvae at 14 dpf. Our findings indicate that some of the reported adverse effects on heart function associated with BPA exposure (in mammals) may act through an estrogenic mechanism, but that fish are unlikely to be susceptible to adverse effects on heart development for environmentally relevant exposures.

Endocrine activity of alternatives to BPA found in thermal paper in Switzerland.

PubMed

Goldinger, Daniela M; Demierre, Anne-Laure; Zoller, Otmar; Rupp, Heinz; Reinhard, Hans; Magnin, Roxane; Becker, Thomas W; Bourqui-Pittet, Martine

2015-04-01

Alternatives to bisphenol A (BPA) are more and more used in thermal paper receipts. To get an overview of the situation in Switzerland, 124 thermal paper receipts were collected and analyzed. Whereas BPA was detected in most samples (n=100), some alternatives, namely bisphenol S (BPS), Pergafast® 201 and D-8 have been found in 4, 11 and 9 samples respectively. As no or few data on their endocrine activity are available, these chemicals and bisphenol F (BPF) were tested in vitro using the H295R steroidogenesis assay. 17β-Estradiol production was induced by BPA and BPF, whereas free testosterone production was inhibited by BPA and BPS. Both non-bisphenol substances did not show significant effects. The binding affinity to 16 proteins and the toxicological potential (TP) were further calculated in silico using VirtualToxLab™. TP values lay between 0.269 and 0.476 and the main target was the estrogen receptor β (84.4 nM to 1.33 μM). A substitution of BPA by BPF and BPS should be thus considered with caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and Pergafast® 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring.

PubMed

Correia-Sá, Luísa; Kasper-Sonnenberg, Monika; Schütze, André; Pälmke, Claudia; Norberto, Sónia; Calhau, Conceição; Domingues, Valentina F; Koch, Holger M

2017-12-01

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake

Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

PubMed

Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

2016-06-07

Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.

Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.

Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C,more » and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male

BPA Facts Pocket Edition

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

BPA will be an engine of the Northwest’s economic prosperity and environmental sustainability. BPA’s actions advance a Northwest power system that is a national leader in providing: • high reliability; • low rates consistent with sound business principles; • responsible environmental stewardship; and • accountability to the region. We deliver on these public responsibilities through a commercially successful business.

Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after balloon pulmonary angioplasty (BPA): Preliminary results.

PubMed

Koike, Hirofumi; Sueyoshi, Eijun; Sakamoto, Ichiro; Uetani, Masataka; Nakata, Tomoo; Maemura, Kouji

2016-09-01

Balloon pulmonary angioplasty (BPA) is a treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Its effect on pulmonary perfusion has not been quantified; we examined the clinical significance of pulmonary blood volume (PBV) using dual-energy computed tomography (DECT) in patients with CTEPH undergoing BPA. In this retrospective study of 16 BPAs in eight female patients with CTEPH, we evaluated both-lung (n=16), right- or left-lung (n=32), and three right- or left-segment (upper, middle, and lower) (n=96) PBVs before and after BPA, using DECT. We evaluated the relationships between improvement in lung PBV and pulmonary artery (PA) pressure (PAP), cardiac index (CI), pulmonary vascular resistance (PVR), and 6-min walking distance. We measured PA enhancement (PAenh) on DECT images and calculated lung PBV/PAenh to adjust timing. Pre- and post-BPA 6-segment lung PBV/PAenh were 0.067±0.021 and 0.077±0.019, respectively, in the treated segment (p<0.0001). There were significant positive correlations between pre- to post-BPA improvements in both-lung PBV/PAenh and PAP (R=0.69, p=0.005), PVR (R=0.56, p=0.03), and 6-min walking distance (R=0.67, p=0.01). Improved PBV after BPA, reflecting increased lung perfusion, was positively correlated with PAP, PVR, and 6-min walking distance. Lung PBV may be an indicator of BPA treatment effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum.

PubMed

Szymanska, Kamila; Makowska, Krystyna; Gonkowski, Slawomir

2018-03-20

Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT-used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms.

[Substance monograph on bisphenol A (BPA) - reference and human biomonitoring (HBM) values for BPA in urine. Opinion of the Human Biomonitoring Commission of the German Federal Environment Agency (UBA)].

PubMed

2012-09-01

Bisphenol A (BPA) is used for the production of polycarbonates and synthetic resins. Many of the items that contain BPA, for example polycarbonate bottles and coated cans, are commodities from which BPA can migrate into food and drinks, resulting in ubiquitous exposure of the population. Numerous animal studies and in vitro tests have shown that BPA acts as an "endocrine disruptor". Because of the still incomplete understanding of the complex and contradictory effects of BPA at doses below the NOAEL, the toxicological significance of recent findings is uncertain. The German HBM Commission takes notice that the risk assessment is currently in flux and that in the EU and other countries precautionary bans on BPA have been introduced. In the light of the extensive and growing body of literature, the Commission does not see itself in a position to resolve this controversy, nor to answer the question of the relevance of observed effects of low BPA doses on human health. The Commission has derived reference values (RV95) and TDI-based HBM I values for total BPA in urine. The RV95 values are 30 μg/l for 3-5 year olds, 15 μg/l for 6-14 year olds, and 7 μg/l for 20-29 year olds. The HBM I value for children is 1.5 mg/l and 2.5 mg/l for adults, respectively. The Commission emphasizes that the HBM values will require immediate adjustment should the current TDI of 0.05 mg/kg bw/day be changed. For the practical application of HBM, the Commission recommends an assessment based on the RV95. Confirmed exceedance of the RV95 by repeat measurements should prompt a search for the possible source(s), following the ALARA principle.

In vivo maternal and in vitro BPA exposure effects on hypothalamic neurogenesis and appetite regulators.

PubMed

Desai, Mina; Ferrini, Monica G; Han, Guang; Jellyman, Juanita K; Ross, Michael G

2018-07-01

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured. For in vitro BPA exposure, primary hypothalamic NPCs from healthy newborns were utilized. In both cases, we studied the effects of BPA on NPC proliferation and differentiation, including putative signal and appetite factors. Maternal BPA increased hypothalamic NPC proliferation and differentiation in newborns, in conjunction with increased neuroproliferative (Hes1) and proneurogenic (Ngn3) protein expression. With NPC differentiation, BPA exposure increased appetite peptide and reduced satiety peptide expression. In vitro BPA-treated control NPCs showed results that were consistent with in vivo data (increase appetite vs satiety peptide expression) and further showed a shift towards neuronal versus glial fate as well as an increase in the epigenetic regulator lysine-specific histone demethylase1 (LSD1). These findings emphasize the vulnerability of stem-cell populations that are involved in life-long regulation of metabolic homeostasis to epigenetically-mediated endocrine disruption by BPA during early life. Copyright © 2018. Published by Elsevier Inc.

Determination of Highly Sensitive Biological Cell Model Systems to Screen BPA-Related Health Hazards Using Pathway Studio.

PubMed

Ryu, Do-Yeal; Rahman, Md Saidur; Pang, Myung-Geol

2017-09-06

Bisphenol-A (BPA) is a ubiquitous endocrine-disrupting chemical. Recently, many issues have arisen surrounding the disease pathogenesis of BPA. Therefore, several studies have been conducted to investigate the proteomic biomarkers of BPA that are associated with disease processes. However, studies on identifying highly sensitive biological cell model systems in determining BPA health risk are lacking. Here, we determined suitable cell model systems and potential biomarkers for predicting BPA-mediated disease using the bioinformatics tool Pathway Studio. We compiled known BPA-mediated diseases in humans, which were categorized into five major types. Subsequently, we investigated the differentially expressed proteins following BPA exposure in several cell types, and analyzed the efficacy of altered proteins to investigate their associations with BPA-mediated diseases. Our results demonstrated that colon cancer cells (SW480), mammary gland, and Sertoli cells were highly sensitive biological model systems, because of the efficacy of predicting the majority of BPA-mediated diseases. We selected glucose-6-phosphate dehydrogenase (G6PD), cytochrome b-c1 complex subunit 1 (UQCRC1), and voltage-dependent anion-selective channel protein 2 (VDAC2) as highly sensitive biomarkers to predict BPA-mediated diseases. Furthermore, we summarized proteomic studies in spermatozoa following BPA exposure, which have recently been considered as another suitable cell type for predicting BPA-mediated diseases.

Load Composition Model Workflow (BPA TIP-371 Deliverable 1A)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chassin, David P.; Cezar, Gustavo V.

This project is funded under Bonneville Power Administration (BPA) Strategic Partnership Project (SPP) 17-005 between BPA and SLAC National Accelerator Laboratory. The project in a BPA Technology Improvement Project (TIP) that builds on and validates the Composite Load Model developed by the Western Electric Coordinating Council's (WECC) Load Modeling Task Force (LMTF). The composite load model is used by the WECC Modeling and Validation Work Group to study the stability and security of the western electricity interconnection. The work includes development of load composition data sets, collection of load disturbance data, and model development and validation. This work supports reliablemore » and economic operation of the power system. This report was produced for Deliverable 1A of the BPA TIP-371 Project entitled \\TIP 371: Advancing the Load Composition Model". The deliverable documents the proposed work ow for the Composite Load Model, which provides the basis for the instrumentation, data acquisition, analysis and data dissemination activities addressed by later phases of the project.« less

Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled.

PubMed

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-09-13

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized industrial chemicals worldwide, with the ability to interfere with/or mimic estrogenic hormones with associated biological responses. Environmental human exposure to this endocrine disruptor, mostly through oral intake, is considered a generalized phenomenon, particularly in developed countries. However, in the context of occupational exposure, non-dietary exposure sources (e.g., air and contact) cannot be underestimated. Here, we performed a review of the literature on BPA occupational exposure and associated health effects. Relevantly, the authors only identified 19 studies from 2009 to 2017 that demonstrate that occupationally exposed individuals have significantly higher detected BPA levels than environmentally exposed populations and that the detection rate of serum BPA increases in relation to the time of exposure. However, only 12 studies performed in China have correlated potential health effects with detected BPA levels, and shown that BPA-exposed male workers are at greater risk of male sexual dysfunction across all domains of sexual function; also, endocrine disruption, alterations to epigenetic marks (DNA methylation) and epidemiological evidence have shown significant effects on the offspring of parents exposed to BPA during pregnancy. This overview raises awareness of the dramatic and consistent increase in the production and exposure of BPA and creates urgency to assess the actual exposure of workers to this xenoestrogen and to evaluate potential associated adverse health effects.

Determination of Highly Sensitive Biological Cell Model Systems to Screen BPA-Related Health Hazards Using Pathway Studio

PubMed Central

Ryu, Do-Yeal

2017-01-01

Bisphenol-A (BPA) is a ubiquitous endocrine-disrupting chemical. Recently, many issues have arisen surrounding the disease pathogenesis of BPA. Therefore, several studies have been conducted to investigate the proteomic biomarkers of BPA that are associated with disease processes. However, studies on identifying highly sensitive biological cell model systems in determining BPA health risk are lacking. Here, we determined suitable cell model systems and potential biomarkers for predicting BPA-mediated disease using the bioinformatics tool Pathway Studio. We compiled known BPA-mediated diseases in humans, which were categorized into five major types. Subsequently, we investigated the differentially expressed proteins following BPA exposure in several cell types, and analyzed the efficacy of altered proteins to investigate their associations with BPA-mediated diseases. Our results demonstrated that colon cancer cells (SW480), mammary gland, and Sertoli cells were highly sensitive biological model systems, because of the efficacy of predicting the majority of BPA-mediated diseases. We selected glucose-6-phosphate dehydrogenase (G6PD), cytochrome b-c1 complex subunit 1 (UQCRC1), and voltage-dependent anion-selective channel protein 2 (VDAC2) as highly sensitive biomarkers to predict BPA-mediated diseases. Furthermore, we summarized proteomic studies in spermatozoa following BPA exposure, which have recently been considered as another suitable cell type for predicting BPA-mediated diseases. PMID:28878155

The Effects of Bisphenol A (BPA) on ErbB2 Positive Breast Cancer

DTIC Science & Technology

2010-11-01

development and progression. We have previously shown that either prenatal ( gestational days 10-21) only exposure to BPA or prepubertal (postpartum days...receptor (PR) in the mammary gland, and increased lateral branching (30). With gestational exposure alone, BPA has been reported to increase the...ductal hyperplasia and carcinoma in situ (32). Gestational exposure to BPA has been reported to result in reproductive and endocrine disruption in

BPA-Induced Deregulation Of Epigenetic Patterns: Effects On Female Zebrafish Reproduction.

PubMed

Santangeli, Stefania; Maradonna, Francesca; Gioacchini, Giorgia; Cobellis, Gilda; Piccinetti, Chiara Carla; Dalla Valle, Luisa; Carnevali, Oliana

2016-02-25

Bisphenol A (BPA) is one of the commonest Endocrine Disruptor Compounds worldwide. It interferes with vertebrate reproduction, possibly by inducing deregulation of epigenetic mechanisms. To determine its effects on female reproductive physiology and investigate whether changes in the expression levels of genes related to reproduction are caused by histone modifications, BPA concentrations consistent with environmental exposure were administered to zebrafish for three weeks. Effects on oocyte growth and maturation, autophagy and apoptosis processes, histone modifications, and DNA methylation were assessed by Real-Time PCR (qPCR), histology, and chromatin immunoprecipitation combined with qPCR analysis (ChIP-qPCR). The results showed that 5 μg/L BPA down-regulated oocyte maturation-promoting signals, likely through changes in the chromatin structure mediated by histone modifications, and promoted apoptosis in mature follicles. These data indicate that the negative effects of BPA on the female reproductive system may be due to its upstream ability to deregulate epigenetic mechanism.

Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be Unveiled

PubMed Central

2017-01-01

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized industrial chemicals worldwide, with the ability to interfere with/or mimic estrogenic hormones with associated biological responses. Environmental human exposure to this endocrine disruptor, mostly through oral intake, is considered a generalized phenomenon, particularly in developed countries. However, in the context of occupational exposure, non-dietary exposure sources (e.g., air and contact) cannot be underestimated. Here, we performed a review of the literature on BPA occupational exposure and associated health effects. Relevantly, the authors only identified 19 studies from 2009 to 2017 that demonstrate that occupationally exposed individuals have significantly higher detected BPA levels than environmentally exposed populations and that the detection rate of serum BPA increases in relation to the time of exposure. However, only 12 studies performed in China have correlated potential health effects with detected BPA levels, and shown that BPA-exposed male workers are at greater risk of male sexual dysfunction across all domains of sexual function; also, endocrine disruption, alterations to epigenetic marks (DNA methylation) and epidemiological evidence have shown significant effects on the offspring of parents exposed to BPA during pregnancy. This overview raises awareness of the dramatic and consistent increase in the production and exposure of BPA and creates urgency to assess the actual exposure of workers to this xenoestrogen and to evaluate potential associated adverse health effects. PMID:29051454

BPA and NP removal from municipal wastewater by tropical horizontal subsurface constructed wetlands.

PubMed

Toro-Vélez, A F; Madera-Parra, C A; Peña-Varón, M R; Lee, W Y; Bezares-Cruz, J C; Walker, W S; Cárdenas-Henao, H; Quesada-Calderón, S; García-Hernández, H; Lens, P N L

2016-01-15

It has been recognized that numerous synthetic compounds like Bisphenol A (BPA) and nonylphenols (NP) are present in effluents from wastewater treatment plants (WWTP) at levels of parts per billion (μg L(-1)) or even parts per trillion (ng L(-1)) with a high potential to cause endocrine disruption in the aquatic environment. Constructed wetlands (CW) are a cost-effective wastewater treatment alternative with promising performance to treat these afore mentioned compounds. This research was aimed to evaluate the efficacy of CW treatment of WWTP effluent for mitigating the effects endocrine disrupting compounds (EDCs). This research goal was accomplished by (1) quantifying the removal of BPA and NP in CWs; (2) isolating CW fungal strains and testing for laccase production; and (3) performing endocrine disruption (reproduction) bioassays using the fruit fly Drosophila melanogaster. Three pilot scale horizontal subsurface flow constructed wetlands (HSSF-CW) were operated for eight weeks: one planted with Phragmites australis; one planted with Heliconia psitacorum; and one unplanted. The Heliconia CW showed a removal efficiency of 73.3(± 19%) and 62.8(± 20.1%) for BPA and NP, respectively; while the Phragmites CW demonstrated a similar removal for BPA (70.2 ± 27%) and lower removal efficiency for NP 52.1(± 37.1%).The unplanted CW achieved 62.2 (± 33%) removal for BPA and 25.3(± 37%) removal for NP. Four of the eleven fungal strains isolated from the Heliconia-CW showed the capacity to produce laccase. Even though complete removal of EDCs was not achieved by the CWs, the bioassay confirmed a significant improvement (p < 0.05) in fly viability for all CWs, with Heliconia sp. being the most effective at mitigating adverse effects on first and second generational reproduction. This study showed that a CW planted with a native Heliconia sp. CW demonstrated a higher removal of endocrine disrupting compounds and better mitigation of reproductive disruption in the

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

PubMed Central

Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

2012-01-01

Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome.

PubMed

Bolten, Marcel; Delley, Cyrille L; Leibundgut, Marc; Boehringer, Daniel; Ban, Nenad; Weber-Ban, Eilika

2016-12-06

Mycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. Recently, a non-ATPase activator termed Bpa (bacterial proteasome activator) was shown to support an alternate proteasomal degradation pathway. Here, we present the cryo-electron microscopy (cryo-EM) structure of Bpa in complex with the 20S core particle (CP). For docking into the cryo-EM density, we solved the X-ray structure of Bpa, showing that it forms tight four-helix bundles arranged into a 12-membered ring with a 40 Å wide central pore and the C-terminal helix of each protomer protruding from the ring. The Bpa model was fitted into the cryo-EM map of the Bpa-CP complex, revealing its architecture and striking symmetry mismatch. The Bpa-CP interface was resolved to 3.5 Å, showing the interactions between the C-terminal GQYL motif of Bpa and the proteasome α-rings. This docking mode is related to the one observed for eukaryotic activators with features specific to the bacterial complex. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function

PubMed Central

Chen, Yichang; Qiu, Zhiqun; Lee, Dong Yeon; Telesca, Donatello; Yang, Xia; Allard, Patrick

2016-01-01

Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures. PMID:27472198

DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

PubMed

Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

2016-03-01

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

Removal of bisphenol A (BPA) from water by various nanofiltration (NF) and reverse osmosis (RO) membranes.

PubMed

Yüksel, Suna; Kabay, Nalan; Yüksel, Mithat

2013-12-15

The removal of an endocrine disrupting compound, bisphenol A (BPA), from model solutions by selected nanofiltration (NF) and reverse osmosis (RO) membranes was studied. The commercially available membranes NF 90, NF 270, XLE BWRO, BW 30 (Dow FilmTech), CE BWRO and AD SWRO (GE Osmonics) were used to compare their performances for BPA removal. The water permeability coefficients, rejection of BPA and permeate flux values were calculated for all membranes used. No significant changes in their BPA removal were observed for all tight polyamide based NF and RO membranes tested except for loose NF 270 membrane. The polyamide based membranes exhibited much better performance than cellulose acetate membrane for BPA removal. Almost a complete rejection (≥ 98%) for BPA was obtained with three polyamide based RO membranes (BW 30, XLE BWRO and AD SWRO). But cellulose acetate based CE BWRO membrane offered a low and variable (10-40%) rejection for BPA. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro percutaneous absorption and metabolism of Bisphenol A (BPA) through fresh human skin.

PubMed

Toner, Frank; Allan, Graham; Dimond, Stephen S; Waechter, John M; Beyer, Dieter

2018-03-01

Bisphenol A (BPA) is a high production volume compound. It is mainly used as a monomer to make polymers for various applications including food-contact materials. The primary route of exposure to BPA in the general population is through oral intake (EFSA 2015) however, other potential sources of exposure have also been identified, such as dermal contact. In the present study, the percutaneous absorption through human skin has been investigated in an in vitro study according to OECD TG 428 (Skin Absorption: In Vitro Method). In order to investigate potential dermal BPA metabolism during absorption, radiolabelled BPA was applied to fresh, metabolically competent, human skin samples (ring labelled 14 C BPA concentrations tested were 2.4, 12, 60 and 300mg/L). Measured as total radioactivity the mean absorbed dose (receptor compartment) ranged from 1.7-3.6% of the applied doses and the dermal delivery (epidermis+dermis+receptor compartment), sometimes also named bioavailable dose was 16-20% of the applied doses, with the majority of the radioactivity associated with epidermis compared to dermis and receptor fluid. No metabolism was observed in any of the epidermis samples; however some metabolism was observed in dermis and receptor fluid samples with formation of BPA-glucuronide and BPA-sulfate, and some polar metabolites. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.

PubMed

Hindman, Andrea R; Mo, Xiaokui Molly; Helber, Hannah L; Kovalchin, Claire E; Ravichandran, Nanditha; Murphy, Alina R; Fagan, Abigail M; St John, Pamela M; Burd, Craig J

2017-10-01

In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes. Copyright © 2017 Endocrine Society.

Effect of Bisphenol A on the extremophilic microalgal strain Picocystis sp. (Chlorophyta) and its high BPA removal ability.

PubMed

Ben Ouada, Sabrine; Ben Ali, Rihab; Leboulanger, Christophe; Ben Ouada, Hatem; Sayadi, Sami

2018-08-30

Bisphenol A (BPA) effects and removal by an alkaliphilic chlorophyta, Picocystis, were assessed. BPA at low concentrations (0-25 mg L -1 ) did not inhibit the Picocystis growth and photosynthesis during 5 days of exposure. At higher BPA concentrations (50 and 75 mg L -1 ), the growth inhibition did not exceed 43%. The net photosynthetic activity was dramatically reduced at high BPA concentrations while, the PSII activity was less affected. The exposure to increasing BPA concentrations induced an oxidative stress in Picocystis cells, as evidenced by increased malondialdehyde content and the over-expression of antioxidant activities (ascorbate peroxydase, gluthation-S-transferase and catalase). Picocystis exhibited high BPA removal efficiency, reaching 72% and 40% at 25 and 75 mg L -1 BPA. BPA removal was ensured mainly by biodegradation/biotransformation processes. Based on these results, the extended tolerance and the high removal ability of Picocystis make her a promising specie for use in BPA bioremediation. Copyright © 2018. Published by Elsevier Inc.

Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas

PubMed Central

2013-01-01

Background Boron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of 10B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice. Materials and methods Tumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation. Results The 10B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT. Conclusions These results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels. PMID:24295213

Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep.

PubMed

Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Lumeng, Carey; Ye, Wen; Pease, Anthony; Padmanabhan, Vasantha

2016-02-01

Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutaneous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy. Copyright © 2016 the American Physiological Society.

Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep

PubMed Central

Veiga-Lopez, Almudena; Moeller, Jacob; Sreedharan, Rohit; Singer, Kanakadurga; Ye, Wen; Pease, Anthony

2015-01-01

Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutanous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy. PMID:26646100

The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

PubMed

Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

2016-01-01

Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects.

Contribution of a submerged membrane bioreactor in the treatment of synthetic effluent contaminated by Bisphenol-A: mechanism of BPA removal and membrane fouling.

PubMed

Seyhi, Brahima; Drogui, Patrick; Buelna, Gerardo; Azaïs, Antonin; Heran, Marc

2013-09-01

A submerged membrane bioreactor has been operated at the laboratory scale for the treatment of a synthetic effluent containing Bisphenol-A (BPA). COD, NH4-N, PO4-P and BPA were eliminated respectively, at 99%, 99%, 61% and 99%. The increase of volumetric loading rate from 0 to 21.6 g/m(3)/d did not affect the performance of the MBR system. However, the removal rate decreased rapidly when the BPA loading rate increased above 21.6 g/m(3)/d. The adsorption process of BPA on the biomass was very well described by Freundlich and Langmuir isotherms. Subsequently, biodegradation of BPA occurred and followed the first order kinetic reaction, with a constant rate of 1.13 ± 0.22 h(-1). During treatment, membrane fouling was reversible in the first 84 h of filtration, and then became irreversible. The membrane fouling was mainly due to the accumulation of suspended solid and development of biofilm on the membrane surface. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enhanced heterogeneous photo-Fenton process modified by magnetite and EDDS: BPA degradation.

PubMed

Huang, Wenyu; Luo, Mengqi; Wei, Chaoshuai; Wang, Yinghui; Hanna, Khalil; Mailhot, Gilles

2017-04-01

In this research, magnetite and ethylenediamine-N,N'-disuccinic acid (EDDS) are used in a heterogeneous photo-Fenton system in order to find a new way to remove organic contaminants from water. Influence of different parameters including magnetite dosage, EDDS concentration, H 2 O 2 concentration, and pH value were evaluated. The effect of different radical species including HO · and HO 2 · /O 2 ·- was investigated by addition of different scavengers into the system. The addition of EDDS improved the heterogeneous photo-Fenton degradation of bisphenol A (BPA) through the formation of photochemically efficient Fe-EDDS complex. This effect is dependent on the H 2 O 2 and EDDS concentrations and pH value. The high performance observed at pH 6.2 could be explained by the ability of O 2 ·- to generate Fe(II) from Fe(III) species reduction. GC-MS analysis suggested that the cleavage of the two benzene rings is the first degradation step followed by oxidation leading to the formation of the benzene derivatives. Then, the benzene ring was opened due to the attack of HO · radicals producing short-chain organic compounds of low molecular weight like glycerol and ethylene glycol. These findings regarding the capability of EDDS/magnetite system to promote heterogeneous photo-Fenton oxidation have important practical implications for water treatment technologies.

A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

PubMed

Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A; Perry, Amy; D'Addezio, Alyssa S; Cushing, Bruce S; Patisaul, Heather B

2014-10-01

Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS)

PubMed Central

Chandra, S.; Ahmad, T.; Barth, R. F.; Kabalka, G. W.

2014-01-01

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 (10B) atoms to individual tumor cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumor cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B atoms reflects both bound and free pools of boron in individual tumor cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular scale resolution by clinically applicable techniques such as PET and MRI. In this study, secondary ion mass spectrometry (SIMS) based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high grade gliomas, recurrent tumors of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumor cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS).

PubMed

Chandra, S; Ahmad, T; Barth, R F; Kabalka, G W

2014-06-01

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 ((10)B) atoms to individual tumour cells. Cell killing results from the (10)B (n, α)(7) Li neutron capture and fission reactions that occur if a sufficient number of (10)B atoms are localized in the tumour cells. Intranuclear (10)B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of (10)B atoms reflects both bound and free pools of boron in individual tumour cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular-scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high-grade gliomas, recurrent tumours of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This

Unusually high levels of bisphenol A (BPA) in thermal paper cash register receipts (CRs): development and application of a robust LC-UV method to quantify BPA in CRs.

PubMed

Babu, Sainath; Uppu, Sannihith N; Martin, Brittany; Agu, Ogad A; Uppu, Rao M

2015-01-01

We have developed a simple, reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of bisphenol A (BPA) in thermal paper cash register receipts (CRs). The method is suitable for analysis of other types of bisphenols and it involves an overnight extraction of CRs with acetonitrile (AN) at 50 °C followed by the HPLC analysis on a Supelcosil LC18 column (150 × 4.6 mm, particle size: 5 μ) using 50% AN in water as the mobile phase (5 min, isocratic). The composition of AN in the mobile phase changed to 100% over a 10 min period (linear gradient) and then held at 100% AN for 10 min (isocratic). The flow rate was set at 1 mL/min (injection volume: 20 μL) and the eluent was monitored at 234 nm. The authentic BPA eluted with a retention time of 5.9 min and gave a linear detector response in the concentration range of 0.23-50 mg/L. BPA in the CR extracts also eluted with the same retention and had identical absorbance properties as the standard. When CR extracts were co-injected with authentic BPA, they were resolved as a single peak. Further, GC/MS/EI analysis of authentic BPA and the HPLC-purified CR extracts have identical ion chromatograms and fragmentation of the molecular ion (m/z = 228). We have analyzed 170 CRs collected from 62 different vendors including supermarkets, fast food restaurants, gas stations and banking outlets. Almost all cash receipts (n = 168) showed the presence of BPA in the concentration range of 0.45-4.26% (M ± SD, 1.54 ± 0.73%).

Prostate Cancer Risk and DNA Methylation Signatures in Aging Rats following Developmental BPA Exposure: A Dose-Response Analysis.

PubMed

Prins, Gail S; Ye, Shu-Hua; Birch, Lynn; Zhang, Xiang; Cheong, Ana; Lin, Han; Calderon-Gierszal, Esther; Groen, Jacob; Hu, Wen-Yang; Ho, Shuk-Mei; van Breemen, Richard B

2017-07-11

Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes. Male neonatal Sprague-Dawley rats were briefly exposed to 0.1 to 5,000 μg BPA/kg BW on postnatal days (PND) 1, 3, and 5. Individual prostate lobes plus periurethral prostatic ducts were evaluated at 7 mo or 1 y of age without or with adult testosterone plus estradiol (T+E) to promote carcinogenesis. DNA methylation of five genes was quantified by bisulfite genomic sequencing in d-200 dorsal prostates across BPA doses. Serum free-BPA and BPA-glucuronide were quantitated in sera of individual PND 3 pups collected 1 hr postexposure utilizing ultra-high-pressure tandem mass spectrometry (UHPLC-MS-MS). The lowest BPA dose initiated maximal hormonal carcinogenesis in lateral prostates despite undetectable free BPA 1 hr postexposure. Further, prostatic intraepithelial neoplasia (PIN) progressed to carcinoma in rats given neonatal low-dose BPA with adult T+E but not in rats given adult T+E alone. The dorsal and ventral lobes and periurethral prostatic ducts exhibited a nonmonotonic dose response with peak PIN, proliferation and apoptotic values at 10–100 μg/kg BW. This was paralleled by nonmonotonic and dose-specific DNA hypomethylation of genes that confer carcinogenic risk, with greatest hypomethylation at the lowest BPA doses. Developmental BPA exposures heighten prostate cancer susceptibility in a complex dose- and lobe-specific manner. Importantly, elevated carcinogenic risk is found at doses that yield undetectable serum free BPA. Dose

Prostate Cancer Risk and DNA Methylation Signatures in Aging Rats following Developmental BPA Exposure: A Dose–Response Analysis

PubMed Central

Ye, Shu-Hua; Birch, Lynn; Zhang, Xiang; Cheong, Ana; Lin, Han; Calderon-Gierszal, Esther; Groen, Jacob; Hu, Wen-Yang; Ho, Shuk-Mei; van Breemen, Richard B.

2017-01-01

Background: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. Objectives: A complete BPA dose–response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes. Methods: Male neonatal Sprague-Dawley rats were briefly exposed to 0.1 to 5,000μg BPA/kg BW on postnatal days (PND) 1, 3, and 5. Individual prostate lobes plus periurethral prostatic ducts were evaluated at 7 mo or 1 y of age without or with adult testosterone plus estradiol (T+E) to promote carcinogenesis. DNA methylation of five genes was quantified by bisulfite genomic sequencing in d-200 dorsal prostates across BPA doses. Serum free-BPA and BPA-glucuronide were quantitated in sera of individual PND 3 pups collected 1 hr postexposure utilizing ultra-high-pressure tandem mass spectrometry (UHPLC-MS-MS). Results: The lowest BPA dose initiated maximal hormonal carcinogenesis in lateral prostates despite undetectable free BPA 1 hr postexposure. Further, prostatic intraepithelial neoplasia (PIN) progressed to carcinoma in rats given neonatal low-dose BPA with adult T+E but not in rats given adult T+E alone. The dorsal and ventral lobes and periurethral prostatic ducts exhibited a nonmonotonic dose response with peak PIN, proliferation and apoptotic values at 10–100μg/kg BW. This was paralleled by nonmonotonic and dose-specific DNA hypomethylation of genes that confer carcinogenic risk, with greatest hypomethylation at the lowest BPA doses. Conclusions: Developmental BPA exposures heighten prostate cancer susceptibility in a complex dose- and lobe-specific manner. Importantly, elevated carcinogenic risk is found at

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study

PubMed Central

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet

2017-01-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. PMID:28324068

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study.

PubMed

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet; Flaws, Jodi A

2017-06-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. Copyright © 2017 Endocrine Society.

Assessment of the Geothermal Potential Within the BPA Marketing Area.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lund, John W.; Allen, Eliot D.

1980-07-01

The potential of geothermal energy is estimated that can be used for direct heat applications and electrical power generation within the Bonneville Power Administration (BPA) marketing area. The BPA marketing area includes three principal states of Oregon, Washington, and Idaho and portions of California, Montana, Wyoming, Nevada, and Utah bordering on these three states. This area covers approximately 384,000 square miles and has an estimated population of 6,760,000. The total electrical geothermal potential within this marketing area is 4077 MW/sub e/ from hydrothermal resources and 16,000 MW/sub e/ from igneous systems, whereas the total thermal (wellhead) potential is 16.15 xmore » 10/sup 15/ Btu/y. Approximately 200 geothermal resource sites were initially identified within the BPA marketing area. This number was then reduced to about 100 sites thought to be the most promising for development by the year 2000. These 100 sites, due to load area overlap, were grouped into 53 composite sites; 21-3/4 within BPA preference customer areas and 31-1/4 within nonpreference customer areas. The geothermal resource potential was then estimated for high-temperature (> 302/sup 0/F = 150/sup 0/C), intermediate-temperature (194 to 302/sup 0/F = 90 to 150/sup 0/C), and low-temperature (< 194/sup 0/F = 90/sup 0/C) resources.« less

Review of BPA Funded Sturgeon, Resident Fish and Wildlife Projects for 1990/1991.

DOE Office of Scientific and Technical Information (OSTI.GOV)

United States. Bonneville Power Administration.

1990-12-01

The Bonneville Power Administration (BPA) held a public meeting on November 19--21, 1991, for the purpose of review, coordination, and consultation of the BPA-funded projects for sturgeon, resident fish, and wildlife in the Columbia River Basin (Basin). The comments received after the meeting were favorable and the participants agreed that the meeting was stimulating and productive. The information exchanged should lead to better coordination with other projects throughout the Basin. This document list the projects by title, the project leaders and BPA's project officers, and an abstract of each leader's presentation.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model.

PubMed

Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Thorp, Silvia; Monti Hughes, Andrea; Molinari, Ana J; Garabalino, Marcela A; Heber, Elisa M; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Trivillin, Verónica A; Schwint, Amanda E

2012-08-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT, boronophenylalanine (BPA) + neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA-BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks post-treatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA-BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mg fell significantly to 19 ± 16 mg for BPA-BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA-BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA-BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veiga-Lopez, A.; Beckett, E.M.; Abi Salloum, B.

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changesmore » and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. - Highlights: • Prenatal BPA shortens interval between estradiol rise and preovulatory LH surge. • Prenatal BPA affects follicular count trajectory and follicular wave occurrence. • Prenatal BPA does not affect ovulatory rate and progesterone dynamics.« less

Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure.

PubMed

Ogi, Hiroshi; Itoh, Kyoko; Ikegaya, Hiroshi; Fushiki, Shinji

2015-09-01

Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes. C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams. The IntelliCage behavioral experiments were conducted from P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions were measured by high performance liquid chromatography. Furthermore, the associations between the neurotransmitter levels and the behavioral indices were statistically analyzed. In females exposed to BPA, the GABA and Glu levels in almost all regions, and the NE levels in the cortex, hypothalamus and thalamus were higher than those in the controls. In males exposed to BPA, the GABA levels in the amygdala and hippocampus showed lower values, while Glu levels were higher in some regions, compared with the controls. In regard to the associations, the number of "diurnal corner visits without drinking" was correlated with the NE levels in the cortex and thalamus in females. The "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus in males. These results suggest that prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA and Glu systems, resulting in behavioral alterations. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Developmental programming: interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep

PubMed Central

Koneva, LA; Vyas, AK; McEachin, RC; Puttabyatappa, M; H-S, Wang; Sartor, MA; Padmanabhan, V

2017-01-01

Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85–141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. PMID:28079927

Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts.

PubMed

Huang, Y Q; Wong, C K C; Zheng, J S; Bouwman, H; Barra, R; Wahlström, B; Neretin, L; Wong, M H

2012-07-01

Bisphenol A (BPA), identified as an endocrine disruptor, is an industrially important chemical that is used as a raw material in the manufacture of many products such as engineering plastics (e.g., epoxy resins/polycarbonate plastics), food cans (i.e., lacquer coatings), and dental composites/sealants. The demand and production capacity of BPA in China have grown rapidly. This trend will lead to much more BPA contamination in the environmental media and in the general population in China. This paper reviews the current literature concerning the pollution status of BPA in China (the mainland, Hong Kong, and Taiwan) and its potential impact on human health. Due to potential human health risks from long-term exposure to BPA, body burden of the contaminant should be monitored. Copyright © 2011 Elsevier Ltd. All rights reserved.

Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.

PubMed

Koneva, L A; Vyas, A K; McEachin, R C; Puttabyatappa, M; Wang, H-S; Sartor, M A; Padmanabhan, V

2017-01-01

Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaoxia, E-mail: Xiaoxia.Yang@fda.hhs.gov; Doerge, Daniel R.; Fisher, Jeffrey W.

Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled withmore » serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100 μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in young and adult rats. • BPA metabolism within enterocytes is required for fitting of oral BPA kinetic data. • BPA dosimetry in young rats is different than adult rats and young monkeys.« less

Comparison of the effects of BPA and BPAF on oocyte spindle assembly and polar body release in mice.

PubMed

Nakano, Kei; Nishio, Manami; Kobayashi, Norio; Hiradate, Yuuki; Hoshino, Yumi; Sato, Eimei; Tanemura, Kentaro

2016-04-01

Bisphenol AF (BPAF), a homolog of bisphenol A (BPA), is a widely used environmental chemical that has adverse effects on reproduction. The aim of this study was to analyse the effects of BPA and BPAF exposure on oocyte maturation in vitro. Oocytes were cultured in the presence of BPA or BPAF (2, 20, 50 or 100 μg/ml) for 18 h. At concentrations of 50 and 100 μg/ml, BPA and BPAF inhibited oocyte maturation, with BPAF treatment causing a sharp decrease in the number of oocytes reaching maturity. Oocytes were exposed to BPA or BPAF at 2 μg/ml and cultured for different durations (6, 9, 12, 15 or 18 h). Both BPAF and BPA caused a cell cycle delay under these conditions. Oocytes cultured in the presence of BPA or BPAF (50 μg/ml) for 21 h were tested for the localization of α-tubulin and MAD2 using immunofluorescence. High concentrations of BPAF induced cell cycle arrest through the activation of the spindle assembly checkpoint. After 12 h of culture in BPAF (50 μg/ml), oocytes were transferred to control medium for 9 h. Only 63.3% oocytes treated in this manner progressed to metaphase II (MII). Oocytes exposed to high doses of BPA experienced a cell cycle delay, but managed to progress to MII when the culture period was prolonged. In addition, MAD2 was localized in the cytoplasm of these oocytes. In conclusion, both BPAF and BPA exposure affected oocyte maturation, however BPAF and BPA have differential effects on SAC activity.

Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat.

PubMed

Zaid, Siti Sarah Mohamad; Othman, Shatrah; Kassim, Normadiah M

2014-12-17

To investigate the potential protective effects of Tualang honey against the toxicity effects induced by Bisphenol A (BPA) on pubertal development of ovaries. This study was conducted on pre-pubertal female Sprague Dawley rats. Animals were divided into four groups (n = 8 in each group). Group I was administered with vehicle 0.2 ml of corn oil (Sigma-Aldrich, USA) using oral gavage daily for six weeks; these animals served as negative control (CO group), Group II was administered with BPA suspended in corn oil at 10 mg/kg body weight and served as positive control (PC group), Group III was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of BPA at 10 mg/kg (TH group) while Group IV was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of corn oil (THC group). Body weight of all animals were monitored weekly. The BPA-exposed animals exhibited disruption of their estrus cycle, while those animals treated with BPA together with Tualang honey, exhibited an improvement in percentage of normal estrous cycle. Their ovaries had lower numbers of atretic follicles compared to the PC group but higher than the CO group. Tualang honey has a potential role in reducing BPA-induced ovarian toxicity by reducing the morphological abnormalities of the ovarian follicles and improving the normal estrous cycle.

Impact of Gestational Bisphenol A on Oxidative Stress and Free Fatty Acids: Human Association and Interspecies Animal Testing Studies

PubMed Central

Veiga-Lopez, Almudena; Pennathur, Subramaniam; Kannan, Kurunthachalam; Patisaul, Heather B.; Dolinoy, Dana C.; Zeng, Lixia

2015-01-01

Bisphenol A (BPA) is a high production volume chemical and an endocrine disruptor. Developmental exposures to BPA have been linked to adult metabolic pathologies, but the pathways through which these disruptions occur remain unknown. This is a comprehensive interspecies association vs causal study to evaluate risks posed by prenatal BPA exposure and to facilitate discovery of biomarkers of relevance to BPA toxicity. Samples from human pregnancies during the first trimester and at term, as well as fetal and/or adult samples from prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact of BPA on free fatty acid and oxidative stress dynamics. Mothers exposed to higher BPA during early to midpregnancy and their matching term cord samples displayed increased 3-nitrotyrosine (NY), a marker of nitrosative stress. Maternal samples had increased palmitic acid, which was positively correlated with NY. Sheep fetuses and adult sheep and rats prenatally exposed to a human-relevant exposure dose of BPA showed increased systemic nitrosative stress. The strongest effect of BPA on circulating free fatty acids was observed in adult mice in the absence of increased oxidative stress. This is the first multispecies study that combines human association and animal causal studies assessing the risk posed by prenatal BPA exposure to metabolic health. This study provides evidence of the induction of nitrosative stress by prenatal BPA in both the mother and fetus at time of birth and is thus supportive of the use of maternal NY as a biomarker for offspring health. PMID:25603046

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

PubMed

Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

PubMed Central

Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

Cu-PDC-bpa solid coordination frameworks (PDC=2,5-pyrindinedicarboxylate; bpa=1,2-DI(4-pyridil)ethane)): 2D and 3D structural flexibility producing a 3-c herringbone array next to ideal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Llano-Tomé, Francisco, E-mail: francisco.llano@ehu.eus; Bazán, Begoña, E-mail: bego.bazan@ehu.eus; BCMaterials Parque Tecnológico de Zamudio, Ibaizabal Bidea, Edificio 500–Planta 1, 48160 Derio

Combination of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce solid coordination frameworks (SCF) which are crystalline materials based on connections between metal ions through organic ligands. In this context, this work is focused on two novel Cu{sup II}-based SCFs exhibiting PDC (2,5-pyridinedicarboxylate) and bpa (1,2-di(4-pyridyl)ethane), being the first structures reported in literature containing both ligands. Chemical formula are [Cu{sub 2}[(PDC){sub 2}(bpa)(H{sub 2}O){sub 2}]·3H{sub 2}O·DMF (1), and [Cu{sub 2}(PDC){sub 2}(bpa)(H{sub 2}O){sub 2}]·7H{sub 2}O (2), where DMF is dimethylformamide. Compounds 1 and 2 have been characterized by means of X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric (TG) analysis,more » differential thermal analysis (DTA) and dielectric measurements. The crystallographic analysis revealed that compounds 1 and 2 can be described as herringbone-type layers formed by helicoidal Cu-PDC-Cu chains connected through bpa ligands. Solvent molecules are crystallized between the layers, providing the inter-layer connections through hydrogen bonds. Differences between both compounds are attributable to the flexibility of bpa (in 2D) as well as to the 3D packing of the layers which is solvent dependent. This fact results in the fact that compound 2 is the most regular 3-c herringbone array reported so far. The structural dynamism of these networks is responsible for the crystalline to-amorphous to-crystalline (CAC) transformation from compound 1 to compound 2. Crystallochemical features for both compounds have also been studied and compared to similar 3-connected herringbone-arrays. - Graphical abstract: Cu-PDC-bpa 3-c herringbone arrays. - Highlights: • The most ideal herringbone array reported so far is a Cu-PDC-bpa SCF. • Conformational freedom of bpa results in 2D and 3D flexibility of the SCFs. • The flexibility of the SCFs is related to a phase transformation. �

Boron analysis for neutron capture therapy using particle-induced gamma-ray emission.

PubMed

Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

2015-12-01

The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

PubMed Central

Veiga-Lopez, A; Beckett, EM; Abi Salloum, B; Ye, W; Padmanabhan, V

2014-01-01

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. PMID:24923655

Quercus dilatata Lindl. ex Royle ameliorates BPA induced hepatotoxicity in Sprague Dawley rats.

PubMed

Kazmi, Syeda Tayyaba Batool; Majid, Muhammad; Maryam, Sonia; Rahat, Aymen; Ahmed, Madiha; Khan, Muhammad Rashid; Haq, Ihsan Ul

2018-06-01

Quercus dilatata Lindl. ex Royle was evaluated for in vitro polyphenol content and antioxidant potential as well as in vivo protective role against bisphenol A (BPA) induced hepatotoxicity. The distilled water-acetone (QDDAE) and methanol-ethyl acetate (QDMEtE) extracts were standardized and administered in high (300 mg/kg body weight (BW) and low (150 mg/kg BW) doses to Sprague Dawley rats, injected with BPA (25 mg/kg BW). Silymarin (50 mg/kg BW) was used as positive control. Subsequently, blood and liver homogenates were collected after four weeks of treatment, and the defensive effects of both extracts against oxidative damage and genotoxicity were assessed via hematological and biochemical investigations, determination of endogenous expression of enzymes as well as levels of free radicals and comet assay. Between the two extracts, maximum phenolics (213 ± 0.15 μg gallic acid equivalent/mg dry extract (DE) and flavonoids (55.6 ± 0.16 μg quercetin equivalent/mg DE) content, DPPH scavenging activity (IC 50 : 8.1 ± 0.5 μg/ml), antioxidant capacity (53.7 ± 0.98 μg ascorbic acid equivalent (AAE)/mg DE) and reducing potential (228.4 ± 2.4 μg AAE/mg DE) were observed in QDMEtE. In in vivo analysis, a dose dependent hepatoprotective activity was exhibited by both the extracts. QDDAE demonstrated maximum reduction in levels of alanine transaminase (49.77 ± 3.83 U/l), thiobarbituric acid reactant substances (33.46 ± 0.70 nM/min/mg protein), hydrogen peroxide (18.08 ± 0.01 ng/mg tissue) and nitrite (55.64 ± 1.79 μM/ml), along with decline in erythrocyte sedimentation rate (4.13 ± 0.072 mm/h), histopathological injuries and DNA damage in BPA intoxicated rats as compared with QDMEtE. Likewise, QDDAE also significantly restored activity levels of endogenous antioxidants, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (POD) and GSH with values of 6.46 ± 0.15�

Acid Rain, pH & Acidity: A Common Misinterpretation.

ERIC Educational Resources Information Center

Clark, David B.; Thompson, Ronald E.

1989-01-01

Illustrates the basis for misleading statements about the relationship between pH and acid content in acid rain. Explains why pH cannot be used as a measure of acidity for rain or any other solution. Suggests that teachers present acidity and pH as two separate and distinct concepts. (RT)

MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1.

PubMed

Wei, Jie; Ding, Dongxiao; Wang, Tao; Liu, Qiong; Lin, Yi

2017-12-01

Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/d) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 ( Pdx1 ) expression in mice. Inhibition of Pdx1 reduced glucose-stimulated insulin secretion and ATP production in the islets of BPA-exposed mice. Based on primary pancreatic islets, we also confirmed that miR-338 regulated Pdx1 and thus contributed to BPA-induced insulin secretory dysfunction from compensation to decompensation. Short-term BPA exposure downregulated miR-338 through activation of G-protein-coupled estrogen receptor 1 (Gpr30), whereas long-term BPA exposure upregulated miR-338 through suppression of glucagon-like peptide 1 receptor (Glp1r). Taken together, our results reveal a molecular mechanism, whereby BPA regulates Gpr30/Glp1r to mediate the expression of miR-338, which acts to control Pdx1-dependent insulin secretion. The Gpr30/Glp1r-miR-338-Pdx1 axis should be represented as a novel mechanism by which BPA induces insulin secretory dysfunction in pancreatic islets.-Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1. © FASEB.

Short-Term and Long-Term Effects of Bisphenol A (BPA) Exposure During Breastfeeding on the Biochemical and Endocrine Profiles in Rats.

PubMed

Santos-Silva, Ana P; de Moura, Egberto Gaspar; Pinheiro, Cintia R; Oliveira, Elaine; Lisboa, Patricia Cristina

2018-06-01

Neonates can be exposed to bisphenol A (BPA) through placenta and milk, and BPA is associated with disorders such as precocious puberty and obesity. We evaluated the effects of BPA exposure during breastfeeding on the biochemical and endocrine profiles in young and adult rat progeny. From postnatal day (PND) 3 to 15 dams were divided into low-dose BPA treatment [50 μg/kg/day s.c. (BPA-LD)], high-dose BPA treatment [5 mg/kg/day s.c. (BPA-HD)], and Control (vehicle) groups. Milk was collected at PND15 and 21, which represents the end of exposure and 6 days after withdrawal, respectively. Dams were euthanized at weaning. Offspring of both genders were euthanized at PND15, 21, and 180. Milk estradiol levels were lower in the BPA-HD group than in the control group at PND 15; however, they were higher at PND21. Female rats whose mothers were BPA-exposed showed more significant differences from those in the control group, including better glycemic control and lipid profiles and higher food intake without higher adiposity, in adulthood than in the weaning period, when they presented with higher adiposity and hyperestrogenism. Conversely, male rats showed more abnormalities after BPA exposure compared to control rats, including insulin, leptin, testosterone, and thyroid hormone changes, when young but exhibited fewer alterations in adulthood, with increase only in LDLc in the BPA-HD rats. Taken together, the present findings suggest that exposure to BPA exclusively through milk affects adiposity, metabolism, and/or hormones of offspring in the short and long term, possibly compromising normal development in both sexes. © Georg Thieme Verlag KG Stuttgart · New York.

48 CFR 339.7001 - Request for approval to make an award to other than a GSA BPA holder.

Code of Federal Regulations, 2010 CFR

2010-10-01

... make an award to other than a GSA BPA holder. 339.7001 Section 339.7001 Federal Acquisition Regulations... Services 339.7001 Request for approval to make an award to other than a GSA BPA holder. The Contracting... micro-purchase threshold, that obtaining the required services from a source other than a GSA BPA holder...

48 CFR 339.7001 - Request for approval to make an award to other than a GSA BPA holder.

Code of Federal Regulations, 2014 CFR

2014-10-01

... make an award to other than a GSA BPA holder. 339.7001 Section 339.7001 Federal Acquisition Regulations... Services 339.7001 Request for approval to make an award to other than a GSA BPA holder. The Contracting... micro-purchase threshold, that obtaining the required services from a source other than a GSA BPA holder...

48 CFR 339.7001 - Request for approval to make an award to other than a GSA BPA holder.

Code of Federal Regulations, 2011 CFR

2011-10-01

... make an award to other than a GSA BPA holder. 339.7001 Section 339.7001 Federal Acquisition Regulations... Services 339.7001 Request for approval to make an award to other than a GSA BPA holder. The Contracting... micro-purchase threshold, that obtaining the required services from a source other than a GSA BPA holder...

48 CFR 339.7001 - Request for approval to make an award to other than a GSA BPA holder.

Code of Federal Regulations, 2012 CFR

2012-10-01

... make an award to other than a GSA BPA holder. 339.7001 Section 339.7001 Federal Acquisition Regulations... Services 339.7001 Request for approval to make an award to other than a GSA BPA holder. The Contracting... micro-purchase threshold, that obtaining the required services from a source other than a GSA BPA holder...

48 CFR 339.7001 - Request for approval to make an award to other than a GSA BPA holder.

Code of Federal Regulations, 2013 CFR

2013-10-01

... make an award to other than a GSA BPA holder. 339.7001 Section 339.7001 Federal Acquisition Regulations... Services 339.7001 Request for approval to make an award to other than a GSA BPA holder. The Contracting... micro-purchase threshold, that obtaining the required services from a source other than a GSA BPA holder...

Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults.

PubMed

Mersha, Mahlet D; Patel, Bansri M; Patel, Dipen; Richardson, Brittany N; Dhillon, Harbinder S

2015-09-17

Bisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA. Experiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA. Building upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

PubMed

Fujimoto, T; Andoh, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Sonobe, H; Epstein, Alan L; Akisue, T; Kirihata, M; Kurosaka, M; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.

PubMed

Cetkovic-Cvrlje, Marina; Thinamany, Sinduja; Bruner, Kylie A

2017-12-01

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4 + T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats.

PubMed

Pozzi, Emiliano C C; Trivillin, Verónica A; Colombo, Lucas L; Monti Hughes, Andrea; Thorp, Silvia I; Cardoso, Jorge E; Garabalino, Marcela A; Molinari, Ana J; Heber, Elisa M; Curotto, Paula; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Schwint, Amanda E

2013-11-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For eachmore » rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.« less

CLARITY-BPA: Effects of chronic bisphenol A exposure on the immune system: Part 2 - Characterization of lymphoproliferative and immune effector responses by splenic leukocytes.

PubMed

Li, Jinpeng; Bach, Anthony; Crawford, Robert B; Phadnis-Moghe, Ashwini S; Chen, Weimin; D'Ingillo, Shawna; Kovalova, Natalia; Suarez-Martinez, Jose E; Zhou, Jiajun; Kaplan, Barbara L F; Kaminski, Norbert E

2018-03-01

Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory. To address the divergent findings surrounding BPA exposure, a comprehensive chronic treatment study of BPA was conducted in Sprague-Dawley rats, termed the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, our studies evaluated the effects of BPA on a broad range of immune function endpoints using spleen cells isolated from BPA or vehicle treated rats. This comprehensive assessment included measurements of lymphoproliferation in response to mitogenic stimuli, immunoglobulin production by B cells, and cellular activation of T cells, NK cells, monocytes, granulocytes, macrophages and dendritic cells. In total, 630 different measurements in BPA treated rats were performed of which 35 measurements were statistically different from vehicle controls. The most substantive alteration associated with BPA treatment was the augmentation of lymphoproliferation in response to pokeweed mitogen stimulations in 1 year old male rats, which was also observed in the reference estrogen ethinyl estradiol treated groups. With the exception of the aforementioned, the statistically significant changes associated with BPA treatment were mostly sporadic and not dose-dependent with only one out of five BPA dose groups showing a statistical difference. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and showed no persistent trend over the one-year time period

Impairment of learning and memory performances induced by BPA: Evidences from the literature of a MoA mediated through an ED.

PubMed

Mhaouty-Kodja, Sakina; Belzunces, Luc P; Canivenc, Marie-Chantal; Schroeder, Henri; Chevrier, Cécile; Pasquier, Elodie

2018-03-29

Many rodent studies and a few non-human primate data report impairments of spatial and non-spatial memory induced by exposure to bisphenol A (BPA), which are associated with neural modifications, particularly in processes involved in synaptic plasticity. BPA-induced alterations involve disruption of the estrogenic pathway as established by reversal of BPA-induced effects with estrogenic receptor antagonist or by interference of BPA with administered estradiol in ovariectomized animals. Sex differences in hormonal impregnation during critical periods of development and their influence on maturation of learning and memory processes may explain the sexual dimorphism observed in BPA-induced effects in some studies. Altogether, these data highly support the plausibility that alteration of learning and memory and synaptic plasticity by BPA is essentially mediated by disturbance of the estrogenic pathways. As memory function in humans involves similar signaling pathways, this mode of action of BPA has the potential to alter human cognitive abilities. Copyright © 2018. Published by Elsevier B.V.

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

PubMed Central

Wada, Yuki; Hirose, Katsumi; Harada, Takaomi; Sato, Mariko; Watanabe, Tsubasa; Anbai, Akira; Hashimoto, Manabu; Takai, Yoshihiro

2018-01-01

Abstract Boron neutron capture therapy (BNCT) can potentially deliver high linear energy transfer particles to tumor cells without causing severe damage to surrounding normal tissue, and may thus be beneficial for cases with characteristics of infiltrative growth, which need a wider irradiation field, such as glioblastoma multiforme. Hypoxia is an important factor contributing to resistance to anticancer therapies such as radiotherapy and chemotherapy. In this study, we investigated the impact of oxygen status on 10B uptake in glioblastoma cells in vitro in order to evaluate the potential impact of local hypoxia on BNCT. T98G and A172 glioblastoma cells were used in the present study, and we examined the influence of oxygen concentration on cell viability, mRNA expression of L-amino acid transporter 1 (LAT1), and the uptake amount of 10B-BPA. T98G and A172 glioblastoma cells became quiescent after 72 h under 1% hypoxia but remained viable. Uptake of 10B-BPA, which is one of the agents for BNCT in clinical use, decreased linearly as oxygen levels were reduced from 20% through to 10%, 3% and 1%. Hypoxia with <10% O2 significantly decreased mRNA expression of LAT1 in both cell lines, indicating that reduced uptake of 10B-BPA in glioblastoma in hypoxic conditions may be due to reduced expression of this important transporter protein. Hypoxia inhibits 10B-BPA uptake in glioblastoma cells in a linear fashion, meaning that approaches to overcoming local tumor hypoxia may be an effective method of improving the success of BNCT treatment. PMID:29315429

Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression.

PubMed

Vahdati Hassani, Faezeh; Mehri, Soghra; Abnous, Khalil; Birner-Gruenberger, Ruth; Hosseinzadeh, Hossein

2017-09-01

Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemical and commonly used as a monomer of polycarbonate plastics and epoxy resins. The aim of the present study is to investigate the hepatoprotective effects of crocin, a constituent of saffron, against BPA-induced liver toxicity. We showed that treatment of male Wistar rats with 0.5 mg/kg BPA for 30 days increased the level of 8-isoprostane, decreased the level of reduced glutathione, elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, triglyceride, and glucose, and induced periportal inflammation. Western blot results revealed that BPA increased the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), and mitogen-activated protein kinase-activated protein kinase (MAPKAPK), but not p38. BPA also reduced the Akt signaling activation and upregulated microRNA (miR-122) expression. Moreover, we showed here that crocin 20 mg/kg administration ameliorated liver damage and improved elevated levels of TG and liver enzymes of BPA-treated rats possibly though antioxidant activity, downregulation of miR-122 transcript level and lowering the phosphorylation of JNK, ERK1/2, and MAPKAPK and subsequently their activities. Overall, the findings suggest that crocin possesses hepatoprotective effects against BPA-induced liver toxicity by enhancing the antioxidative defense system and regulation of important signaling pathway activities and miR-122 expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alteration of sensitivity of intratumor quiescent and total cells to gamma-rays following thermal neutron irradiation with or without 10B-compound.

PubMed

Masunaga, S; Ono, K; Suzuki, M; Sakurai, Y; Kobayashi, T; Takagaki, M; Kinashi, Y; Akaboshi, M

2000-02-01

Changes in the sensitivity of intratumor quiescent (Q) and total cells to gamma-rays following thermal neutron irradiation with or without 10B-compound were examined. 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of gamma-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. In total cells, during the interval between the two irradiations, the tumor sensitivity to gamma-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA. The longer the interval between the two irradiations, the higher was the BrdU-labeled cell

Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation

PubMed Central

McCaffrey, Katherine A.; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H.; Patisaul, Heather B.

2013-01-01

Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000 mg/kg bw/day BPA through daily, noninvasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day can alter sex specific hypothalamic morphology in the rat. PMID:23500335

Differential in Vitro Biological Action, Coregulator Interactions, and Molecular Dynamic Analysis of Bisphenol A (BPA), BPAF, and BPS Ligand-ERα Complexes.

PubMed

Li, Yin; Perera, Lalith; Coons, Laurel A; Burns, Katherine A; Tyler Ramsey, J; Pelch, Katherine E; Houtman, René; van Beuningen, Rinie; Teng, Christina T; Korach, Kenneth S

2018-01-31

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that might be harmful to human health. Recently, there has been widespread usage of bisphenol chemicals (BPs), such as bisphenol AF (BPAF) and bisphenol S (BPS), as replacements for BPA. However, the potential biological actions, toxicity, and the molecular mechanism of these compounds are still poorly understood. Our objective was to examine the estrogenic effects of BPA, BPAF, and BPS and the molecular mechanisms of action in the estrogen receptor alpha (ERα) complex. In vitro cell models were used to compare the estrogenic effects of BPA, BPAF, and BPS to estrogen. Microarray Assay for Real-Time Coregulator-Nuclear receptor Interaction (MARCoNI) analysis was used to identify coregulators of BPA, BPAF, and BPS, and molecular dynamic (MD) simulations were used to determine the compounds binding in the ERα complex. We demonstrated that BPA and BPAF have agonistic activity for both ERα and ERβ, but BPS has ERα-selective specificity. We concluded that coregulators were differentially recruited in the presence of BPA, BPAF, or BPS. Interestingly, BPS recruited more corepressors when compared to BPA and BPAF. From a series of MD analysis, we concluded that BPA, BPAF, and BPS can bind to the ER-ligand-binding domain with differing energetics and conformations. In addition, the binding surface of coregulator interactions on ERα was characterized for the BPA, BPAF, and BPS complexes. These findings further our understanding of the molecular mechanisms of EDCs, such as BPs, in ER-mediated transcriptional activation, biological activity, and their effects on physiological functions in human health. https://doi.org/10.1289/EHP2505.

In vivo spatial correlation between (18)F-BPA and (18)F-FDG uptakes in head and neck cancer.

PubMed

Kobayashi, Kazuma; Kurihara, Hiroaki; Watanabe, Yoshiaki; Murakami, Naoya; Inaba, Koji; Nakamura, Satoshi; Wakita, Akihisa; Okamoto, Hiroyuki; Umezawa, Rei; Takahashi, Kana; Igaki, Hiroshi; Ito, Yoshinori; Yoshimoto, Seiichi; Shigematsu, Naoyuki; Itami, Jun

2016-09-01

Borono-2-(18)F-fluoro-phenylalanine ((18)F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while (18)F-fluorodeoxyglucose ((18)F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between (18)F-BPA and (18)F-FDG uptakes using a deformable image registration-based technique. Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body (18)F-BPA PET/computed tomography (CT) and (18)F-FDG PET/CT within a 2-week period. For each patient, (18)F-BPA PET/CT and (18)F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between (18)F-BPA and (18)F-FDG showed a significant, positive correlation in the tumor volume. Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between (18)F-BPA and (18)F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high (18)F-FDG uptake may predict high accumulation of (18)F-BPA. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor.

PubMed

Bremer, A A; Leeman, S E; Boyd, N D

2000-12-01

Although neurokinin A (NKA), a tachykinin peptide with sequence homology to substance P (SP), is a weak competitor of radiolabeled SP binding to the NK-1 receptor (NK-1R), more recent direct binding studies using radiolabeled NKA have demonstrated an unexpected high-affinity interaction with this receptor. To document the site of interaction between NKA and the NK-1R, we have used a photoreactive analogue of NKA containing p-benzoyl-L-phenylalanine (Bpa) substituted in position 7 of the peptide. Peptide mapping studies of the receptor photolabeled by (125)I-iodohistidyl(1)-Bpa(7)NKA have established that the site of photoinsertion is located within a segment of the receptor extending from residues 178 to 190 (VVCMIEWPEHPNR). We have previously shown that (125)I-BH-Bpa(8)SP, a photoreactive analogue of SP, covalently attaches to M(181) within this same receptor sequence. Importantly, both of these peptides ((125)I-iodohistidyl(1)-Bpa(7)NKA and (125)I-BH-Bpa(8)SP) have the photoreactive amino acid in an equivalent position within the conserved tachykinin carboxyl-terminal tail. In this report, we also show that site-directed mutagenesis of M(181) to A(181) in the NK-1R results in a complete loss of photolabeling of both peptides to this receptor site, indicating that the equivalent position of SP and NKA, when bound to the NK-1R, contact the same residue.

Multifunctional data acquisition and analysis and optical sensors: a Bonneville Power Administration (BPA) update

NASA Astrophysics Data System (ADS)

Erickson, Dennis C.; Donnelly, Matt K.

1995-04-01

The authors present a design concept describing a multifunctional data acquisition and analysis architecture for advanced power system monitoring. The system is tailored to take advantage of the salient features of low energy sensors, particularly optical types. The discussion of the system concept and optical sensors is based on research at BPA and PNL and on progress made at existing BPA installations and other sites in the western power system.

Assessing the concentration of phthalate esters (PAEs) and bisphenol A (BPA) and the genotoxic potential of treated wastewater (final effluent) in Saudi Arabia.

PubMed

Al-Saleh, Iman; Elkhatib, Rola; Al-Rajoudi, Tahreer; Al-Qudaihi, Ghofran

2017-02-01

Plasticizers such as phthalate esters (PAEs) and bisphenol A (BPA) are highly persistent organic pollutants that tend to bio-accumulate in humans through the soil-plant-animal food chain. Some studies have reported the potential carcinogenic and teratogenic effects in addition to their estrogenic activities. Water resources are scarce in Saudi Arabia, and several wastewater treatment plants (WTPs) have been constructed for agricultural and industrial use. This study was designed to: (1) measure the concentrations of BPA and six PAEs, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP) and dioctyl phthalate (DOP), in secondary- and tertiary-treated wastewater collected from five WTPs in three Saudi cities for four to five weeks and (2) test their potential genotoxicity. Three genotoxicological parameters were used: % tail DNA (%T), tail moment (TM) and percentage micronuclei (%MN). Both DBP and DEHP were detected in all treated wastewater samples. DMP, DEP, BBP, DOP, and BPA were found in 83.3, 84.2, 79, 73.7 and 97.4% of the samples, respectively. The levels of DMP (p<0.001), DOP (p<0.001) and BPA (p=0.001) were higher in tertiary- treated wastewater than secondary-treated wastewater, perhaps due to the influence of the molecular weight and polarity of the chemicals. Both weekly sampling frequency and WTP locations significantly affected the variability in our data. Treated wastewater from Wadi Al-Araj was able to induce DNA damage (%T and TM) in human lymphoblastoid TK6 cells that was statistically higher than wastewater from all other WTPs and in untreated TK6 cells (negative control). %MN in samples from both Wadi Al-Araj and Manfouah did not differ statistically but was significantly higher than in the untreated TK6 cells. This study also showed that the samples of tertiary-treated wastewater had a higher genotoxicological potential to induce DNA damage than the samples of

Exposure assessment of adult intake of bisphenol A (BPA) with emphasis on canned food dietary exposures.

PubMed

Lorber, Matthew; Schecter, Arnold; Paepke, Olaf; Shropshire, William; Christensen, Krista; Birnbaum, Linda

2015-04-01

Bisphenol A (BPA) is a high-volume, synthetic compound found in epoxy resins and plastics used in food packaging. Food is believed to be a major source of BPA intake. In this study, we measured the concentration of BPA in convenience samplings of foodstuffs purchased in Dallas, Texas. Sampling entailed collection of 204 samples of fresh, frozen, and canned foods in two rounds in 2010. BPA was positive in 73% of the canned food samples, while it was found in only 7% of non-canned foods at low concentrations. The results of this food sampling program were used to calculate adult dietary intakes of BPA. A pathway approach combined food intakes, a "canned fraction" parameter which described what portion of total intake of that food came from canned products, and measured food concentrations. Dietary intakes were calculated as 12.6 ng/kg-day, of which 12.4 ng/kg-day was from canned foods. Canned vegetable intakes alone were 11.9 ng/kg-day. This dietary intake was compared to total intakes of BPA estimated from urine measurements of the National Health and Nutrition Examination Survey (NHANES). Total adult central tendency intakes ranged from 30 to 70 ng/kg-day for NHANES cycles between 2005 and 2010. Three possibilities were explored to explain the difference between these two approaches for intake estimation. Not all foods which may have been canned, particularly canned beverages such as soft drinks, were sampled in our food sampling program. Second, non-food pathways of exposure may be important for adults, including thermal paper exposures, and dust and air exposures. Finally, our canned food concentrations may not be adequately representative of canned foods in the United States; they were found to be generally lower compared to canned food concentrations measured in six other worldwide food surveys including three in North America. Our finding that canned food concentrations greatly exceeded non-canned concentrations was consistent with other studies, and

Enhanced uptake of BPA in the presence of nanoplastics can lead to neurotoxic effects in adult zebrafish.

PubMed

Chen, Qiqing; Yin, Daqiang; Jia, Yunlu; Schiwy, Sabrina; Legradi, Jessica; Yang, Shouye; Hollert, Henner

2017-12-31

Plastic particles have been proven to be abundant in the aquatic environment, raising concerns about their potential toxic effects. In the present study, we determined the bioaccumulation potential of bisphenol A (BPA) in adult zebrafish (Danio rerio) in the absence and presence of nano-sized plastic particles (nanoplastics, NPPs). Results show that BPA can accumulate in the viscera, gill, head and muscle of zebrafish with 85, 43, 20, and 3μg/g ww after 1d exposure. NPPs were also found to accumulate in different tissues of the fish. Relative equilibrium was reached after 1d exposure in different tissues with 39 to 636mg/kg ww. Co-exposure of NPPs and BPA led to a 2.2 and 2.6-fold significant increment of BPA uptake in the head and viscera, if compared with BPA alone treatment after 3d exposure. As such, we further investigated several neurotoxic biomarker alterations in the fish head. It was found that either BPA or NPPs can cause myelin basic protein (MBP)/gene up-regulation in the central nervous system (CNS); meanwhile, both contaminants exhibited significant inhibition of acetylcholinesterase (AChE) activity, which is a well-known representative biomarker for neurotoxicity. Moreover, for the co-exposure treatment, biomarkers of myeline and tubulin protein/gene expressions, dopamine content, and the mRNA expression of mesencephalic astrocyte derived neurotrophic factor (MANF) were all significantly up-regulated, suggesting that an enhanced neurotoxic effects in both CNS and dopaminergic system occurred. However, AChE activity was no more inhibited in the co-exposure treatment, which implies that solely AChE measurement may not be sufficient to identify neurotoxic effects in the cholinergic system. Overall, the present study demonstrates that the presence of NPPs can increase BPA bioavailability and cause neurotoxicity in adult zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation.

PubMed

McCaffrey, Katherine A; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H; Patisaul, Heather B

2013-05-01

Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000μg/kg bw/day BPA through daily, non-invasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50mg/kg/day can alter sex specific hypothalamic morphology in the rat. Copyright © 2013 Elsevier Inc. All rights reserved.

Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

PubMed Central

Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: a LC-QTOF-based metabolomics study.

PubMed

Chen, Minjian; Xu, Bin; Ji, Wenliang; Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

2012-01-01

Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.

Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-06-21

Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. Associations between in utero

Impact of bisphenol A (BPA) on early embryo development in the marine mussel Mytilus galloprovincialis: Effects on gene transcription.

PubMed

Balbi, Teresa; Franzellitti, Silvia; Fabbri, Rita; Montagna, Michele; Fabbri, Elena; Canesi, Laura

2016-11-01

Bisphenol A (BPA), a monomer used in plastic manufacturing, is weakly estrogenic and a potential endocrine disruptor in mammals. Although it degrades quickly, it is pseudo-persistent in the environment because of continual inputs, with reported concentrations in aquatic environments between 0.0005 and 12 μg/L. BPA represents a potential concern for aquatic ecosystems, as shown by its reproductive and developmental effects in aquatic vertebrates. In invertebrates, endocrine-related effects of BPA were observed in different species and experimental conditions, with often conflicting results, indicating that the sensitivity to this compound can vary considerably among related taxa. In the marine mussel Mytilus galloprovincialis BPA was recently shown to affect early development at environmental concentrations. In this work, the possible effects of BPA on mussel embryos were investigated at the molecular level by evaluating transcription of 13 genes, selected on the basis of their biological functions in adult mussels. Gene expression was first evaluated in trocophorae and D-veligers (24 and 48 h post fertilization) grown in physiological conditions, in comparison with unfertilized eggs. Basal expressions showed a general up-regulation during development, with distinct transcript levels in trocophorae and D-veligers. Exposure of fertilized eggs to BPA (10 μg/L) induced a general upregulation at 24 h pf, followed by down regulation at 48 h pf. Mytilus Estrogen Receptors, serotonin receptor and genes involved in biomineralization (Carbonic Anydrase and Extrapallial Protein) were the most affected by BPA exposure. At 48 h pf, changes in gene expression were associated with irregularities in shell formation, as shown by scanning electron microscopy (SEM), indicating that the formation of the first shelled embryo, a key step in mussel development, represents a sensitive target for BPA. Similar results were obtained with the natural estrogen 17β-estradiol. The

Microarray expression profiling and co-expression network analysis of circulating LncRNAs and mRNAs associated with neurotoxicity induced by BPA.

PubMed

Pang, Wei; Lian, Fu-Zhi; Leng, Xue; Wang, Shu-Min; Li, Yi-Bo; Wang, Zi-Yu; Li, Kai-Ren; Gao, Zhi-Xian; Jiang, Yu-Gang

2018-05-01

A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151 differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis, injury, and neuroinflammation responses. In the expression network of the BPA-induced group, a great number of nodes and connections were found in comparison to the control-derived network. We identified lncRNAs that were aberrantly expressed in the BPA group, among which, growth arrest specific 5 (GAS5) might participate in the BPA-induced neurotoxicity by regulating Jun, RAS, and other pathways indirectly through these differentially expressed genes. This study provides the first investigation of genome-wide lncRNA expression and correlation between lncRNA and mRNA expression in the BPA-induced neurotoxicity. Our results suggest that the elevated expression of lncRNAs is a major biomarker in the neurotoxicity induced by BPA.

Cu-PDC-bpa solid coordination frameworks (PDC=2,5-pyrindinedicarboxylate; bpa=1,2-DI(4-pyridil)ethane)): 2D and 3D structural flexibility producing a 3-c herringbone array next to ideal

NASA Astrophysics Data System (ADS)

Llano-Tomé, Francisco; Bazán, Begoña; Urtiaga, Miren-Karmele; Barandika, Gotzone; Antonia Señarís-Rodríguez, M.; Sánchez-Andújar, Manuel; Arriortua, María-Isabel

2015-10-01

Combination of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce solid coordination frameworks (SCF) which are crystalline materials based on connections between metal ions through organic ligands. In this context, this work is focused on two novel CuII-based SCFs exhibiting PDC (2,5-pyridinedicarboxylate) and bpa (1,2-di(4-pyridyl)ethane), being the first structures reported in literature containing both ligands. Chemical formula are [Cu2[(PDC)2(bpa)(H2O)2]·3H2O·DMF (1), and [Cu2(PDC)2(bpa)(H2O)2]·7H2O (2), where DMF is dimethylformamide. Compounds 1 and 2 have been characterized by means of X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric (TG) analysis, differential thermal analysis (DTA) and dielectric measurements. The crystallographic analysis revealed that compounds 1 and 2 can be described as herringbone-type layers formed by helicoidal Cu-PDC-Cu chains connected through bpa ligands. Solvent molecules are crystallized between the layers, providing the inter-layer connections through hydrogen bonds. Differences between both compounds are attributable to the flexibility of bpa (in 2D) as well as to the 3D packing of the layers which is solvent dependent. This fact results in the fact that compound 2 is the most regular 3-c herringbone array reported so far. The structural dynamism of these networks is responsible for the crystalline to-amorphous to-crystalline (CAC) transformation from compound 1 to compound 2. Crystallochemical features for both compounds have also been studied and compared to similar 3-connected herringbone-arrays.

Holding Thermal Receipt Paper and Eating Food after Using Hand Sanitizer Results in High Serum Bioactive and Urine Total Levels of Bisphenol A (BPA)

PubMed Central

Hormann, Annette M.; vom Saal, Frederick S.; Nagel, Susan C.; Stahlhut, Richard W.; Moyer, Carol L.; Ellersieck, Mark R.; Welshons, Wade V.; Toutain, Pierre-Louis; Taylor, Julia A.

2014-01-01

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults. PMID:25337790

Holding thermal receipt paper and eating food after using hand sanitizer results in high serum bioactive and urine total levels of bisphenol A (BPA).

PubMed

Hormann, Annette M; Vom Saal, Frederick S; Nagel, Susan C; Stahlhut, Richard W; Moyer, Carol L; Ellersieck, Mark R; Welshons, Wade V; Toutain, Pierre-Louis; Taylor, Julia A

2014-01-01

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.

Visualizing BPA by molecularly imprinted ratiometric fluorescence sensor based on dual emission nanoparticles.

PubMed

Lu, Hongzhi; Xu, Shoufang

2017-06-15

Construction of ratiometric fluorescent probe often involved in tedious multistep preparation or complicated coupling or chemical modification process. The emergence of dual emission fluorescent nanoparticles would simplify the construction process and avoids the tedious chemical coupling. Herein, we reported a facile strategy to prepare ratiometric fluorescence molecularly imprinted sensor based on dual emission nanoparticles (d-NPs) which comprised of carbon dots and gold nanoclusters for detection of Bisphenol A (BPA). D-NPs emission at 460nm and 580nm were first prepared by seed growth co-microwave method using gold nanoparticles as seeds and glucose as precursor for carbon dots. When they were applied to propose ratiometric fluorescence molecularly imprinted sensor, the preparation process was simplified, and the sensitivity of sensor was improved with detection limit of 29nM, and visualizing BPA was feasible based on the distinguish fluorescence color change. The feasibility of the developed method in real samples was successfully evaluated through the analysis of BPA in water samples with satisfactory recoveries of 95.9-98.9% and recoveries ranging from 92.6% to 98.6% in canned food samples. When detection BPA in positive feeding bottles, the results agree well with those obtained by accredited method. The developed method proposed in this work to prepare ratiometric fluorescence molecularly imprinted sensor based on dual emission nanoparticles proved to be a convenient, reliable and practical way to prepared high sensitive and selective fluorescence sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

The photophysics of fac-[Re(CO)3(NN)(bpa)](+) complexes: a theoretical/experimental study.

PubMed

Sousa, S F; Sampaio, R N; Barbosa Neto, N M; Machado, A E H; Patrocinio, A O T

2014-08-01

The influence of the polypyridyl ligand on the photophysics of fac-[Re(CO)3(NN)(bpa)](+), bpa = 1,2-bis-(4-pyridyl)ethane and NN = 1,10-phenanthroline (phen), pyrazino[2,3-f][1,10]-phenanthroline (dpq), and dipyrido[3,2-a:2'3'-c]phenazine (dppz) has been investigated by steady state and time-resolved emission spectroscopy combined with theoretical calculations using time-dependent density functional theory (TD-DFT). The fac-[Re(CO)3(phen)(bpa)](+) is a typical MLCT emitter in acetonitrile with ϕ = 0.11 and τ = 970 ns. The emission lifetime and quantum yield decrease significantly in fac-[Re(CO)3(dpq)(bpa)](+) (ϕ = 0.05; τ = 375 ns) due to the presence of a close lying dark charge transfer state located at the pyrazine ring of dpq, as indicated by TD-DFT data. The luminescence of these complexes is quenched by hydroquinone with kq = (2.9 ± 0.1) × 10(9) and (2.6 ± 0.1) × 10(9) L mol(-1) s(-1), respectively, for NN = phen or dpq. These values are increased respectively to (4.6 ± 0.1) × 10(9) and (4.2 ± 0.1) × 10(9) L mol(-1) s(-1) in the 1 : 1 H2O-CH3CN mixture. In this medium Stern-Volmer constants determined by steady-state and time-resolved measurements differ from each other, which is indicative of static quenching, i.e. the pre-association of hydroquinone and the complexes through hydrogen bonding between the remote N-atom in the bpa ligand (KA ≅ 1-2 × 10(1) L mol(-1)), followed by a concerted proton-electron transfer. In contrast to other investigated complexes, fac-[Re(CO)3(dppz)(bpa)](+) is weakly emissive in acetonitrile at room temperature (ϕ ≅ 10(-4)) and does not exhibit a rigidochromic effect. This photophysical behaviour as well as TD-DFT data indicate that the lowest lying triplet excited state can be described as (3)ILdppz. The results provide additional insight into the influence of the polypyridyl ligand on the photophysical properties of Re(I) complexes.

Prenatal exposure estimation of BPA and DEHP using integrated external and internal dosimetry: A case study.

PubMed

Martínez, M A; Rovira, J; Sharma, R Prasad; Nadal, M; Schuhmacher, M; Kumar, V

2017-10-01

Prenatal exposure to Endocrine disruptors (EDs), such as Bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP), has been associated with obesity and diabetes diseases in childhood, as well as reproductive, behavioral and neurodevelopment problems. The aim of this study was to estimate the prenatal exposure to BPA and DEHP through food consumption for pregnant women living in Tarragona County (Spain). Probabilistic calculations of prenatal exposure were estimated by integrated external and internal dosimetry modelling, physiologically based pharmacokinetic (PBPK) model, using a Monte-Carlo simulation. Physical characteristic data from the cohort, along with food intake information from the questionnaires (concentrations of BPA and DEHP in different food categories and the range of the different food ratios), were used to estimate the value of the total dietary intake for the Tarragona pregnancy cohort. The major contributors to the total dietary intake of BPA were canned fruits and vegetables, followed by canned meat and meat products. In turn, milk and dairy products, followed by ready to eat food (including canned dinners), were the most important contributors to the total dietary intake of DEHP. Despite the dietary variations among the participants, the intakes of both chemicals were considerably lower than their respective current tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Internal dosimetry estimates suggest that the plasma concentrations of free BPA and the most important DEHP metabolite, mono (2-ethylhexyl) phthalate (MEHP), in pregnant women were characterized by transient peaks (associated with meals) and short half-lives (< 2h). In contrast, fetal exposure was characterized by a low and sustained basal BPA and MEHP concentration due to a lack of metabolic activity in the fetus. Therefore, EDs may have a greater effect on developing organs in young children or in the unborn child. Copyright © 2017

In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish-specific assays.

PubMed

Le Fol, Vincent; Aït-Aïssa, Selim; Sonavane, Manoj; Porcher, Jean-Marc; Balaguer, Patrick; Cravedi, Jean-Pierre; Zalko, Daniel; Brion, François

2017-08-01

Bisphenol A (BPA) is a widely used chemical that has been extensively studied as an endocrine-disrupting chemical (EDC). Other bisphenols sharing close structural features with BPA, are increasingly being used as alternatives, increasing the need to assess associated hazards to the endocrine system. In the present study, the estrogenic activity of BPA, bisphenol S (BPS) and bisphenol F (BPF) was assessed by using a combination of zebrafish-specific mechanism-based in vitro and in vivo assays. The three bisphenols were found to efficiently transactivate all zebrafish estrogen receptor (zfER) subtypes in zebrafish hepatic reporter cell lines (ZELH-zfERs). BPA was selective for zfERα while BPS and BPF were slightly more potent on zfERβ subtypes. We further documented the estrogenic effect in vivo by quantifying the expression of brain aromatase using a transgenic cyp19a1b-GFP zebrafish embryo assay. All three bisphenols induced GFP in a concentration-dependent manner. BPS only partially induced brain aromatase at the highest tested concentrations (>30µM) while BPA and BPF strongly induced GFP, in an ER-dependent manner, at 1-10µM. Furthermore, we show that BPF strongly induced vitellogenin synthesis in adult male zebrafish. Overall, this study demonstrates the estrogenic activity of BPA, BPF and BPS in different cell- and tissue-contexts and at different stages of development. Differences between in vitro and in vivo responses are discussed in light of selective ER activation and the fate of the compounds in the models. This study confirms the relevance of combining cellular and whole-organism bioassays in a unique model species for the hazard assessment of candidate EDCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Brevibacillus brevis FJAT-1501-BPA on growth performance, faecal microflora, faecal enzyme activities and blood parameters of weaned piglets.

PubMed

Che, Jianmei; Ye, Shaowen; Liu, Bo; Deng, Yuanyuan; Chen, Qianqian; Ge, Cibin; Liu, Guohong; Wang, Jieping

2016-12-01

A feeding expriment was performed to investigate the effects of dietary supplementation with Brevibacillus brevis FJAT-1501-BPA fermentation on the growth performance, faecal microflora, faecal enzyme activities and blood parameters of weaned piglets. A total of 150 weaned piglets were randomly assigned to different treatments groups, which were fed the same basic diet supplemented with 10, 1, 0.1, 0.01 and 0 % B. brevis FJAT-1501-BPA fermentation. The results showed that a diet supplemented with 10 % B. brevis FJAT-1501-BPA fermentation could significantly increase the final body weight (P < 0.05) and decrease feed to gain ratio, which was 37.1 % lower than that of the control group. The addition of B. brevis FJAT-1501-BPA exhibited a trend of reducing the contents of the Escherichia coli, Lactobacillus and Salmonella compared with the control. During the 35 day experimental period, cellulase and protease activities were significantly increased by the dietary inclusion of the B. brevis FJAT-1501-BPA fermentation (P < 0.05). The cellulase activity for piglets fed diet containing 1 % B. brevis FJAT-1501-BPA fermentation, 21.8 U/g, was highest among the different treatments. The protease activity for piglets fed diet containing 10 % B. brevis FJAT-1501-BPA fermentation, 50.4 U/g, was highest among the different treatments. The amylase and hemicellulase activities for piglets fed diet containing 10 % B. brevis FJAT-1501-BPA fermentation were significantly higher than those on the control diet and other treatments (P < 0.05). Moreover, usage of feed dietary supplementation with B. brevis FJAT-1501-BPA had positive effects on levels of enzymes and minerals in blood. The alkaline phosphatase, alanine aminotransferase, Fe and Mg concentrations for weaned piglets fed diet containing B. brevis FJAT-1501-BPA fermentation were significantly higher than for those on the control diet (P < 0.05). Furthermore, concentration of IgG in serum was higher in weaned

7. Photocopy of Elevations drawing (from the BPA Engineering Vault, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Photocopy of Elevations drawing (from the BPA Engineering Vault, Drawing C13-J2-342-D1, Sheet 3, 13 March 1939) - Bonneville Power Administration South Bank Substation, I-84, South of Bonneville Dam Powerhouse, Bonneville, Multnomah County, OR

Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval.

PubMed

Monti Hughes, Andrea; Pozzi, Emiliano C C; Heber, Elisa M; Thorp, Silvia; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Molinari, Ana J; Garabalino, Marcela A; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2011-11-01

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10+BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10+BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrea Monti Hughes; Emiliano C.C. Pozzi; Elisa M. Heber

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT);more » (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.« less

9. Photocopy of Reinforced Concrete Details drawing (from the BPA ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Photocopy of Reinforced Concrete Details drawing (from the BPA Engineering Vault, Drawing C13-J2-342-D1, Sheet 6, 13 March 1939) - Bonneville Power Administration South Bank Substation, I-84, South of Bonneville Dam Powerhouse, Bonneville, Multnomah County, OR

Adverse effects of bisphenol A (BPA) on the dopamine system in two distinct cell models and corpus striatum of the Sprague-Dawley rat.

PubMed

Nowicki, Brittney A; Hamada, Matt A; Robinson, Gina Y; Jones, Douglas C

2016-01-01

The aim of this study was to examine the effects of bisphenol A (BPA) on the brain dopamine (DA) system utilizing both in vitro models (GH3 cells, a rat pituitary cell line, and SH-SY5Y cells, a human neuroblastoma cell line) and an animal model such as Sprague-Dawley (SD) rats. First, cellular DA uptake was measured 2 or 8 h following BPA exposure (0.1-400 μM) in SH-SY5Y cells, where a significant increase in DA uptake was noted. BPA exerted no marked effect on dopamine active transporter levels in GH3 cells exposed for 8 or 24 h. However, SH-SY5Y cells displayed an increase in dopamine transporter (DAT) levels following 24 h of exposure to BPA. In contrast to DAT levels, BPA exposure produced no marked effect on DA D1 receptor levels in SH-SY5Y cells, yet a significant decrease in GH3 cells following both 8- and 24-h exposure periods was noted, suggesting that BPA exerts differential effects dependent upon cell type. BPA produced no significant effects on prolactin levels at 2 h, but a marked fall occurred at 24 h of exposure in GH3 cells. Finally, to examine the influence of dietary developmental exposure to BPA on brain DA levels in F1 offspring, SD rats were exposed to BPA (0.5-20 mg/kg) through maternal transfer and/or diet and striatal DA levels were measured on postnatal day (PND) 60 using high-performance liquid chromatography (HPLC). Data demonstrated that chronic exposure to BPA did not significantly alter striatal DA levels in the SD rat.

"Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

2011-04-01

In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

“Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ana J. Molinari; Emiliano C. C. Pozzi; Andrea Monti Hughes

In the present study we evaluated the therapeutic effect and/or potential radiotoxicity of the novel “Tandem” Boron Neutron Capture Therapy (T-BNCT) for the treatment of oral cancer in the hamster cheek pouch model at RA-3 Nuclear Reactor. Two groups of animals were treated with “Tandem BNCT”, i.e. BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (T-24h-BNCT) or 48 h (T-48h-BNCT) later. A total tumor dose-matched single application of BNCT mediated by BPA and GB-10 administered jointly [(BPA + GB-10)-BNCT] was administered to an additional group of animals. At 28 days post-treatment, T-24h-BNCTmore » and T-48h-BNCT induced, respectively, overall tumor control (OTC) of 95% and 91%, with no statistically significant differences between protocols. Tumor response for the single application of (BPA + GB-10)-BNCT was 75%, significantly lower than for T-BNCT. The T-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47% and 60% of the animals respectively. No normal tissue radiotoxicity was associated to tumor control for any of the protocols. “Tandem” BNCT enhances tumor control in oral cancer and reduces or, at worst, does not increase, mucositis in dose-limiting precancerous tissue.« less

Vascular parameters continue to decrease post-exposure with simultaneous, but not individual exposure to BPA and hypoxia in zebrafish larvae.

PubMed

Cypher, Alysha D; Fetterman, Bryce; Bagatto, Brian

2018-04-01

How fish respond to hypoxia, a common stressor, can be altered by simultaneous exposure to pollutants like bisphenol A (BPA), a plasticizer. BPA is cardiotoxic and interferes with the hypoxia inducible factor pathway (HIF-1α), therefore disrupting the hypoxic response. Co-exposure to hypoxia and BPA also causes severe bradycardia and reduced cardiac output in zebrafish larvae. The purpose of this work was to determine how the cardiovascular effects of co-exposure vary with BPA concentration and persist beyond exposure. Zebrafish embryos were exposed to 0, 0.01, 0.1, 1, and 100 μg/L of BPA during normoxia (>6.0 mg/L O 2 ) and hypoxia (2.0 ± 0.5 mg/L O 2 ) between 1 h post fertilization (hpf) and late hatching (72-96 hpf). Heart rate, cardiac output, and red blood cell (RBC) velocity were determined through video microscopy and digital motion analysis at late hatching and 10 days post fertilization (dpf), several days post exposure. In comparison to the hypoxic control, RBC velocity was 25% lower with 0.01 μg/L BPA and hypoxia at late hatching. At 10 dpf, the difference in RBC velocity between these treatments doubled, despite several days of recovery. This coincided with a 24% thinner outer diameter for caudal vein but no effect on cardiac or developmental parameters. Statistical interactions between BPA and oxygen concentration were found for arterial RBC velocity at both ages. Because the co-occurrence of both stressors is extremely common, it would be beneficial to understand how BPA and hypoxia interact to affect cardiovascular function during and after exposure. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

PubMed Central

Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

2014-01-01

Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns

Comparing dietary and non-dietary source contribution of BPA and DEHP to prenatal exposure: A Catalonia (Spain) case study.

PubMed

Martínez, M A; Rovira, J; Prasad Sharma, R; Nadal, M; Schuhmacher, M; Kumar, V

2018-05-30

Bisphenol A (BPA) and Di-(2-ethylhexyl) phthalate (DEHP) are two wide spread chemicals classified as endocrine disruptors (ED). The present study aims to estimate the non-dietary (dermal, non-dietary ingestion and inhalation) exposure to BPA and DEHP for a pregnant women cohort. In addition, to assess the prenatal exposure for the fetus, a physiologically based pharmacokinetic (PBPK) model was used. It was adapted for pregnancy in order to assess the internal dosimetry levels of EDs (BPA and DEHP) in the fetus. Estimates of exposure to BPA and DEHP from all pathways along with their relative importance were provided in order to establish which proportion of the total exposure came from diet and which came from non-dietary exposures. In this study, the different oral dosing scenarios (dietary and non-dietary) were considered keeping inhalation as a continuous exposure case. Total non-dietary mean values were 0.002 µg/kg bw /day (0.000; 0.004 µg/kg bw /day for 5th and 95th percentile, respectively) for BPA and 0.597 µg/kg bw /day (0.116 µg/kg bw /day and 1.506 µg/kg bw /day for 5th and 95th percentile, respectively) for DEHP. Indoor environments and especially dust ingestion were the main non-dietary contributors to the total exposure of BPA and DEHP with 60% and 81%. However, as expected, diet showed the higher contribution to total exposure with > 99.9% for BPA and 63% for DEHP. Although diet was considered the primary source of exposure to BPA and phthalates, it must be taken into account that with non-dietary sources the first-pass metabolism is lacking, so these may be of equal or even higher toxicological relevance than dietary sources. The present study is in the framework of "Health and environmental-wide associations based on large population surveys" (HEALS) project (FP7-603946). Copyright © 2018 Elsevier Inc. All rights reserved.

Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

PubMed

Perona, M; Rodríguez, C; Carpano, M; Thomasz, L; Nievas, S; Olivera, M; Thorp, S; Curotto, P; Pozzi, E; Kahl, S; Pisarev, M; Juvenal, G; Dagrosa, A

2013-08-01

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹⁰BPA (10 μg ¹⁰B ml⁻¹) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ¹⁰BOPP (10 μg ¹⁰B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹⁰ n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

Chronic High Dose Intraperitoneal Bisphenol A (BPA) Induces Substantial Histological and Gene Expression Alterations in Rat Penile Tissue Without Impairing Erectile Function

PubMed Central

Kovanecz, Istvan; Gelfand, Robert; Masouminia, Maryam; Gharib, Sahir; Segura, Denesse; Vernet, Dolores; Rajfer, Jacob; Li, De-Kun; Liao, Chun Yang; Kannan, Kurunthachalam; Gonzalez-Cadavid, Nestor F.

2014-01-01

Introduction Bisphenol A (BPA), released from plastics and dental sealants, is a suspected endocrine disruptor and reproductive toxicant. In occupationally exposed workers, BPA has been associated with erectile dysfunction (ED). Aims To determine whether long-term exposure to high doses of BPA in the rat affects serum levels of testosterone (T) and estradiol (E2), and induces corporal histopathology and resultant ED. Methods Young rats were injected intraperitoneal (IP) injection daily with BPA at 25 mg/kg/day or vehicle (n = 8/group). Erectile function was measured at 3 months by cavernosometry and electrical field stimulation (EFS). BPA was assayed in serum, urine, and penile tissue, and serum T and E2 were determined. Quantitative Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling, Oil Red O, immunohistochemistry for calponin, α-smooth muscle actin, and Oct 4 were applied to penile tissue sections. Protein markers were assessed by Western blots and 2–D minigels, and RNA by DNA microarrays. Main Outcome Measures Erectile function, histological, and biochemical markers in corporal tissue. Results In the BPA-treated rats, total and free BPA levels were increased in the serum, urine, and penile tissue while serum T and E2 levels were reduced. In addition, the corpora cavernosa demonstrated a reduction in smooth muscle (SM) content, SM/collagen ratio, together with an increase in myofibroblasts, fat deposits, and apoptosis, but no significant change in collagen content or stem cells (nuclear/perinuclear Oct 4). In the penile shaft, BPA induced a downregulation of Nanog (stem cells), neuronal nitric oxide synthase (nitrergic terminals), and vascular endothelial growth factor (angiogenesis), with genes related to SM tone and cytoskeleton upregulated 5- to 50-fold, accompanied by changes in the multiple protein profile. However, both cavernosometry and EFS were unaltered by BPA. Conclusions While rats treated chronically with a high IP

Effects of perinatal bisphenol A exposure on the volume of sexually-dimorphic nuclei of juvenile rats: A CLARITY-BPA consortium study.

PubMed

Arambula, Sheryl E; Fuchs, Joelle; Cao, Jinyan; Patisaul, Heather B

2017-12-01

Bisphenol A (BPA) is a high volume endocrine disrupting chemical found in a wide variety of products including plastics and epoxy resins. Human exposure is nearly ubiquitous, and higher in children than adults. Because BPA has been reported to interfere with sex steroid hormone signaling, there is concern that developmental exposure, even at levels below the current FDA No Observed Adverse Effect Level (NOAEL) of 5mg/kg body weight (bw)/day, can disrupt brain sexual differentiation. The current studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program and tested the hypothesis that perinatal BPA exposure would induce morphological changes in hormone sensitive, sexually dimorphic brain regions. Sprague-Dawley rats were randomly assigned to 5 groups: BPA (2.5, 25, or 2500μg/kgbw/day), a reference estrogen (0.5μg ethinylestradiol (EE 2 )/kgbw/day), or vehicle. Exposure occurred by gavage to the dam from gestational day 6 until parturition, and then to the offspring from birth through weaning. Unbiased stereology was used to quantify the volume of the sexually dimorphic nucleus (SDN), the anteroventral periventricular nucleus (AVPV), the posterodorsal portion of the medial amygdala (MePD), and the locus coeruleus (LC) at postnatal day 28. No appreciable effects of BPA were observed on the volume of the SDN or LC. However, AVPV volume was enlarged in both sexes, even at levels below the FDA NOAEL. Collectively, these data suggest the developing brain is vulnerable to endocrine disruption by BPA at exposure levels below previous estimates by regulatory agencies. Copyright © 2017 Elsevier B.V. All rights reserved.

Transformation of Flame Retardant Tetrabromobisphenol A by Aqueous Chlorine and the Effect of Humic Acid.

PubMed

Gao, Yuan; Pang, Su-Yan; Jiang, Jin; Ma, Jun; Zhou, Yang; Li, Juan; Wang, Li-Hong; Lu, Xue-Ting; Yuan, Li-Peng

2016-09-06

In this work, it was found that the most widely used brominated flame retardant tetrabromobisphenol A (TBrBPA) could be transformed by free chlorine over a wide pH range from 5 to 10 with apparent second-order rate constants from 138 to 3210 M(-1)·s(-1). A total of eight products, including one quinone-like compound (i.e., 2,6-dibromoquinone), two dimers, and several simple halogenated phenols (e.g., 4-(2-hydroxyisopropyl)-2,6-dibromophenol, 2,6-dibromohydroquinone, and 2,4,6-tribromophenol), were detected by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) using a novel precursor ion scan (PIS) approach. A tentative reaction pathway was proposed: chlorine initially oxidized TBrBPA leading to the formation of a phenoxy radical, and then this primary radical and its secondary intermediates (e.g., 2,6-dibromo-4-isopropylphenol carbocation) formed via beta-scission subsequently underwent substitution, dimerization, and oxidation reactions. Humic acid (HA) considerably inhibited the degradation rates of TBrBPA by chlorine even accounting for oxidant consumption. A similar inhibitory effect of HA was also observed in permanganate and ferrate oxidation. This inhibitory effect was possibly attributed to the fact that HA competitively reacted with the phenoxy radical of TBrBPA and reversed it back to parent TBrBPA. This study confirms that chlorine can transform phenolic compounds (e.g., TBrBPA) via electron transfer rather than the well-documented electrophilic substitution, which also have implications on the formation pathway of halo-benzoquinones during chlorine disinfection. These findings can improve the understanding of chlorine chemistry in water and wastewater treatment.

THE ESTROGENIC ENDOCRINE DISRUPTING CHEMICAL BISPHENOL A (BPA) AND OBESITY

PubMed Central

vom Saal, Frederick S.; Nagel, Susan C.; Coe, Benjamin L.; Angle, Brittany M.; Taylor, Julia A.

2012-01-01

There is increasing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent increase in adult obesity and other components of metabolic syndrome. In particular, there is evidence that epigenetic changes associated with the use of manmade chemicals may interact with other factors that influence fetal and postnatal growth in contributing to the current obesity epidemic. The focus of this review is on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA), on adipocytes and their function, and the ultimate impact on adult obesity; BPA exposure also results in impaired reproductive capacity. We discuss the interaction of EDCs with other factors that impact growth during fetal and neonatal life, such as placental blood flow and nutrient transport to fetuses, and how these influence fetal growth and abnormalities in homeostatic control systems required to maintain normal body weight throughout life. PMID:22249005

Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio).

PubMed

Molina, Ana; Abril, Nieves; Morales-Prieto, Noelia; Monterde, José; Ayala, Nahúm; Lora, Antonio; Moyano, Rosario

2018-07-30

Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a "substance of very high concern" because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

Low-concentration exposure to BPA, BPF and BPAF induces oxidative DNA bases lesions in human peripheral blood mononuclear cells.

PubMed

Mokra, Katarzyna; Woźniak, Katarzyna; Bukowska, Bożena; Sicińska, Paulina; Michałowicz, Jaromir

2018-06-01

Because bisphenol A (BPA) and some of its analogs have been supposed to influence development of cancer, we have assessed the effect of BPA, bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) on DNA bases oxidation, which is a key process in cancer initiation. The analysis was conducted on human peripheral blood mononuclear cells (PBMCs), which are very useful model to assess genotoxic potential of various toxicants in different cell types. In order to determine oxidative damage to DNA pyrimidines and purines, alkaline version of the comet assay with DNA glycosylases, i.e. endonuclease III (Nth) and human 8-oxoguanine DNA glycosylase (hOGG1) was used. PBMCs were exposed to BPA or its analogs in the concentrations of 0.01, 0.1 and 1 μg/mL for 4 h and 0.001, 0.01 and 0.1 μg/mL for 48 h. We have observed that BPA, BPS, BPF and particularly BPAF caused oxidative damage to DNA pyrimidines and more strongly to purines in human PBMCs. The results have also shown that BPS, which is the most commonly used as a substitute for BPA in the manufacture induced definitely the smallest oxidative DNA bases lesions in PBMCs. Moreover, we have noticed that BPA, BPF and BPAF caused DNA damage at very low concentration of 1 ng/mL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acid loading test (pH)

MedlinePlus

... medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the kidneys to send ...

Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

PubMed

Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

2015-01-01

Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA. Copyright © 2015 Elsevier Inc. All rights reserved.

Estrogenic Effects of Several BPA Analogs in the Developing Zebrafish Brain

PubMed Central

Cano-Nicolau, Joel; Vaillant, Colette; Pellegrini, Elisabeth; Charlier, Thierry D.; Kah, Olivier; Coumailleau, Pascal

2016-01-01

Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA). The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4- or 7-day post-fertilization (dpf) zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B), expressed in the brain, using three different in situ/in vivo strategies: (1) Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols; (2) Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus); and (3) Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay) at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF, or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα). Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP) did not show estrogenic activity in our model. PMID:27047331

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

PubMed Central

Nanjappa, Manjunatha K.; Simon, Liz; Akingbemi, Benson T.

2012-01-01

ABSTRACT The presence of bisphenol A (BPA) in consumer products has raised concerns about potential adverse effects on reproductive health. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone, which supports the male phenotype. The present report describes the effects of developmental exposure of male rats to BPA by gavage of pregnant and lactating Long-Evans dams at 2.5 and 25 μg/kg body weight from Gestational Day 12 to Day 21 postpartum. This exposure paradigm stimulated Leydig cell division in the prepubertal period and increased Leydig cell numbers in the testes of adult male rats at 90 days. Observations from in vitro experiments confirmed that BPA acts directly as a mitogen in Leydig cells. However, BPA-induced proliferative activity in vivo is possibly mediated by several factors, such as 1) protein kinases (e.g., mitogen-activated protein kinases or MAPK), 2) growth factor receptors (e.g., insulin-like growth factor 1 receptor-beta and epidermal growth factor receptors), and 3) the Sertoli cell-secreted anti-Mullerian hormone (also called Mullerian inhibiting substance). On the other hand, BPA suppressed protein expression of the luteinizing hormone receptor (LHCGR) and the 17beta-hydroxysteroid dehydrogenase enzyme (HSD17B3), thereby decreasing androgen secretion by Leydig cells. We interpret these findings to mean that the likely impact of deficits in androgen secretion on serum androgen levels following developmental exposure to BPA is alleviated by increased Leydig cell numbers. Nevertheless, the present results reinforce the view that BPA causes biological effects at environmentally relevant exposure levels and its presence in consumer products potentially has implication for public health. PMID:22302688

Use of Immunohistochemistry to Demonstrate In Vivo Expression of the Burkholderia mallei Virulence Factor BpaB During Experimental Glanders.

PubMed

Zimmerman, Shawn M; Long, Mackenzie E; Dyke, Jeremy S; Jelesijevic, Tomislav P; Michel, Frank; Lafontaine, Eric R; Hogan, Robert J

2018-03-01

Burkholderia mallei causes the highly contagious and debilitating zoonosis glanders, which infects via inhalation or percutaneous inoculation and often culminates in life-threatening pneumonia and sepsis. In humans, glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. No vaccine exists to protect against B. mallei, and there is concern regarding its use as a bioweapon. The authors previously identified the protein BpaB as a potential target for devising therapies due to its role in adherence to host cells and the formation of biofilms in vitro and its contribution to pathogenicity in a mouse model of glanders. In the present study, the authors developed an immunostaining approach to probe tissues of experimentally infected animals and demonstrated that BpaB is produced exclusively in vivo by wild-type B. mallei in target organs from mice and marmosets. They detected the expression of BpaB by B. mallei both extracellularly and within macrophages, neutrophils, and epithelial cells in respiratory tissues (7/10 marmoset; 2/2 mouse). The authors also noted the intracellular expression of BpaB by B. mallei in macrophages in the regional lymph nodes of mice (2/2 tissues) and MALT of marmosets (4/5 tissues). It is interesting that B. mallei bacteria infecting distal organs did not express BpaB (2/2 mice; 3/3 marmosets), suggesting that the protein is not necessary for bacterial fitness in these anatomic locations. These findings underscore the value of BpaB as a target for developing medical countermeasures and provide insight into its role in pathogenesis.

Behavioural effect of low-dose BPA on male zebrafish: Tuning of male mating competition and female mating preference during courtship process.

PubMed

Li, Xiang; Guo, Jia-Yu; Li, Xu; Zhou, Hai-Jun; Zhang, Shu-Hui; Liu, Xiao-Dong; Chen, Dong-Yan; Fang, Yong-Chun; Feng, Xi-Zeng

2017-02-01

The ubiquity of environmental pollution by endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) is progressively considered as a major threat to aquatic ecosystems worldwide. Numerous toxicological studies have proved that BPA are hazardous to aquatic environment, along with alterations in the development and physiology of aquatic vertebrates. However, generally, there is a paucity in knowledge of behavioural and physiological effects of BPA with low concentration, for example, 0.22 nM (50 ng/L) and 2.2 nM (500 ng/L). Here we show that treatment of adult male zebrafish (Danio rerio) with 7 weeks low-dose (0.22 nM-2.2 nM) BPA, resulted in alteration in histological structure of testis tissue and abnormality in expression levels of genes involved in testicular steroidogenesis. Furthermore, low-dose BPA treatment decreased the male locomotion during courtship; and was associated with less courtship behaviours to female but more aggressive behaviours to mating competitor. Interestingly, during the courtship test, we observed that female preferred control male to male under low-dose BPA exposure. Subsequently, we found that the ability of female to chose optimal mating male through socially mutual interaction and dynamics of male zebrafish, which was based on visual discrimination. In sum, our results shed light on the potential behavioural and physiological effect of low-dose BPA exposure on courtship behaviours of zebrafish, which could exert profound consequences on natural zebrafish populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the sea urchin embryo.

PubMed

Bošnjak, Ivana; Borra, Marco; Iamunno, Franco; Benvenuto, Giovanna; Ujević, Ivana; Bušelić, Ivana; Roje-Busatto, Romana; Mladineo, Ivona

2014-11-01

Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted in global distribution of BPA in the environment. These high concentrations cause numerous negative effects to the aquatic biota, among which the most known is the induction of endocrine disruption. The focus of this research was to determine the effects of two experimentally determined concentrations of BPA (100nM and 4μM) on cellular detoxification mechanisms during the embryonic development (2-cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the potential involvement of multidrug efflux transport in the BPA intercellular efflux. The results of transport assay, measurements of the intracellular BPA and gene expression surveys, for the first time indicate the importance of P-glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA, validated by the immunohistochemistry (IHC) and the transmission electron microscopy (TEM), induced the aberrant karyokinesis, and consequently, the impairment of embryo development through the first cell division and retardation. Copyright © 2014 Elsevier B.V. All rights reserved.

CLARITY-BPA: Effects of chronic Bisphenol A exposure on the immune system: Part 1 - Quantification of the relative number and proportion of leukocyte populations in the spleen and thymus.

PubMed

Li, Jinpeng; Bach, Anthony; Crawford, Robert B; Phadnis-Moghe, Ashwini S; Chen, Weimin; D'Ingillo, Shawna; Kovalova, Natalia; Suarez-Martinez, Jose E; Zhou, Jiajun; Kaplan, Barbara L F; Kaminski, Norbert E

2018-03-01

Bisphenol A (BPA) is extensively used in manufacturing of a broad range of consumer products worldwide. Due to its widespread use, human exposure to BPA is virtually ubiquitous. Broad human exposure coupled with a large scientific literature describing estrogenic activity of BPA in animals has raised public health concerns. To comprehensively evaluate the health effects of BPA exposure, a chronic toxicity study using a wide-range of BPA doses (2.5-25000 μg/kg bw/day) was conducted jointly by the NTP, thirteen NIEHS-supported grantees, and the FDA, which is called the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, the objective of the current study was to evaluate the effects of chronic BPA exposure in Sprague-Dawley rats on the relative number and proportion of defined leukocyte populations in the spleen and the thymus. Toward this end, lymphoid tissues from a total of 641 rats were assayed after being continuously dosed with BPA or controls for up to one year. To comprehensively evaluate the effects of BPA on leukocyte compositions, extensive endpoints that cover major populations of leukocytes were assessed, including B cells, T cells, NK cells, granulocytes, monocytes, macrophages and dendritic cells. In total, of the 530 measurements in BPA-treated rats, 10 measurements were statistically different from vehicle controls and were mainly associated with either the macrophage or dendritic cell populations. Most, if not all, of these alterations were found to be transient with no persistent trend over the one-year time period. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and not dose-dependent. Due to the aforementioned, it is unlikely that the observed BPA-mediated changes alone would adversely affect immune competence. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR- Sprague-Dawley Rat: A CLARITY-BPA Study

PubMed Central

Gear, Robin; Kendziorski, Jessica A.; Belcher, Scott M.

2017-01-01

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the “Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 μg/kg/day, 0.05 or 0.5 μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90. PMID:28499613

Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR-Sprague-Dawley rat: A CLARITY-BPA study.

PubMed

Gear, Robin; Kendziorski, Jessica A; Belcher, Scott M

2017-06-05

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the "Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000μg/kg/day, 0.05 or 0.5μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Bisphenol-A (BPA) on insulin signal transduction and GLUT4 translocation in gastrocnemius muscle of adult male albino rat.

PubMed

Mullainadhan, Vigneswari; Viswanathan, Mangala Priya; Karundevi, Balasubramanian

2017-09-01

Environmental estrogens bind to estrogen receptors, mimic estrogenic actions, and have adverse effects on human health like Bisphenol - A (BPA) which is used as a monomer in the production of polycarbonate plastics (PC) and epoxy resins which are used in variety of canned foods. Skeletal muscle plays an essential role in maintaining systemic glucose metabolism. In the present study, we investigated the possible effects of BPA on insulin signalling molecules and GLUT4 translocation in the gastrocnemius muscle of adult male rat. Rats were divided into four groups - Group I: Control (vehicle-corn oil treated), Group II, III and IV were administered with BPA (10, 100 and 400mg/kg b.wt/day, respectively) through oral gavage. Fasting blood glucose level of BPA treated groups showed a significant increase, oral glucose tolerance and insulin tolerance were also impaired in these animals. BPA significantly decreased the protein levels of insulin signalling molecules like IR, IRS-1, Akt, AS160 and its phosphorylated forms and blunts GLUT4 translocation by altering the levels of v- and t- SNARE proteins that assist the translocation process, thereby decreasing glucose uptake and oxidation in the gastrocnemius muscle. These results suggest that BPA has detrimental effects on insulin signalling molecules and GLUT4 translocation in the gastrocnemius muscle and thus impairs glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity.

PubMed

Vom Saal, Frederick S; Nagel, Susan C; Coe, Benjamin L; Angle, Brittany M; Taylor, Julia A

2012-05-06

There is increasing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent increase in adult obesity and other components of metabolic syndrome. In particular, there is evidence that epigenetic changes associated with the use of manmade chemicals may interact with other factors that influence fetal and postnatal growth in contributing to the current obesity epidemic. The focus of this review is on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA), on adipocytes and their function, and the ultimate impact on adult obesity; BPA exposure also results in impaired reproductive capacity. We discuss the interaction of EDCs with other factors that impact growth during fetal and neonatal life, such as placental blood flow and nutrient transport to fetuses, and how these influence fetal growth and abnormalities in homeostatic control systems required to maintain normal body weight throughout life. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice.

PubMed

Rubin, Beverly S; Paranjpe, Maneesha; DaFonte, Tracey; Schaeberle, Cheryl; Soto, Ana M; Obin, Martin; Greenberg, Andrew S

2017-03-01

Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and adiposity, and to assess potential sex differences in this response. Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition. The effects were dose specific and sex specific and were influenced by the precise window of BPA exposure. The addition of peripubertal BPA exposure following the initial perinatal exposure exacerbated adverse effects in the females but appeared to reduce differences in body weight and body composition between control and BPA exposed males. Some effects of BPA on body weight and body composition showed a non-linear dose response. Copyright © 2016. Published by Elsevier Inc.

Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice

PubMed Central

Rubin, Beverly S.; Paranjpe, Maneesha; DaFonte, Tracey; Schaeberle, Cheryl; Soto, Ana M.; Obin, Martin; Greenberg, Andrew S.

2017-01-01

Body weight (BW) and body composition were examined in CD-1 mice exposed perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure window(s) that increased BW and adiposity, and to assess potential sex differences in this response. Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition. The effects were dose specific and sex specific and were influenced by the precise window of BPA exposure. The addition of peripubertal BPA exposure following the initial perinatal exposure exacerbated adverse effects in the females but appeared to reduce differences in body weight and body composition between control and BPA exposed males. Some effects of BPA on body weight and body composition showed a non-linear dose response. PMID:27496714

Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

PubMed Central

MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

2014-01-01

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

Effects of temperature on adsorption and oxidative degradation of bisphenol A in an acid-treated iron-amended granular activated carbon

EPA Science Inventory

The present study suggests a combined adsorption and Fenton oxidation using an acid treated Fe-amended granular activated carbon (Fe-GAC) for effective removal of bisphenol A in water. When the Fe-GAC adsorbs and is saturated with BPA in water, Fenton oxidation of BPA occurs in ...

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting under...

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting under...

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PubMed

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-10-01

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Elevated Metabolites of Steroidogenesis and Amino Acid Metabolism in Preadolescent Female Children With High Urinary Bisphenol A Levels: A High-Resolution Metabolomics Study.

PubMed

Khan, Adnan; Park, Hyesook; Lee, Hye Ah; Park, Bohyun; Gwak, Hye Sun; Lee, Hye-Ra; Jee, Sun Ha; Park, Youngja H

2017-12-01

Health risks associated with bisphenol A (BPA) exposure are controversially highlighted by numerous studies. High-resolution metabolomics (HRM) can confirm these proposed associations and may provide a mechanistic insight into the connections between BPA exposure and metabolic perturbations. This study was aimed to identify the changes in metabolomics profile due to BPA exposure in urine and serum samples collected from female and male children (n = 18) aged 7-9. Urine was measured for BPA concentration, and the children were subsequently classified into high and low BPA groups. HRM, coupled with Liquid chromatography-mass spectrometry/MS, followed by multivariate statistical analysis using MetaboAnalyst 3.0, were performed on urine to discriminate metabolic profiles between high and low BPA children as well as males and females, followed by further validation of our findings in serum samples obtained from same population. Metabolic pathway analysis showed that biosynthesis of steroid hormones and 7 other pathways-amino acid and nucleotide biosynthesis, phenylalanine metabolism, tryptophan metabolism, tyrosine metabolism, lysine degradation, pyruvate metabolism, and arginine biosynthesis-were affected in high BPA children. Elevated levels of metabolites associated with these pathways in urine and serum were mainly observed in female children, while these changes were negligible in male children. Our results suggest that the steroidogenesis pathway and amino acid metabolism are the main targets of perturbation by BPA in preadolescent girls. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bioaccumulation and elimination of bisphenol a (BPA) in the alga Chlorella pyrenoidosa and the potential for trophic transfer to the rotifer Brachionus calyciflorus.

PubMed

Guo, Ruixin; Du, Yingxiang; Zheng, Fengzhu; Wang, Jing; Wang, Zhiliang; Ji, Rong; Chen, Jianqiu

2017-08-01

In this study, we investigated the bioaccumulation and elimination of 14 C-labeled BPA by the green alga Chlorella pyrenoidosa and the subsequent transfer of 14 C-BPA residues from the contaminated alga to the rotifer Brachionus calyciflorus. After 10 days of BPA exposure, the algal cells accumulated 15% of the initial radioactivity from the medium, with 71% of the accumulated radioactivity occurring in the form of non-extractable bound residues. An approximate steady state of the accumulation of the 14 C-BPA residues in the algae was reached after about 4 days of exposure. The bioconcentration factor of total radioactivity in the algae was 106 mL (g dry weight) -1  at steady state. During the elimination phase, only the extractable residues were released from the algae into the water whereas the bound residues, following their ingestion by the rotifers, were converted to extractable forms and then also released. Furthermore, our results demonstrated the biomagnification of BPA-related residues in the food chain between algae and rotifers. The trophic transfer of these BPA-derived residues from the algae to rotifers and thus the environmental hazard may posed by this pathway, because of subsequent effects on the food chain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring.

PubMed

Dunder, Linda; Halin Lejonklou, Margareta; Lind, Lars; Risérus, Ulf; Lind, P Monica

2018-06-06

Bisphenol A (BPA) is an endocrine disruptor and also a suggested obesogen and metabolism-disrupting chemical. Accumulating data indicates that the fatty acid (FA) profile and their ratios in plasma and other metabolic tissues are associated with metabolic disorders. Stearoyl-CoA desaturase 1 (SCD-1) is a key regulator of lipid metabolism and its activity can be estimated by dividing the FA product by its precursor measured in blood or other tissues. The primary aim of this study was to investigate the effect of low-dose developmental BPA exposure on tissue-specific FA composition including estimated SCD-1 activity, studied in 5- and 52-week (wk)-old Fischer 344 (F344) rat offspring. Pregnant F344 rats were exposed to BPA via their drinking water corresponding to 0: [CTRL], 0.5: [BPA0.5], or 50 µg/kg BW/day: [BPA50], from gestational day 3.5 until postnatal day 22. BPA0.5 increased SCD-16 (estimated as the 16:1n-7/16:0 ratio) and SCD-18 (estimated as the 18:1n-9/18:0 ratio) indices in inguinal white adipose tissue triglycerides (iWAT-TG) and in plasma cholesterol esters (PL-CE), respectively, in 5-wk-old male offspring. In addition, BPA0.5 altered the FA composition in male offspring, e.g. by decreasing levels of the essential polyunsaturated FA linoleic acid (18:2n-6) in iWAT-and liver-TG. No differences were observed regarding the studied FAs in 52-wk-old offspring, although a slightly increased BW was observed in 52-wk-old female offspring. Low-dose developmental BPA exposure increased SCD-16 in iWAT-TG and SCD-18 in PL-CE of male offspring, which may reflect higher SCD-1 activity in these tissues. Altered desaturation activity and signs of altered FA composition are novel findings that may indicate insulin resistance in the rat offspring. These aforementioned results, together with the observed increased BW, adds to previously published data demonstrating that BPA can act as a metabolism disrupting chemical. Copyright © 2018 The Authors. Published by

Single, competitive, and dynamic adsorption on activated carbon of compounds used as plasticizers and herbicides.

PubMed

Abdel daiem, Mahmoud M; Rivera-Utrilla, José; Sánchez-Polo, Manuel; Ocampo-Pérez, Raúl

2015-12-15

The main aim of this study was to investigate the single, competitive, and dynamic adsorption of phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA), 2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2-methylphenoxyacetic acid (MCPA) on two activated carbons with different chemical natures and similar textural characteristics. The adsorption mechanism was also elucidated by analyzing the influence of solution pH and ionic strength. The activated carbons demonstrated high adsorption capacity to remove all micropollutants due to the presence of active sites on their surfaces, which increase dispersive interactions between the activated carbon graphene layers and the aromatic ring of pollutants. The adsorption capacity of the activated carbons increased in the order: DPA<BPAacid pH (pH<5) due to the establishment of attractive electrostatic interactions. In dynamic regime, the amount of pollutant adsorbed was much higher for PA, followed by DPA, and was approximately similar for BPA, 2,4-D, and MCPA. Finally, the amount of BPA and DPA adsorbed on activated carbon decreased by around 50% and 70% in the presence of DPA and BPA, respectively, indicating that both compounds are adsorbed on the same adsorption sites of the activated carbon. Copyright © 2015 Elsevier B.V. All rights reserved.

Urinary sexual steroids associated with bisphenol A (BPA) exposure in the early infant stage: Preliminary results from a Daishan birth cohort.

PubMed

Wang, Heng; Liu, Liangpo; Wang, Jianyue; Tong, Zhendong; Yan, Jianbo; Zhang, Tongjie; Qin, Ying; Jiang, Tingting; She, Jianwen; Shen, Heqing

2017-12-01

Many surveys have shown that older children are ubiquitously exposed to bisphenol A (BPA), and many laboratory studies have shown that BPA exposure has adverse effects related to estrogenic disruption, whereas the evidence in infants has not yet been observed. Women in early pregnancy were recruited by the Maternal and Child Health and Family Planning Service Center, Daishan, China, from March 2012 to December 2014. After delivery, urine samples were collected from the diapers of 59 infants (0 to 6months of age). Urinary BPA, estradiol (E 2 ), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and creatinine were analyzed. The partial correlation and multivariable linear regression were applied to assess the associations of BPA with E 2 , T, FSH, and LH for each of the development stages: at birth, 14days, 28days, 42days, 3months, and 6months. For both genders from birth to 6months, infants showed randomly changed urinary BPA but regularly changed hormones, i.e., the monotonic decreasing E 2 and T, the "U" shaping E 2 /T and upside down "U" shaping FSH and LH with extreme values at approximately the 14-day stage, respectively. However, the creatinine-adjusted FSH for all stages and E 2 from 6months were genders different. After adjustment for creatinine, gender, and infant body mass index, BPA was positively associated with E 2 both in male (for 14-, 28-, and 42-day stages) and female (for 14-, 28-, 42-day, and 3-month stages) infants; positively associated with E 2 /T ratio in both male (for 14- and 28-day stages) and female (for 14-day stage) infants; and positively associated with T in female (for 3-month stage) infants. To the best of our knowledge, this is the first time that associations of BPA with E 2 , E 2 /T, and T in infant urine were observed. The results suggested that the infants first demonstrate a surge of steroids after leaving the maternal uterus's steroidogenic environment (i.e., mini-puberty) and may be affected by

Tualang Honey Protects against BPA-Induced Morphological Abnormalities and Disruption of ERα, ERβ, and C3 mRNA and Protein Expressions in the Uterus of Rats

PubMed Central

Mohamad Zaid, Siti Sarah; Kassim, Normadiah M.; Othman, Shatrah

2015-01-01

Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can disrupt the normal functions of the reproductive system. The objective of the study is to investigate the potential protective effects of Tualang honey against BPA-induced uterine toxicity in pubertal rats. The rats were administered with BPA by oral gavage over a period of six weeks. Uterine toxicity in BPA-exposed rats was determined by the degree of the morphological abnormalities, increased lipid peroxidation, and dysregulated expression and distribution of ERα, ERβ, and C3 as compared to the control rats. Concurrent treatment of rats with BPA and Tualang honey significantly improved the uterine morphological abnormalities, reduced lipid peroxidation, and normalized ERα, ERβ, and C3 expressions and distribution. There were no abnormal changes observed in rats treated with Tualang honey alone, comparable with the control rats. In conclusion, Tualang honey has potential roles in protecting the uterus from BPA-induced toxicity, possibly accounted for by its phytochemical properties. PMID:26788107

Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study.

PubMed

Dere, Edward; Anderson, Linnea M; Huse, Susan M; Spade, Daniel J; McDonnell-Clark, Elizabeth; Madnick, Samantha J; Hall, Susan J; Camacho, Luísa; Lewis, Sherry M; Vanlandingham, Michelle M; Boekelheide, Kim

2018-05-15

Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA (2.5, 25, 250, 2500, 25,000, 250,000 μg/kg/d) or vehicle control. At PND 90, the testes and sperm were collected for evaluation. The testes were histologically evaluated for altered germ cell apoptosis, sperm production, and altered spermiation. RNA and DNA isolated from sperm were assessed for elicited changes in global mRNA transcript abundance and altered DNA methylation. Effects of BPA were observed in changes in body, testis and epididymis weights only at the highest administered dose of BPA of 250,000 μg/kg/d. Genome-wide transcriptomic and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA methylation levels. These data indicate that prolonged exposure starting in utero to BPA over a wide range of levels has little, if any, impact on the testes and sperm molecular profiles of 90 day old rats as assessed by the histopathologic, morphometric, and molecular endpoints evaluated. Copyright © 2018. Published by Elsevier Inc.

Temporal trends in bisphenol A exposure in the United States from 2003-2012 and factors associated with BPA exposure: Spot samples and urine dilution complicate data interpretation.

PubMed

LaKind, Judy S; Naiman, Daniel Q

2015-10-01

Nationally representative data on urinary levels of BPA and its metabolites in the United States from the 2003-2004 to 2011-2012 National Health and Nutrition Examination Surveys (NHANES) were used to estimate daily BPA intakes and examine temporal trends. Additionally, NHANES data on lifestyle/demographic/dietary factors previously reported to be associated with BPA exposures were examined to assess the resiliency of the reported associations (whether the association is maintained across the five surveys). Finally, various approaches for addressing issues with the use of BPA concentration data from spot urine samples were examined for their effect on trends and associations. Three approaches were assessed here: (i) use of generic literature-based 24-h urine excretion volumes, (ii) use of creatinine adjustments, and (iii) use of individual urine flow rate data from NHANES. Based on 2011-2012 NHANES urinary BPA data and assumptions described in this paper, the median daily intake for the overall population is approximately 25 ng/kg day; median intake estimates were approximately two to three orders of magnitude below current health-based guidance values. Estimates of daily BPA intake have decreased significantly compared to those from the 2003-2004 NHANES. Estimates of associations between lifestyle/demographic/dietary factors and BPA exposure revealed inconsistencies related to both NHANES survey year and the three approaches listed above; these results demonstrate the difficulties in interpreting urinary BPA data, despite efforts to account for urine dilution and translation of spot sample data to 24-h data. The results further underscore the importance of continued research on how to best utilize urinary measures of environmental chemicals in exposure research. Until a consensus is achieved regarding the best biomonitoring approaches for assessing exposures to short-lived chemicals using urine samples, research on factors associated with BPA exposures should

Synergistic effects of TiO2 and Cu2O in UV/TiO2/zeolite-based systems on photodegradation of bisphenol A.

PubMed

Kuo, Chao-Yin; Wu, Chung-Hsin; Lin, Han-Yu

2014-08-01

In this study, TiO2/zeolite (TZ)-based composite was utilized to degrade bisphenol A (BPA) under ultraviolet (UV) irradiation. The effects of the TiO2 and Cu2O doses in TZ and Cu2O/TiO2/zeolite (CTZ) on the rate of BPA removal were identified, respectively. The surface area of TZ declined as the TiO2 loading increased. The photodegradation rate (k) of BPA in the TZ and CTZ systems fitted pseudo-first-order kinetics. Under UV (365 nm) irradiation, the k values of TiO2 (20%)/zeolite (80%), TiO2 (40%)/zeolite (60%), TiO2 (60%)/zeolite (40%), and TiO2 (80%)/zeolite (20%) were 0.51, 0.55, 0.97, and 0.91 h-1, respectively. In the UV (365nm)/TiO2 (60%)/zeolite (40%) system, the k values of CTZ with 1%, 5%, 10%, 20%, and 30% Cu2O added were 1.50, 1.04, 1.15, 1.88, and 0.47h-1, respectively. The photocatalytic activity of TZ was enhanced by adding Cu2O. The optimal dosage of TiO2 in the TZ system was 60% and that of Cu20 in the CTZ system was 20%. p-Hydroxybenzaldehyde (p-HBA), p-hydroxyacetophenone (p-HAP), p-hydroxybenzoic acid (p-HBA acid) and hydroquinone (HQ) were intermediates ofBPA photodegradation in the UV/TZ system and the rates of degradation followed the order HQ > p - HBA acid > BPA > p - HAP > p - HBA.

The Future Impact of Wind on BPA Power System Ancillary Services

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarov, Yuri V.; Lu, Shuai; McManus, Bart

Wind power is growing in a very fast pace as an alternative generating resource. As the ratio of wind power over total system capacity increases, the impact of wind on various system aspects becomes significant. This paper presents a methodology to study the future impact of wind on BPA power system ancillary services including load following and regulation. Existing approaches for similar analysis include dispatch model simulation and standard deviation evaluation. The methodology proposed in this paper uses historical data and stochastic processes to simulate the load balancing processes in BPA power system. Then capacity, ramp rate and ramp durationmore » characteristics are extracted from the simulation results, and load following and regulation requirements are calculated accordingly. It mimics the actual power system operations therefore the results can be more realistic yet the approach is convenient to perform. Further, the ramp rate and ramp duration data obtained from the analysis can be used to evaluate generator response or maneuverability and energy requirement, respectively, additional to the capacity requirement.« less

Fabricating 3D porous PANI/TiO2-graphene hydrogel for the enhanced UV-light photocatalytic degradation of BPA

NASA Astrophysics Data System (ADS)

Chen, Fangyuan; An, Weijia; Li, Yao; Liang, Yinghua; Cui, Wenquan

2018-01-01

Polyaniline (PANI)/TiO2 composite graphene hydrogel was successfully prepared by chemical reduction method. TiO2 and PANI were uniformly dispersed in the three-dimensional network of graphene hydrogels. This rich network of macroscopic structures not only provides desirable conditions for synergistic adsorption and photocatalytic degradation of pollutants, but also improves the chemical stability of composites. Specifically, 80% PANI/TiO2-reduced graphene oxide hydrogel (rGH) can completely degrade BPA in 40 min, and BPA was almost completely mineralized into small molecules in 65 min. After five cycles of experiments, the degradation rate of PANI/TiO2-rGH for BPA was more than 90%. XPS analysis indicated that there is a strong interaction between PANI and TiO2. Hydrogen bonding between TiO2 and rGH was also demonstrated. Quenching experiments indicated •O2- and h+ are the main active species in the degradation of BPA by PANI/TiO2-rGH and •OH and h+ are the main active species by PANI/TiO2, suggesting that rGH and PANI acts as a transmitter for e- and h+, respectively.

Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity.

PubMed

Carchia, E; Porreca, I; Almeida, P J; D'Angelo, F; Cuomo, D; Ceccarelli, M; De Felice, M; Mallardo, M; Ambrosino, C

2015-10-29

Epidemiologic and experimental studies have associated changes of blood glucose homeostasis to Bisphenol A (BPA) exposure. We took a toxicogenomic approach to investigate the mechanisms of low-dose (1 × 10(-9 )M) BPA toxicity in ex vivo cultures of primary murine pancreatic islets and hepatocytes. Twenty-nine inhibited genes were identified in islets and none in exposed hepatocytes. Although their expression was slightly altered, their impaired cellular level, as a whole, resulted in specific phenotypic changes. Damage of mitochondrial function and metabolism, as predicted by bioinformatics analyses, was observed: BPA exposure led to a time-dependent decrease in mitochondrial membrane potential, to an increase of ROS cellular levels and, finally, to an induction of apoptosis, attributable to the bigger Bax/Bcl-2 ratio owing to activation of NF-κB pathway. Our data suggest a multifactorial mechanism for BPA toxicity in pancreatic islets with emphasis to mitochondria dysfunction and NF-κB activation. Finally, we assessed in vitro the viability of BPA-treated islets in stressing condition, as exposure to high glucose, evidencing a reduced ability of the exposed islets to respond to further damages. The result was confirmed in vivo evaluating the reduction of glycemia in hyperglycemic mice transplanted with control and BPA-treated pancreatic islets. The reported findings identify the pancreatic islet as the main target of BPA toxicity in impairing the glycemia. They suggest that the BPA exposure can weaken the response of the pancreatic islets to damages. The last observation could represent a broader concept whose consideration should lead to the development of experimental plans better reproducing the multiple exposure conditions.

Analytical determination of bisphenol A (BPA) and bisphenol analogues in paper products by GC-MS/MS.

PubMed

Jurek, A; Leitner, E

2017-07-01

Bisphenol A (BPA; 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol), a suspected endocrine disruptor with a weak estrogenic activity, is used in a variety of consumer products, including food-contact materials made of paper and cardboard products. Due to restrictions on the use of BPA because of its potential health risks, BPA is gradually being replaced by other bisphenols because no limitations exist for these substances. This study presents a method for the simultaneous analysis of BPA, bisphenol AF (BPAF), bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF) and bisphenol S (BPS) in paper and board products using gas chromatography-tandem mass spectrometry (GC-MS/MS). Paper samples were extracted by liquid extraction, as well as by Folch extraction, derivatised with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and the results compared. The developed method showed good linearity (R 2  > 0.9965) and precision, yielding relative standard deviations (RSDs) of less than 16.6% for reproducibility and 19.8% for repeatability. The limits of detection and limits of quantification for the different bisphenols ranged from 0.23 to 2.70 µg kg - 1 paper and from 0.78 to 9.10 µg kg - 1 paper, respectively. Analysis of different paper products (recycled, virgin fibre) showed that all the analysed bisphenols were present in the samples, except for BPAF and BPB. A calculation of the 'worst-case' scenario assuming a maximum potential migration of 100% of the analytes into food showed that the analysed products can be assumed to be safe regarding the migration of bisphenols.

Impact of low-dose chronic exposure to Bisphenol A (BPA) on adult male zebrafish adaption to the environmental complexity: Disturbing the color preference patterns and reliving the anxiety behavior.

PubMed

Li, Xiang; Sun, Ming-Zhu; Li, Xu; Zhang, Shu-Hui; Dai, Liang-Ti; Liu, Xing-Yu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2017-11-01

The extensive usage of xenobiotic endocrine disrupting chemicals (XEDCs), such as Bisphenol A (BPA), has created obvious threat to aquatic ecosystems worldwide. Although a comprehensive understanding of the adverse effect of BPA on behaviors and physiology have been proven, the potential impact of low-dose BPA on altering the basic ability of aquatic organism in adapting to the surrounded complex environment still remains elusive. In this research, we report that treatment of adult male zebrafish with chronic (7 weeks) low-dose (0.22 nM-2.2 nM) BPA, altered the ability in adapting the complex environment by disturbing the natural color preference patterns. In addition, chronic 50 ng/L (0.22 nM) BPA exposure alleviated the anxiety behavior of male zebrafish confronted with the novel environment by enhancing the preference towards light in the light/dark preference test. This phenotype was associated with less expression of serotonin (5-TH) in the hypothalamus and the down-regulation of tyrosine hydroxylase (TH) in brain tissues. As such, our results show that low-dose BPA remnant in surface waters altered zebrafish behavior that are known to have ecological and evolutionary consequences. Here we reported that the impact of chronic low-dose BPA exposure on the basic capability of zebrafish to adapt to the environmental complexity. Specifically, BPA at low concentration, under the environmental safety level and 3000-fold lower than the accepted human daily exposure, interfered with the ability to discriminate color and alleviate anxiety induced by the novel environment, which finally altered the capability of male zebrafish to adapt to the environmental complexity. These findings revealed the ecological effect of low-dose BPA and regular BPA concentration standard are not necessarily safe. The result also provided the consideration of retuning the hazard concentration level of BPA. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro impact of bisphenols BPA, BPF, BPAF and 17β-estradiol (E2) on human monocyte-derived dendritic cell generation, maturation and function.

PubMed

Švajger, Urban; Dolenc, Marija Sollner; Jeras, Matjaž

2016-05-01

Bisphenols (BPs) are widely spread pollutants that act as estrogen-like endocrine disruptors and are potentially affecting human health on a long run. We explored the effects of BPA, BPF and BPAF, on in vitro differentiation and maturation of MDDCs. Monocytes were treated with 17β-estradiol (E2) and each BP at the beginning of their differentiation into iMDDCs. We found that 10 and 50 μM of BPA and BPF, 10 and 30μM of BPAF and 10 and 50 nM of E2 did not affect cell viability. However, 50 μM of BPA and BPF, as well as 10 and 30 μM of BPAF, significantly decreased the endocytotic capacity of iMDDCs. Both, BPA (50 μM) and BPAF (30 μM) decreased the expression of CD1a and increased the amount of DC-SIGN molecules on iMDDCs. The E2 pre-treatment moderately decreased expression of CD80, CD86 and CD83 co-stimulatory molecules while increasing the numbers of HLA-DR on mMDDCs. Only BPAF significantly influenced the expression of CD80 and CD86 (both decreased), as well as CD83 and HLA-DR molecules (both increased) on mMDDCs. In addition, BPAF modulated DC maturation signaling pathways by lowering the phosphorylation of p65 NF-κB (nuclear factor-kappaB) and ERK (extracellular signal regulated kinase) 1/2 proteins. Consequently, the in vitro proliferation of allogeneic T cells, stimulated with differently pre-treated iMDDCs and mMDDCs, was significantly reduced only in case of BPAF. Copyright © 2016 Elsevier B.V. All rights reserved.

EVALUATION OF ORAL AND INTRAVENOUS ROUTE PHARMACOKINETICS, PLASMA PROTEIN BINDING AND UTERINE TISSUE DOSE METRICS OF BPA: A PHYSIOLOGICALLY BASED PHARMACOKINETIC APPROACH

EPA Science Inventory

Bisphenol A (BPA) is a weakly estrogenic monomer used in the production of polycarbonate plastics and epoxy resins, both of which are used in food contact applications. A physiologically based pharmacokinetic (PBPK) model of BPA pharmacokinetics in rats and humans was developed t...

EVALUATION OF ORAL AND INTRAVENOUS ROUTE PHARMACOKINETICS, PLASMA PROTEIN BINDING AND UTERINE TISSUE DOSE METRICS OF BPA: A PHYSIOLOGICALLY BASED PHARMACOKINETIC APPROACH

EPA Science Inventory

Bisphenol A (BPA) is a weakly estrogenic monomer used in the production of polycarbonate plastics and epoxy resins, both of which are used in food contact applications. A physiologically based pharmacokinetic (PBPK) model of BPA pharmacokinetics in rats and humans was developed ...

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor.

PubMed

Monti Hughes, Andrea; Longhino, Juan; Boggio, Esteban; Medina, Vanina A; Martinel Lamas, Diego J; Garabalino, Marcela A; Heber, Elisa M; Pozzi, Emiliano C C; Itoiz, María E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2017-11-01

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.

Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

PubMed

Roda, E; Nion, S; Bernocchi, G; Coccini, T

2014-10-02

Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

D. W. Nigg

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in themore » hamster cheek pouch model of oral cancer.« less

Bisphenol A (BPA) Exposure In Utero Leads to Immunoregulatory Cytokine Dysregulation in the Mouse Mammary Gland: A Potential Mechanism Programming Breast Cancer Risk.

PubMed

Fischer, Catha; Mamillapalli, Ramanaiah; Goetz, Laura G; Jorgenson, Elisa; Ilagan, Ysabel; Taylor, Hugh S

2016-08-01

Bisphenol-A (BPA) is a ubiquitous estrogen-like endocrine disrupting compound (EDC). BPA exposure in utero has been linked to breast cancer and abnormal mammary gland development in mice. The recent rise in incidence of human breast cancer and decreased age of first detection suggests a possible environmental etiology. We hypothesized that developmental programming of carcinogenesis may involve an aberrant immune response. Both innate and adaptive immunity play a role in tumor suppression through cytolytic CD8, NK, and Th1 T-cells. We hypothesized that BPA exposure in utero would lead to dysregulation of both innate and adaptive immunity in the mammary gland. CD1 mice were exposed to BPA in utero during gestation (days 9-21) via osmotic minipump. At 6 weeks, the female offspring were ovariectomized and estradiol was given at 8 weeks. RNA and protein were extracted from the posterior mammary glands, and the mRNA and protein levels were measured by PCR array, qRT-PCR, and western blot. In mouse mammary tissue, BPA exposure in utero significantly decreased the expression of members of the chemokine CXC family (Cxcl2, Cxcl4, Cxcl14, and Ccl20), interleukin 1 (Il1) gene family (Il1β and Il1rn), interleukin 2 gene family (Il7 receptor), and interferon gene family (interferon regulatory factor 9 (Irf9), as well as immune response gene 1 (Irg1). Additionally, BPA exposure in utero decreased Esr1 receptor gene expression and increased Esr2 receptor gene expression. In utero exposure of BPA resulted in significant changes to inflammatory modulators within mammary tissue. We suggest that dysregulation of inflammatory cytokines, both pro-inflammatory and anti-inflammatory, leads to a microenvironment that may promote disordered cell growth through inhibition of the immune response that targets cancer cells.

In situ H(+)-mediated formation of singlet oxygen from NaBiO3 for oxidative degradation of bisphenol A without light irradiation: Efficiency, kinetics, and mechanism.

PubMed

Ding, Yaobin; Xia, Xiangli; Ruan, Yufeng; Tang, Heqing

2015-12-01

Bisphenol A (BPA) is a ubiquitous environmental contaminant with endocrine disruption potential. This study explored the efficiency, kinetics, and mechanism of BPA removal from weakly acidic solutions by using NaBiO3 as a source of singlet oxygen. It was observed that the use of NaBiO3 (1gL(-1)) could eliminate almost all (more than 97%) of the added BPA (0.1mmolL(-1)) in solutions at pH 5.0 in 60min. The degradation of BPA followed pseudo-first-order kinetics over the pH range from 3 to 9, and the pseudo-first-order rate constant (k) was dependent on pH, NaBiO3 concentration and the coexisting compounds. As solution pH was decreased from 9 to 3 or NaBiO3 concentration was increased from 0.5 to 2gL(-1), the k value was increased logarithmically. Humic acid and Fe(3+) showed little effect on the BPA removal, but Mn(2+) exhibited exceptionally enhancing effect on the degradation of BPA. The involved reactive species were identified as singlet oxygen by using radical scavenger probes and ESR measurement, and the generated singlet oxygen was confirmed to be generated from the decomposition of NaBiO3 mediated by H(+) ions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous production of laccase and degradation of bisphenol A with Trametes versicolor cultivated on agricultural wastes.

PubMed

Zeng, Shengquan; Zhao, Jie; Xia, Liming

2017-08-01

Solid state fermentation with Trametes versicolor was carried out on agricultural wastes containing bisphenol A (BPA). It was found that BPA degradation was along with the occurrence of laccase production, and wheat bran and corn straw were identified as suitable mixed substrates for laccase production. In the process of BPA degradation with T. versicolor, laccase activity increased rapidly at the 6th-10th day after inoculation. Moreover, BPA can enhance the production of laccase. After 10 days of fermentation, degradation rate of BPA exceeded 90% without the usage of mediators ABTS and acetosyringone at pH 4.0-8.0. In addition, metal ions did not affect the BPA degradation with T. versicolor. In vitro, the optimum pH range of BPA degradation with laccase was in the acidic region with the optimal performance of pH 5.0. Metal ions Cu 2+ , Zn 2+ , and Co 2+ showed little effect on BPA degradation. However, Fe 3+ and Fe 2+ substantially inhibited the BPA degradation. Natural mediator acetosyringone showed optimum enhancement on BPA degradation. Greater than 90% of the estrogenic activity of BPA was removed by T. versicolor and its laccase. Compared to in vitro degradation with laccase, this study shows that the process of simultaneous laccase production and BPA degradation with T. versicolor was more advantageous since BPA can enhance the laccase production, mediators were unnecessary, degradation rate was not affected by metal ions, and the applicable pH range was broader. This study concludes that T. versicolor and laccase have great potential to treat industrial wastewater containing BPA.

Alteration in apoptotic rate of testicular cells and sperms following administration of Bisphenol A (BPA) in Wistar albino rats.

PubMed

Srivastava, Seema; Gupta, Priya

2018-05-21

The aim of the study was to evaluate the effect of Bisphenol A [BPA] widely used as a plasticizer in the formation of polycarbonate plastics and epoxy resins, exposure causing alteration in apoptosis rate, and protective effect of Vitamin E when supplemented with BPA orally. Adult male Wistar albino rats aged 3 months were randomly divided into seven groups: control (olive oil treated) BPA-treated (dose 5, 50,100 μg/100gmBW) and Vitamin E intervention group (dose 5, 50, 100 μg/100gmBW BPA+ Vitamin E dose 4 mg/100gmBW). Animals were sacrificed 3 months later, and blood and tissue samples were collected. Apoptotic changes were analyzed in epididymal spermatozoa and testis tissue by binding of annexin V apoptotic biomarker. A significant decline in the weight of testis, testosterone level, and sperm count was observed. Histopathological and apoptotic changes were observed in testis tissue. In epididymal sperms, the early apoptotic cells were observed by staining of annexin V-conjugated FITC and PI green fluorescence in spermatozoa head which indicated the damage of membrane and late apoptotic cells. These changes reduced significantly in Vitamin E-treated groups though were not found to be comparable to control animals. All these changes were attributed to disrupted spermatogenesis that would interfere with sperm formation. Thus, the study infers that BPA affects the apoptosis process in the testis and epididymal sperm that would interfere with its function and contribute to infertility, whereas Vitamin E-supplemented dose has a protective effect towards these changes, indicating its role in improving male fertility.

An update on the clinical trial of BNCT at the BMRR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, R.; Capala, J.; Chanana, A.D.

1999-09-01

Boron neutron capture therapy (BNCT) was proposed more than six decades ago. It is a binary treatment modality that requires selective delivery of a {sup 10}B-labeled compound to a tumor and slow neutron irradiation of the tumor-bearing tissues. In order to improve the penetration of the neutron beam, an epithermal neutron beam was developed at the Brookhaven Medical Research Reactor (BMRR). This epithermal neutron beam can deliver relatively high thermal neutron fluence at depth without severe skin damage. Boronophenylalanine-fructose (BPA-F), a nontoxic boron carrier, was found to preferentially accumulate in tumor cells following intravenous infusion in patients with GBM. Inmore » preclinical BNCT studies in rats bearing 9L gliosarcoma, BPA-mediated BNCT was shown to be more efficacious than photon irradiation. In 1994, improvements in the neutron beam and in the understanding of the radiobiology of BPA-mediated BNCT led to the initiation of BNCT trials for human GBM at BMRR using BPA-F and epithermal neutrons. The primary objective of the phase I/II clinical trial of BPA-mediated BNCT at BMRR is to evaluate the safety of the BPA-F-mediated BNCT using epithermal neutrons in patients with GBM at a series of escalating BNCT doses. An incidental objective is to evaluate the therapeutic effectiveness of BNCT at each dose level. For each dose escalation group, the average brain dose (ABD) is escalated, as well as the minimum tumor dose. In summary, the BNCT procedure employed in the phase I/II clinical trial of BPA-F-mediated BNCT for GBM at BNL was found to be safe in all patients. The palliation afforded by a single session of BNCT compares favorably with palliation provided by fractionated photon therapy and adjuvant chemotherapy. If no evidence of radiation-induced brain toxicity is found in the current protocol, BNCT radiation dose will be further escalated.« less

Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

NASA Astrophysics Data System (ADS)

Bose, Satya Ranjan

2000-06-01

An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large

L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

PubMed

Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. Copyright © 2015. Published by Elsevier Ireland Ltd.

Effects of BPA on global DNA methylation and global histone 3 lysine modifications in SH-SY5Y cells: An epigenetic mechanism linking the regulation of chromatin modifiying genes.

PubMed

Senyildiz, Mine; Karaman, Ecem Fatma; Bas, Serap Sancar; Pirincci, Pelin Arda; Ozden, Sibel

2017-10-01

Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the production of polycarbonate plastic and epoxy resins, resulting in high risk on human health. In present study we aimed to investigate the effects of BPA on global and gene specific DNA methylation, global histone modifications and regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH-SY5Y). Cells were treated with BPA at 0.1, 1 and 10μM concentrations for 48 and 96h. IC 50 value of BPA was determined as 183 and 129μM in SH-SY5Y cells after 24h by MTT and NRU tests, respectively. We observed significant alterations on the 5-mC% levels (1.3 fold) and 5-hmC% levels (1.67 fold) after 10μM of BPA for 96h. Significant decrease was identified in H3K9me3 and H3K9ac after 10μM of BPA for 96h while decrease was observed in H3K4me3 at 10μM of BPA for 48h. Alterations were observed in chromatin modifiying genes including G9a, EZH2, SETD8, SETD1A, HAT1, SIRT1, DNMT1, RIZ1 and Suv39h1 after 96h of BPA exposure. Taken together, this study suggests that BPA might modulate the epigenetic regulators which would be key molecular events in the toxicity of endocrine disrupting chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Soy but not bisphenol A (BPA) or the phytoestrogen genistin alters developmental weight gain and food intake in pregnant rats and their offspring

PubMed Central

Cao, Jinyan; Echelberger, Roger; Liu, Min; Sluzas, Emily; McCaffrey, Katherine; Buckley, Brian; Patisaul, Heather B.

2015-01-01

Endocrine disrupting compounds (EDCs) are hypothesized to promote obesity and early puberty but their interactive effects with hormonally active diets are poorly understood. Here we assessed individual and combinatorial effects of soy diet or the isoflavone genistein (GEN; administered as the aglycone genistin GIN) with bisphenol A (BPA) on body weight, ingestive behavior and female puberal onset in Wistar rats. Soy-fed dams gained less weight during pregnancy and, although they consumed more than dams on a soy-free diet during lactation, did not become heavier. Their offspring (both sexes), however, became significantly heavier (more pronounced in males) pre-weaning. Soy also enhanced food intake and accelerated female pubertal onset in the offspring. Notably, pubertal onset was also advanced in females placed on soy diet at weaning. Males exposed to BPA plus soy diet, but not BPA alone, had lighter testes. BPA had no independent effects. PMID:26216788

Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

DOE Office of Scientific and Technical Information (OSTI.GOV)

D.W. Nigg; William Bauer; Various Others

Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.

Amino Acid Proximities in Two Sup35 Prion Strains Revealed by Chemical Cross-linking*

PubMed Central

Wong, Shenq-Huey; King, Chih-Yen

2015-01-01

Strains of the yeast prion [PSI] are different folding patterns of the same Sup35 protein, which stacks up periodically to form a prion fiber. Chemical cross-linking is employed here to probe different fiber structures assembled with a mutant Sup35 fragment. The photo-reactive cross-linker, p-benzoyl-l-phenylalanine (pBpa), was biosynthetically incorporated into bacterially prepared recombinant Sup(1–61)-GFP, containing the first 61 residues of Sup35, followed by the green fluorescent protein. Four methionine substitutions and two alanine substitutions were introduced at fixed positions in Sup(1–61) to allow cyanogen bromide cleavage to facilitate subsequent mass spectrometry analysis. Amyloid fibers of pBpa and Met/Ala-substituted Sup(1–61)-GFP were nucleated from purified yeast prion particles of two different strains, namely VK and VL, and shown to faithfully transmit specific strain characteristics to yeast expressing the wild type Sup35 protein. Intra- and intermolecular cross-linking were distinguished by tandem mass spectrometry analysis on fibers seeded from solutions containing equal amounts of 14N- and 15N-labeled protein. Fibers propagating the VL strain type exhibited intra- and intermolecular cross-linking between amino acid residues 3 and 28, as well as intra- and intermolecular linking between 32 and 55. Inter- and intramolecular cross-linking between residues 32 and 55 were detected in fibers propagating the VK strain type. Adjacencies of amino acid residues in space revealed by cross-linking were used to constrain possible chain folds of different [PSI] strains. PMID:26265470

BPA exposure is associated with non-monotonic alteration in ESR1 promoter methylation in peripheral blood of men and shorter relative telomere length in peripheral blood of women.

PubMed

Awada, Z; Sleiman, F; Mailhac, A; Mouneimne, Y; Tamim, H; Zgheib, N K

2018-04-12

The aim of this study was to evaluate the potential association of urinary Bisphenol A (BPA) levels with estrogen receptor alpha (ESR1) promoter % methylation and relative telomere length in a sample of 482 participants. Urinary BPA concentration was measured using organic phase extraction followed by high performance liquid chromatography mass spectroscopy. Peripheral blood ESR1 promoter % methylation and relative telomere length were measured using direct bisulfite sequencing and real-time polymerase chain reaction, respectively. The mean ± SD urinary BPA concentration adjusted for urinary creatinine was 2.90 ± 4.81 (μg/g creatinine) with a median of 1.86 μg/g creatinine (min-max: BPA concentrations and ESR1 promoter % methylation in men. As a matter of fact, for the lowest tertile of ESR1 promoter % methylation, the OR and 95% CI of the middle and highest tertiles of urinary adjusted BPA were 2.54 (1.01-6.39) and 1.64 (0.55-4.86) when compared to the lowest BPA tertile, respectively. After adjustment for potential confounders, similar results remained in men and appeared in the whole cohort. As for relative telomere length, there was a significant trend whereby higher adjusted urinary BPA concentrations were significantly associated with shorter relative telomere length in females. For instance, for the shortest relative telomere length tertile, the OR and 95% CI of the middle and highest tertiles of urinary adjusted BPA were 2.91 (1.38-6.16) and 3.19 (1.57-6.49) when compared to the lowest BPA tertile, respectively. This trend remained significant after adjustment for potential confounders.

Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain.

PubMed

Chen, Wei-Nan; Chen, Chih-Cheng

2014-05-21

Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We prevented the intramuscular acid-induced hyperalgesia by pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1). The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2 days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice lacking substance P. Moreover, pretreatment with substance P in muscle mimicked the acid antinociceptive effect and prevented the hyperalgesia induced by next-day acid injection. Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model.

PubMed

Monti Hughes, A M; Pozzi, E C C; Thorp, S; Garabalino, M A; Farías, R O; González, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

2013-11-01

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model. Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

PubMed Central

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-01-01

Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID:27401411

ORAL BISPHENOL A (BPA) GIVEN TO RATS AT MODERATE DOSES IS ASSOCIATED WITH ERECTILE DYSFUNCTION, CAVERNOSAL LIPOFIBROSIS, AND ALTERATIONS OF GLOBAL GENE TRANSCRIPTION

PubMed Central

Kovanecz, I; Gelfand, R; Masouminia, M; Gharib, S; Segura, D; Vernet, D; Rajfer, J; Li, DK; Kannan, K; Gonzalez-Cadavid, NF

2013-01-01

Introduction Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor released from plastics is associated with erectile dysfunction (ED) in occupationally exposed workers. However, in rats, despite the induction of hypogonadism, apoptosis of the penile corporal smooth muscle, fat infiltration into the cavernosal tissue, and changes in global gene expression with the intraperitoneal administration of high dose BPA, ED was not observed. Aims We investigated whether BPA administered orally rather than intraperitoneally to rats for longer periods and lower doses will lead to ED. Main Outcomes Measures ED, histological, and biochemical markers in rat penile tissues. Methods 2.5-month old rats were given drinking water daily without and with BPA at 1 and 0.1 mg/kg/day. Two months later, erectile function was determined by cavernosometry (DIC) and electrical field stimulation (EFS) and serum levels of testosterone (T), estradiol (E2), and BPA were measured. Penile tissue sections were assayed by Masson (smooth muscle (SM)/collagen), Oil Red O (fat), TUNEL (apoptosis), immunohistochemistry for Oct 4 (stem cells), and α-SM actin/ calponin (SM and myofibroblasts), applying quantitative image analysis. Other markers were assayed by western blots. DNA microarrays/microRNA assays defined transcription profiles. Results Orally administered BPA did not affect body weight, but: 1) decreased serum T and E2; 2) reduced the EFS response and increased the DIC drop rate; 3) increased within the corporal tissue the presence of fat, myofibroblasts and apoptosis; 4) lowered the contents of SM and stem cells, but not nerve terminals; and 5) caused alterations of the transcriptional profiles for both mRNA and microRNAs within the penile shaft. Conclusions Long-term exposure of rats to oral BPA,caused a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to alterations within the corporal tissue that pose gene transcriptional changes related to

First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.a; National Research Council; Crivello, Martin

2011-01-01

Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ({sup 10}BPA) and for 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX ({sup 10}BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm {sup 10}B) + neutrons, (2) BOPP (10 ppm {sup 10}B) + neutrons, (3) neutrons alone, and (4) gammamore » rays ({sup 60}Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy ({+-}10%) (thermal neutrons flux = 7.5 10{sup 9} n/cm{sup 2} sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 {+-} 1.1 and 2.4 {+-} 0.6; CBE for BOPP: 8.0 {+-} 2.2 and 2.0 {+-} 1; CBE for BPA: 19.6 {+-} 3.7 and 3.5 {+-} 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3

Biomonitoring of bisphenol A, triclosan and perfluorooctanoic acid in hair samples of children and adults.

PubMed

Karzi, Vasiliki; Tzatzarakis, Manolis N; Vakonaki, Elena; Alegakis, Thanasis; Katsikantami, Ioanna; Sifakis, Stavros; Rizos, Apostolos; Tsatsakis, Aristidis M

2018-08-01

Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry. Low levels of exposure to PFOA were detected for children and adults at concentrations below limit of quantification. The mean concentration of BPA in children and adults was 20.6 and 16.6 pg mg -1 , while for TCS 275.2 and 687.0 pg mg -1 , respectively. Children were highly exposed to BPA relative to adults (P = .011) although adults had greater exposure to TCS (P = .003). Hair from girls had a greater burden of BPA (P = .06) compared to boys. Moreover, higher TCS levels were depicted for females in both examined groups (children P = .200 and adults P = .213) compared to males, but no statistical differences were observed. Significant differences were also observed between age groups (P = .0007) for TCS. No correlations were found between BPA or TCS levels and body mass index or dietary habits for both children and adults. Children have a greater exposure to BPA compared to adults, whereas exposure of adults to TCS seems to be higher than that in children and elderly people. Exposure to BPA occurs mainly via ingestion whereas exposure to TCS mainly via dermal absorption. Copyright © 2018 John Wiley & Sons, Ltd.

Investigation of the Effects of Subchronic Low Dose Oral Exposure to Bisphenol A (BPA) and Ethinyl Estradiol (EE) on Estrogen Receptor Expression in the Juvenile and Adult Female Rat Hypothalamus

PubMed Central

Rebuli, Meghan E.; Cao, Jinyan; Sluzas, Emily; Delclos, K. Barry; Camacho, Luísa; Lewis, Sherry M.; Vanlandingham, Michelle M.; Patisaul, Heather B.

2014-01-01

Concerns have been raised regarding the long-term impacts of early life exposure to the ubiquitous environmental contaminant bisphenol A (BPA) on brain organization. Because BPA has been reported to affect estrogen signaling, and steroid hormones play a critical role in brain sexual differentiation, there is also concern that BPA exposure could alter neural sex differences. Here, we examine the impact of subchronic exposure from gestation to adulthood to oral doses of BPA below the current no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day on estrogen receptor (ESR) expression in sexually dimorphic brain regions of prepubertal and adult female rats. The dams were gavaged daily with vehicle (0.3% carboxymethylcellulose), 2.5, 25, 260, or 2700 μg BPA/kg bw/day, or 0.5 or 5.0 μg ethinyl estradiol (EE)/kg bw/day from gestational day 6 until labor began. Offspring were then gavaged directly from the day after birth until the day before scheduled sacrifice on postnatal days 21 or 90. Using in situ hybridization, one or more BPA doses produced significant decreases in Esr1 expression in the juvenile female rat anteroventral periventricular nucleus (AVPV) of the hypothalamus and significant decreases in Esr2 expression in the adult female rat AVPV and medial preoptic area (MPOA), relative to vehicle controls. BPA did not simply reproduce EE effects, indicating that BPA is not acting solely as an estrogen mimic. The possible consequences of long-term changes in hypothalamic ESR expression resulting from subchronic low dose BPA exposure on neuroendocrine effects are discussed and being addressed in ongoing, related work. PMID:24752507

Cross-generational effects of parental low dose BPA exposure on the Gonadotropin-Releasing Hormone3 system and larval behavior in medaka (Oryzias latipes).

PubMed

Inagaki, T; Smith, N L; Sherva, K M; Ramakrishnan, S

2016-12-01

Growing evidence indicates that chronic exposure to Bisphenol A (BPA) may disrupt normal brain function and behavior mediated by gonadotropin-releasing hormone (GnRH) pathways. Previous studies have shown that low dose BPA (200ng/ml) exposure during embryogenesis altered development of extra-hypothalamic GnRH3 systems and non-reproductive locomotor behavior in medaka. Effects of parental low-dose BPA exposure on the development of GnRH3 systems and locomotor behavior of offspring are not well known. This study examines whether the neurophysiological and behavioral effects of BPA in parents (F0 generation) are carried over to their offspring (F1 generation) using stable transgenic medaka embryos/larvae with GnRH3 neurons tagged with green fluorescent protein (GFP). Parental fish were exposed to BPA (200ng/ml) for either life-long or different developmental time windows. Fertilized F1 eggs were collected and raised in egg/fish water with no environmental exposure to BPA. All experiments were performed on F1 embryos/larvae, which were grouped based on the following parental (F0) BPA exposure conditions - (i) Group 1 (G1): through life; (ii) G2: during embryogenesis and early larval development [1-14days post fertilization (dpf)]; (iii) G3: during neurogenesis (1-5dpf); and (iv) G4: during sex differentiation (5-14dpf). Embryos from unexposed vehicle treated parents served as controls (G0). G1 embryos showed significantly reduced survival rates and delayed hatching time compared to other groups, while G4 embryos hatched significantly earlier than all other groups. At 3 dpf, the GnRH3-GFP intensity was increased by 47% in G3 embryos and decreased in G4 embryos by 59% compared to controls. At 4dpf, G1 fish showed 42% increased intensity, while GFP intensity was reduced by 44% in G3 subjects. In addition, the mean brain size of G1, G3 and G4 embryos were smaller than that of control at 4dpf. At 20dpf, all larvae from BPA-treated parents showed significantly decreased

Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL.

PubMed

Yang, Jie; Chan, King Ming

2015-02-01

The toxic effects of three polybrominated diphenyl ether (PBDE) congeners (BDE-47, -99, and -209), tetrabromobisphenol A (TBBPA) and bisphenol A (BPA), were evaluated by determining their 24h and 96 h median lethal concentrations using a zebrafish liver cell line, ZFL. It was found that BDE-47, BDE-99 and TBBPA showed comparative cytotoxicity within the range of 1.2-4.2 μM, and were more toxic than BPA (367.1 μM at 24 h and 357.6 μM at 96 h). However, BDE-209 induced only 15% lethality with exposures up to 25 μM. The molecular stresses of BDE-47, -99, TBBPA and BPA involved in thyroid hormone (TH) homeostasis and hepatic metabolism were also investigated. Using a reporter gene system to detect zebrafish thyroid hormone receptor β (zfTRβ) transcriptional activity, the median effective concentration of triiodothyronine (T3) was determined to be 9.2×10(-11) M. BDE-47, BDE-99, TBBPA and BPA alone, however, did not exhibit zfTRβ agonistic activity. BPA displayed T3 (0.1 nM) induced zfTRβ antagonistic activity with a median inhibitory concentration of 19.3 μM. BDE-47, BDE-99 and TBBPA displayed no antagonistic effects of T3-induced zfTRβ activity. Target gene expressions were also examined under acute exposures. The significant inhibition of different types of deiodinases by all of the test chemicals indicated TH circulation disruption. All four chemicals, especially BPA, were able to affect transcripts of phase II hepatic metabolizing enzymes (UGT2A1, SULT1) in vitro. In conclusion, the zfTRβ reporter gene system developed here helps delineate an in vitro model to enable the analysis of the TH disruption effects of environmental pollutants in fish. BPA and the brominated compounds tested were able to disrupt the TH system at the gene expression level, probably through the deiodination pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines.

PubMed

Rossini, Andrés E; Dagrosa, Maria A; Portu, Agustina; Saint Martin, Giselle; Thorp, Silvia; Casal, Mariana; Navarro, Aimé; Juvenal, Guillermo J; Pisarev, Mario A

2015-01-01

In order to optimize the effectiveness of Boron Neutron Capture Therapy (BNCT), Relative Biological Effectiveness (RBE) and Compound Biological Effectiveness (CBE) were determined in two human melanoma cell lines, M8 and Mel-J cells, using the amino acid p-boronophenylalanine (BPA) as boron carrier. The effects of BNCT on the primary amelanotic cell line M8 and on the metastatic pigmented melanoma cell line Mel-J were studied using colony formation assay. The RBE values were determined using both a gamma ray source, and the neutron beam from the Nuclear Reactor of the National Atomic Energy Commission (RA-3). For the determination of the RBE, cells were irradiated with increasing doses of both sources, between 1 and 8 Gy; and for the determination of CBE factors, the cells were pre-incubated with BPA before irradiation. Afterwards, the cell surviving fraction (SF) was determined for each treatment. Marked differences were observed between both cell lines. Mel-J cells were more radioresistant than the M8 cell line. The clonogenic assays showed that for a SF of 1%, the RBE values were 1.3 for M8 cells and 1.5 for Mel-J cells. Similarly, the CBE values for a 1% SF were 2.1 for M8 and 3 for Mel-J cell lines. For the endpoint of 0.1% of SF the RBE values obtained were 1.2 for M8 and 1.4 for Mel-J cells. Finally, CBE values calculated for a 0.1% were 2 and 2.6 for M8 and Mel-J cell lines respectively. In order to estimate the uptake of the non-radioactive isotope Boron 10 ((10)B), a neutron induced autoradiographic technique was performed showing discrepancies in (10)B uptake between both cell lines. These obtained in vitro results are the first effectiveness factors determined for human melanoma at the RA-3 nuclear reactor and show that BNCT dosimetry planning for patients could be successfully performed using these new factors.

40 CFR 180.202 - p-Chlorophenoxyacetic acid; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false p-Chlorophenoxyacetic acid; tolerances... Tolerances § 180.202 p-Chlorophenoxyacetic acid; tolerances for residues. (a) General. A tolerance is established for the combined residues of the plant regulator p-chlorophenoxyacetic acid and its metabolite p...

40 CFR 180.202 - p-Chlorophenoxyacetic acid; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false p-Chlorophenoxyacetic acid; tolerances... Tolerances § 180.202 p-Chlorophenoxyacetic acid; tolerances for residues. (a) General. A tolerance is established for the combined residues of the plant regulator p-chlorophenoxyacetic acid and its metabolite p...

40 CFR 180.202 - p-Chlorophenoxyacetic acid; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false p-Chlorophenoxyacetic acid; tolerances... Tolerances § 180.202 p-Chlorophenoxyacetic acid; tolerances for residues. (a) General. A tolerance is established for the combined residues of the plant regulator p-chlorophenoxyacetic acid and its metabolite p...

Isolation of bisphenol A-tolerant/degrading Pseudomonas monteilii strain N-502.

PubMed

Masuda, Midori; Yamasaki, Yoshiki; Ueno, Shun; Inoue, Akira

2007-03-01

Bisphenol A (BPA) is a highly biotoxic compound that kills many microorganisms at a low concentration (1,000 ppm). We isolated BPA-tolerant/degrading Pseudomonas monteilii strain N-502 from about 1,000 samples collected from a field, sewage, and pond water. The isolated strain had strong BPA tolerance and high BPA-degrading activity. This strain was able to grow in a minimum medium containing BPA as the sole carbon source. Strain N-502 is an aerobic, motile, gram-negative, nonspore-forming, rod-shaped bacterium and was identified as P. monteilii, based on 16 S rRNA gene analysis. Strain N-502 completely degraded BPA 500 ppm in a 10-day, in culture system and was able to degrade BPA 100 ppm in a 2-h resting cell system. This strain also showed potent ability to degrade BPA 500 and 1,000 ppm in the resting cell system. Moreover, the initial BPA degradation rate was accelerated with the addition of Ca(2+), Mg(2+), and folic acid.

Growth of Azotobacter chroococcum in chemically defined media containing p-hydroxybenzoic acid and protocatechuic acid.

PubMed

Juarez, B; Martinez-Toledo, M V; Gonzalez-Lopez, J

2005-06-01

Growth and utilization of different phenolic acids present in olive mill wastewater (OMW) by Azotobacter chroococcum were studied in chemically defined media. Growth and utilization of phenolic acids were only detected when the microorganism was cultured on p-hydroxybenzoic acid at concentration from 0.01% to 0.5% (w/v) and protocatechuic acid at concentration from 0.01% to 0.3% (w/v) as sole carbon sources suggesting that only these phenolic compounds could be utilized as a carbon source by A. chroococcum. Moreover when culture media were added with a mixture of 0.3% of protocatechuic acid and 0.3% p-hydroxybenzoic acid, the microorganism degradated in first place protocatechuic acid and once the culture medium was depleted of this compound, the degradation of p-hydroxybenzoic acid commenced very fast.

Photoaffinity Labeling of Ras Converting Enzyme using Peptide Substrates that Incorporate Benzoylphenylalanine (Bpa) Residues: Improved Labeling and Structural Implications

PubMed Central

Kyro, Kelly; Manandhar, Surya P.; Mullen, Daniel; Schmidt, Walter K.; Distefano, Mark D.

2012-01-01

Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photoaffinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p-benzoyl-L-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design. PMID:22079863

Effect of nitrate, carbonate/bicarbonate, humic acid, and H2O2 on the kinetics and degradation mechanism of Bisphenol-A during UV photolysis.

PubMed

Kang, Young-Min; Kim, Moon-Kyung; Zoh, Kyung-Duk

2018-08-01

In this study, the effects of natural water components (nitrate, carbonate/bicarbonate, and humic acid) on the kinetics and degradation mechanisms of bisphenol A (BPA) during UV-C photolysis and UV/H 2 O 2 reaction were examined. The presence of NO 3 - (0.04-0.4 mM) and CO 3 2- /HCO 3 - (0.4-4 mM) ions increased BPA degradation during UV photolysis. Humic acid less than 3 mg/L promoted BPA degradation, but greater than 3 mg/L of humic acid inhibited BPA degradation. During the UV/H 2 O 2 reaction, all water matrix components acted as radical scavengers in the order of humic acid > CO 3 2- /HCO 3 -  > NO 3 - . All of the degradation reactions agreed with the pseudo-first-order kinetics. While eight byproducts (m/z = 122, 136, 139, 164, 181, 244, 273, 289) were identified in UV-C/NO 3 - photolysis reaction, four (m/z = 122, 136, 164, 244) and three byproducts (m/z = 122, 136, 164) were observed during UV-C/NO 3 - /CO 3 2- /HCO 3 - and UV-C/CO 3 2- /HCO 3 - reactions. Nitrogenated and hydrogenated byproducts were first observed during the UV-C/NO 3 - photolysis, but only hydrogenated byproducts as adducts were detected during the UV-C/NO 3 - /CO 3 2- /HCO 3 - photolysis. Nitrogenated and hydrogenated byproducts were formed in the early stage of degradation by OH or NO 2 radicals, and these byproducts were subsequently degraded into smaller compounds with further reaction during UV-C/NO 3 - and UV-C/NO 3 - /CO 3 2- /HCO 3 - reactions. In contrast, BPA was directly degraded into smaller compounds by β-scission of the isopropyl group by CO 3 - /HCO 3 radicals during UV-C/CO 3 2- /HCO 3 - reaction. Our results imply that the water components can change the degradation mechanism of BPA during UV photolysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spectroscopic studies on the antioxidant activity of p-coumaric acid

NASA Astrophysics Data System (ADS)

Kiliç, Ismail; Yeşiloğlu, Yeşim

2013-11-01

p-coumaric acid (4-hydroxycinnamic acid), a phenolic acid, is a hydroxyl derivative of cinnamic acid. It decreases low density lipoprotein (LDL) peroxidation and reduces the risk of stomach cancer. In vitro radical scavenging and antioxidant capacity of p-coumaric acid were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2‧-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. p-Coumaric acid inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and ascorbic acid displayed 66.8%, 69.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, p-coumaric acid had an effective DPPHrad scavenging, ABTSrad + scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that p-coumaric acid can be used in the pharmacological and food industry because of these properties.

Nine co-localized cytochrome P450 genes of the CYP2N, CYP2AD, and CYP2P gene families in the mangrove killifish Kryptolebias marmoratus genome: Identification and expression in response to B[α]P, BPA, OP, and NP.

PubMed

Puthumana, Jayesh; Kim, Bo-Mi; Jeong, Chang-Bum; Kim, Duck-Hyun; Kang, Hye-Min; Jung, Jee-Hyun; Kim, Il-Chan; Hwang, Un-Ki; Lee, Jae-Seong

2017-06-01

The CYP2 genes are the largest and most diverse cytochrome P450 (CYP) subfamily in vertebrates. We have identified nine co-localized CYP2 genes (∼55kb) in a new cluster in the genome of the highly resilient ecotoxicological fish model Kryptolebias marmoratus. Molecular characterization, temporal and tissue-specific expression pattern, and response to xenobiotics of these genes were examined. The CYP2 gene clusters were characterized and designated CYP2N22-23, CYP2AD12, and CYP2P16-20. Gene synteny analysis confirmed that the cluster in K. marmoratus is similar to that found in other teleost fishes, including zebrafish. A gene duplication event with diverged catalytic function was observed in CYP2AD12. Moreover, a high level of divergence in expression was observed among the co-localized genes. Phylogeny of the cluster suggested an orthologous relationship with similar genes in zebrafish and Japanese medaka. Gene expression analysis showed that CYP2P19 and CYP2N20 were consecutively expressed throughout embryonic development, whereas CYP2P18 was expressed in all adult tissues, suggesting that members of each CYP2 gene family have different physiological roles even though they are located in the same cluster. Among endocrine-disrupting chemicals (EDCs), benzo[α]pyrene (B[α]P) induced expression of CYP2N23, bisphenol A (BPA) induced CYP2P18 and CYP2P19, and 4-octylphenol (OP) induced CYP2AD12, but there was no significant response to 4-nonylphenol (NP), implying differential catalytic roles of the enzyme. In this paper, we identify and characterize a CYP2 gene cluster in the mangrove killifish K. marmoratus with differing catalytic roles toward EDCs. Our findings provide insights on the roles of nine co-localized CYP2 genes and their catalytic functions for better understanding of chemical-biological interactions in fish. Copyright © 2017 Elsevier B.V. All rights reserved.

The Future Impact of Wind on BPA Power System Load Following and Regulation Requirements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarov, Yuri V.; Lu, Shuai; McManus, Bart

Wind power is growing in a very fast pace as an alternative generating resource. As the ratio of wind power over total system capacity increases, the impact of wind on various system aspects becomes significant. This paper presents a methodology to study the future impact of wind on BPA power system load following and regulation requirements. Existing methodologies for similar analysis include dispatch model simulation and standard deviation evaluation on load and wind data. The methodology proposed in this paper uses historical data and stochastic processes to simulate the load balancing processes in the BPA power system. It mimics themore » actual power system operations therefore the results are close to reality yet the study based on this methodology is convenient to perform. The capacity, ramp rate and ramp duration characteristics are extracted from the simulation results. System load following and regulation capacity requirements are calculated accordingly. The ramp rate and ramp duration data obtained from the analysis can be used to evaluate generator response or maneuverability requirement and regulating units’ energy requirement, respectively.« less

Spectroscopic studies on the antioxidant activity of p-coumaric acid.

PubMed

Kiliç, Ismail; Yeşiloğlu, Yeşim

2013-11-01

p-coumaric acid (4-hydroxycinnamic acid), a phenolic acid, is a hydroxyl derivative of cinnamic acid. It decreases low density lipoprotein (LDL) peroxidation and reduces the risk of stomach cancer. In vitro radical scavenging and antioxidant capacity of p-coumaric acid were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe(2+)) chelating activity and ferric ions (Fe(3+)) reducing ability. p-Coumaric acid inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45μg/mL concentration. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and ascorbic acid displayed 66.8%, 69.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, p-coumaric acid had an effective DPPH scavenging, ABTS(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that p-coumaric acid can be used in the pharmacological and food industry because of these properties. Copyright © 2013 Elsevier B.V. All rights reserved.

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

PubMed Central

Morris, G M; Smith, D R; Patel, H; Chandra, S; Morrison, G H; Hopewell, J W; Rezvani, M; Micca, P L; Coderre, J A

2000-01-01

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as

[Degradation kinetics of chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid at neutral and alkaline pH values].

PubMed

Zhu, Peng; Miao, Xiao-lei; Chen, Yong

2016-01-01

The degradation kinetics of chlorogenic acid (5-CQA), cryptochlorogenic acid (4-CQA), and neochlorogenic acid (3-CQA) in aqueous solution at 37 degrees C and different pH values (7.05, 7.96, 9.25) were investigated in the present work. The results indicated that 3-, 4- and 5-CQA tended to remain stable in acidic pH circumstance, and unstable in neutral and alkaline pH circumstance. With the increase of the alkalinity, the degradation of 3-, 4- and 5-CQA was increased leading to a less amount of total CQA and was satisfactorily described by the Weibull equation. Meanwhile, caffeic acid was not detected after the degradation of CQA. Moreover, the degradation of 3-CQA and 5-CQA tended to be converted to 4-CQA, and the degradation of 4-CQA tended to be converted to 3-CQA rather than 5-CQA. The comparison of the degradation kinetics parameters of 3-, 4- and 5-CQA at neutral and alkaline pH values showed that the orders of the rate constant (k) values were 4-CQA > 3-CQA > 5-CQA, while the orders of the degradation half life (t½) values were 4-CQA < 3-CQA < 5-CQA, indicating the orders of the stabilities of 3-, 4- and 5-CQA at 37 degrees C and neutral and alkaline pH values were 4-CQA < 3-CQA < 5-CQA.

Expression of stress response HSP70 gene in Asian paddle crabs, Charybdis japonica, exposure to endocrine disrupting chemicals, bisphenol A (BPA) and 4-nonylphenol (NP)

NASA Astrophysics Data System (ADS)

Park, Kiyun; Kwak, Ihn-Sil

2013-06-01

The Asian paddle crab, Charybdis japonica, is a potential bio-indicator reflecting marine sediment toxicity as well as a commercially important species living along coastal areas in Korea. This study investigated its stress response by looking at the heat shock protein (HSP70) gene of C. japonica when the organism is exposed to bisphenol A (BPA) and 4-nonylphenol (NP). We characterized partial sequence of HSP70 as the stressresponse gene of C. japonica. The nucleotide sequence of C. japonica HSP70 is over 90% homologous with the corresponding gene of other crabs. Phylogenetic tree analysis revealed a close relationship between C. japonica HSP70 and HSP70 in other species of lobster and shrimps. HSP70 mRNA transcripts were detected in all the examined tissues of C. japonica, with the highest level in gills, the organ that most frequently came into contact with the external BPA or NP-laden water. As no reference data were available for C. japonica crab exposure, the BPA and NP 24-h LC50 values have not been previously determined. The expression of the C. japonica HSP70 gene to various BPA or NP concentrations during short and longer times was assessed. Gene expression was significantly induced in concentration- and time-dependent manners after BPA or NP exposures. These results support the postulation that crab C. japonica HSP70 could be a potential stress response molecular marker to monitor marine ecosystems.

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

PubMed

Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

2017-08-01

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

Biotransformation of glyceryl trinitrate (GTN) in isolated bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-03-01

A proposed mechanism of GTN-induced vasodilation requires biotransformation of GTN to glyceryl dinitrate (GDN). They have previously shown that GTN is metabolized to GDN during relaxation of isolated rabbit aorta. The authors have extended this study to include BPA and BPV and to determine if their sensitivity to GTN correlates with their ability to metabolize GTN. Strips of BPA and BPV were contracted submaximally with KCl and then incubated with 0.5 ..mu..M /sup 14/C-GTN for 2 min. GTN-induced relaxation of these vessels was monitored and tissue GTN and metabolite concentrations were measured. Data are presented which support the above hypothesismore » that GTN biotransformation and relaxation occur together in vascular smooth muscle; however, there appear to be factors other than extent of GTN biotransformation that account for the difference in sensitivity to GTN of the artery and vein.« less

Grape skins (Vitis vinifera L.) catalyze the in vitro enzymatic hydroxylation of p-coumaric acid to caffeic acid.

PubMed

Arnous, Anis; Meyer, Anne S

2009-12-01

The ability of grape skins to catalyze in vitro conversion of p-coumaric acid to the more potent antioxidant caffeic acid was studied. Addition of different concentrations of p-coumaric to red grape skins (Cabernet Sauvignon) resulted in formation of caffeic acid. This caffeic acid formation (Y) correlated positively and linearly to p-coumaric acid consumption (X): Y = 0.5 X + 9.5; R (2) = 0.96, P < 0.0001. The kinetics of caffeic acid formation with time in response to initial p-coumaric acid levels and at different grape skin concentrations, indicated that the grape skins harboured an o-hydroxylation activity, proposedly a monophenol- or a flavonoid 3'-monooxygenase activity (EC 1.14.18.1 or EC 1.14.13.21). The K (m) of this crude o-hydroxylation activity in the red grape skin was 0.5 mM with p-coumaric acid.

Identification of amino acids in the N-terminal SH2 domain of phospholipase C gamma 1 important in the interaction with epidermal growth factor receptor.

PubMed

Gergel, J R; McNamara, D J; Dobrusin, E M; Zhu, G; Saltiel, A R; Miller, W T

1994-12-13

Photoaffinity labeling and site-directed mutagenesis have been used to identify amino acid residues of the phospholipase C gamma 1 (PLC gamma 1) N-terminal SH2 domain involved in recognition of the activated epidermal growth factor receptor (EGFR). The photoactive amino acid p-benzoylphenylalanine (Bpa) was incorporated into phosphotyrosine-containing peptides derived from EGFR autophosphorylation sites Tyr992 and Tyr1068. Irradiation of these labels in the presence of SH2 domains showed cross-linking which was time-dependent and specific; labeling was inhibited with non-Bpa-containing peptides from EGFR in molar excess. The phosphotyrosine residue on the peptides was important for SH2 recognition, as dephosphorylated peptides did not cross-link. Radiolabeled peptides were used to identify sites of cross-linking to the N-terminal SH2 of PLC gamma 1. Bpa peptide-SH2 complexes were digested with trypsin, and radioactive fragments were purified by HPLC and analyzed by Edman sequencing. These experiments showed Arg562 and an additional site in the alpha A-beta B region of the SH2 domain, most likely Glu587, to be labeled by the Tyr992-derived peptide. Similar analysis of the reaction with the Tyr1068-derived photoaffinity label identified Leu653 as the cross-linked site. Mutation of the neighboring residues of Glu587 decreased photo-cross-linking, emphasizing the importance of this region of the molecule for recognition. These results are consistent with evidence from the v-Src crystal structure and implicate the loop spanning residues Gln640-Ser654 of PLC gamma 1 in specific recognition of phosphopeptides.

Low Probability Tail Event Analysis and Mitigation in BPA Control Area: Task 2 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Shuai; Makarov, Yuri V.; McKinstry, Craig A.

Task report detailing low probability tail event analysis and mitigation in BPA control area. Tail event refers to the situation in a power system when unfavorable forecast errors of load and wind are superposed onto fast load and wind ramps, or non-wind generators falling short of scheduled output, causing the imbalance between generation and load to become very significant.

Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

PubMed

Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

2016-11-17

The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation

PubMed Central

Angle, Brittany M.; Do, Rylee Phuong; Ponzi, Davide; Stahlhut, Richard W.; Drury, Bertram E.; Nagel, Susan C.; Welshons, Wade V.; Besch-Williford, Cynthia L; Palanza, Paola; Parmigiani, Stefano; vom Saal, Frederick S.; Taylor, Julia A.

2013-01-01

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000 μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0–24h),we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose–response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes. PMID:23892310

Effects of bisphenol A (BPA) on brain-specific expression of cyp19a1b gene in swim-up fry of Labeo rohita.

PubMed

Gupta, Shreyasi; Guha, Payel; Majumder, Suravi; Pal, Puja; Sen, Koushik; Chowdhury, Piyali; Chakraborty, Arindam; Panigrahi, Ashis Kumar; Mukherjee, Dilip

2018-07-01

Estrogen regulates numerous developmental and physiological processes and effects are mediated mainly by estrogenic receptors (ERs), which function as ligand-regulated transcription factor. ERs can be activated by many different types endocrine disrupting chemicals (EDCs) and interfere with behaviour and reproductive potential of living organism. Estrogenic regulation of membrane associated G protein-coupled estrogen receptor, GPER activity has also been reported. Bisphenol A (BPA), a ubiquitous endocrine disruptor is present in many household products, has been linked to many adverse effect on sexual development and reproductive potential of wild life species. The present work is aimed to elucidate how an environmentally pervasive chemical BPA affects in vivo expression of a known estrogen target gene, cyp19a1b in the brain, and a known estrogenic biomarker, vitellogenin (Vg) in the whole body homogenate of 30 days post fertilization (dpf) swim-up fry of Labeo rohita. We confirm that, like estrogen, the xenoestrogen BPA exposure for 5-15 days induces strong overexpression of cyp19a1b, but not cyp19a1a mRNA in the brain and increase concentration of vitellogenin in swim-up fry. BPA also induces strong overexpression of aromatase B protein and aromatase activity in brain. Experiments using selective modulators of classical ERs and GPER argue that this induction is largely through nuclear ERs, not through GPER. Thus, BPA has the potential to elevate the levels of aromatase and thereby, levels of endogenous estrogen in developing brain. These results indicate that L. rohita swim-up fry can be used to detect environmental endocrine disruptors either using cyp19a1b gene expression or vitellogenin induction. Copyright © 2018 Elsevier Inc. All rights reserved.

A comparative evaluation of different types of microbial electrolysis desalination cells for malic acid production.

PubMed

Liu, Guangli; Zhou, Ying; Luo, Haiping; Cheng, Xing; Zhang, Renduo; Teng, Wenkai

2015-12-01

The aim of this study was to investigate different microbial electrolysis desalination cells for malic acid production. The systems included microbial electrolysis desalination and chemical-production cell (MEDCC), microbial electrolysis desalination cell (MEDC) with bipolar membrane and anion exchange membrane (BP-A MEDC), MEDC with bipolar membrane and cation exchange membrane (BP-C MEDC), and modified microbial desalination cell (M-MDC). The microbial electrolysis desalination cells performed differently in terms of malic acid production and energy consumption. The MEDCC performed best with the highest malic acid production rate (18.4 ± 0.6 mmol/Lh) and the lowest energy consumption (0.35 ± 0.14 kWh/kg). The best performance of MEDCC was attributable to the neutral pH condition in the anode chamber, the lowest internal resistance, and the highest Geobacter percentage of the anode biofilm population among all the reactors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Is container type the biggest predictor of trace element and BPA leaching from drinking water bottles?

PubMed

Rowell, Candace; Kuiper, Nora; Preud'Homme, Hugues

2016-07-01

The knowledge-base of bottled water leachate is highly contradictory due to varying methodologies and limited multi-elemental and/or molecular analyses; understanding the range of contaminants and their pathways is required. This study determined the leaching potential and leaching kinetics of trace elements, using consistent comprehensive quantitative and semi-quantitative (79 elements total) analyses, and BPA, using isotopic dilution and MEPS pre-concentration with UHPLC-ESI-QTOF. Statistical methods were used to determine confounders and predictors of leaching and human health risk throughout 12days of UV exposure and after exposure to elevated temperature. Various types of water were used to assess the impact of water quality. Results suggest Sb leaching is primarily dependent upon water quality, not container type. Bottle type is a predictor of elemental leaching for Pb, Ba, Cr, Cu, Mn and Sr; BPA was detected in samples from polycarbonate containers. Health risks from the consumption of bottled water increase after UV exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Catabolism of coniferyl aldehyde, ferulic acid and p-coumaric acid by Saccharomyces cerevisiae yields less toxic products.

PubMed

Adeboye, Peter Temitope; Bettiga, Maurizio; Aldaeus, Fredrik; Larsson, Per Tomas; Olsson, Lisbeth

2015-09-21

Lignocellulosic substrates and pulping process streams are of increasing relevance to biorefineries for second generation biofuels and biochemical production. They are known to be rich in sugars and inhibitors such as phenolic compounds, organic acids and furaldehydes. Phenolic compounds are a group of aromatic compounds known to be inhibitory to fermentative organisms. It is known that inhibition of Sacchromyces cerevisiae varies among phenolic compounds and the yeast is capable of in situ catabolic conversion and metabolism of some phenolic compounds. In an approach to engineer a S. cerevisiae strain with higher tolerance to phenolic inhibitors, we selectively investigated the metabolic conversion and physiological effects of coniferyl aldehyde, ferulic acid, and p-coumaric acid in Saccharomyces cerevisiae. Aerobic batch cultivations were separately performed with each of the three phenolic compounds. Conversion of each of the phenolic compounds was observed on time-based qualitative analysis of the culture broth to monitor various intermediate and final metabolites. Coniferyl aldehyde was rapidly converted within the first 24 h, while ferulic acid and p-coumaric acid were more slowly converted over a period of 72 h. The conversion of the three phenolic compounds was observed to involved several transient intermediates that were concurrently formed and converted to other phenolic products. Although there were several conversion products formed from coniferyl aldehyde, ferulic acid and p-coumaric acid, the conversion products profile from the three compounds were similar. On the physiology of Saccharomyces cerevisiae, the maximum specific growth rates of the yeast was not affected in the presence of coniferyl aldehyde or ferulic acid, but it was significantly reduced in the presence of p-coumaric acid. The biomass yields on glucose were reduced to 73 and 54 % of the control in the presence of coniferyl aldehyde and ferulic acid, respectively, biomass yield

40 CFR 721.10412 - Phosphonic acid ester (generic) (P-07-706).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid ester (generic) (P-07... Specific Chemical Substances § 721.10412 Phosphonic acid ester (generic) (P-07-706). (a) Chemical substance... phosphonic acid ester (PMN P-07-706) is subject to reporting under this section for the significant new uses...

40 CFR 721.10412 - Phosphonic acid ester (generic) (P-07-706).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid ester (generic) (P-07... Specific Chemical Substances § 721.10412 Phosphonic acid ester (generic) (P-07-706). (a) Chemical substance... phosphonic acid ester (PMN P-07-706) is subject to reporting under this section for the significant new uses...

40 CFR 721.10412 - Phosphonic acid ester (generic) (P-07-706).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid ester (generic) (P-07... Specific Chemical Substances § 721.10412 Phosphonic acid ester (generic) (P-07-706). (a) Chemical substance... phosphonic acid ester (PMN P-07-706) is subject to reporting under this section for the significant new uses...

Sulfuric acid induces airway hyperresponsiveness to substance P in the guinea pig.

PubMed

Stengel, P W; Bendele, A M; Cockerham, S L; Silbaugh, S A

1993-01-01

We investigated whether sulfuric acid inhalation would cause hyperresponsiveness to substance P. Guinea pigs became dyspneic during a 1 h sulfuric acid exposure, but recovered by 24 h when they were challenged with substance P or histamine aerosols. Eight minutes after the start of challenge, animals were killed and excised lung gas volumes measured. Sulfuric acid slightly increased histamine responsiveness compared to controls. However, sulfuric acid caused a much more pronounced leftward shift in the dose response to substance P. Coadministration of the neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sulfuric acid-related hyperresponsiveness to substance P. By 72 h, sensitization to substance P was absent. Histological evaluation of sulfuric acid-treated lungs revealed mild alveolitis at 24 h, but not at 72 h. We conclude that sulfuric acid produces a marked sensitization to substance P. Inactivation of NEP does not appear to account for this effect.

Low-pH production of D-lactic acid using newly isolated acid tolerant yeast Pichia kudriavzevii NG7.

PubMed

Park, Hyun Joo; Bae, Jung-Hoon; Ko, Hyeok-Jin; Lee, Sun-Hee; Sung, Bong Hyun; Han, Jong-In; Sohn, Jung-Hoon

2018-06-13

Lactic acid is a platform chemical for the sustainable production of various materials. To develop a robust yeast platform for low-pH production of D-lactic acid, an acid-tolerant yeast strain was isolated from grape skins and named Pichia kudriavzevii NG7 by ribosomal RNA sequencing. This strain was able to grow at pH 2.0 and 50°C. For the commercial application of P. kudriavzevii NG7 as a lactic acid producer, the ethanol fermentation pathway was redirected to lactic acid by replacing pyruvate decarboxylase 1 gene (PDC1) with D-lactate dehydrogenase gene (D-LDH) derived from Lactobacillus plantarum. To enhance lactic acid tolerance, this engineered strain was adapted to high lactic acid concentrations, and a new transcriptional regulator, PAR1, responsible for acid tolerance, was identified by whole-genome resequencing. The final engineered strain produced 135 g/L and 154 g/L of D-lactic acid with productivity over 3.66 g/L/h at pH 3.6 and 4.16 g/L/h at pH 4.7, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of steam explosion-assisted extraction on phenolic acid profiles and antioxidant properties of wheat bran.

PubMed

Liu, Liya; Zhao, Mengli; Liu, Xingxun; Zhong, Kui; Tong, Litao; Zhou, Xianrong; Zhou, Sumei

2016-08-01

The majority of phenolic acids in wheat bran are bound to the cell walls. Hence, a high proportion of phenolic acids cannot be extracted with conventional extraction methods. This study aimed to investigate the efficiency of steam explosion pre-treatment in increasing the extractability of phenolic compounds from wheat bran. Bound phenolic acids (BPA) can be released by steam explosion-assisted extraction. Within the experimental range, soluble free phenolic acids (FPA) and soluble conjugated phenolic acids (CPA) increased gradually with residence time and temperature. After steam explosion at 215 °C for 120 s, the total FPA and CPA reached 6671.8 and 2578.6 µg GAE g(-1) bran, respectively, which was about 39-fold and seven-fold higher than that of the untreated sample. Ferulic acid, the major individual phenolic acids in bran, increased from 55.7 to 586.3 µg g(-1) for FPA, and from 44.9 to 1108.4 µg g(-1) for CPA. The antioxidant properties of FPA and CPA extracts were significantly improved after treated. Correlation analysis indicated that the antioxidant capacity was in close relationship with phenolic content in FPA and CPA. Steam explosion pre-treatment could be effectively used to release of BPA and enhance the antioxidant capacity of wheat bran. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Aromatic Hydroxylation of Salicylic Acid and Aspirin by Human Cytochromes P450

PubMed Central

Bojić, Mirza; Sedgeman, Carl A.; Nagy, Leslie D.; Guengerich, F. Peter

2015-01-01

Aspirin (acetylsalicylic acid) is a well-known and widely-used analgesic. It is rapidly deacetylated to salicylic acid, which forms two hippuric acids—salicyluric acid and gentisuric acid—and two glucuronides. The oxidation of aspirin and salicylic acid has been reported with human liver microsomes, but data on individual cytochromes P450 involved in oxidation is lacking. In this study we monitored oxidation of these compounds by human liver microsomes and cytochrome P450 (P450) using UPLC with fluorescence detection. Microsomal oxidation of salicylic acid was much faster than aspirin. The two oxidation products were 2,5-dihydroxybenzoic acid (gentisic acid, documented by its UV and mass spectrum) and 2,3-dihydroxybenzoic acid. Formation of neither product was inhibited by desferrioxamine, suggesting a lack of contribution of oxygen radicals under these conditions. Although more liphophilic, aspirin was oxidized less efficiently, primarily to the 2,5-dihydroxy product. Recombinant human P450s 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 all catalyzed the 5-hydroxylation of salicylic acid. Inhibitor studies with human liver microsomes indicated that all six of the previously mentioned P450s could contribute to both the 5- and 3-hydroxylation of salicylic acid and that P450s 2A6 and 2B6 have contributions to 5-hydroxylation. Inhibitor studies indicated that the major human P450 involved in both 3- and 5-hydroxylation of salicylic acid is P450 2E1. PMID:25840124

Titratable acidity of beverages influences salivary pH recovery.

PubMed

Tenuta, Livia Maria Andaló; Fernández, Constanza Estefany; Brandão, Ana Carolina Siqueira; Cury, Jaime Aparecido

2015-01-01

A low pH and a high titratable acidity of juices and cola-based beverages are relevant factors that contribute to dental erosion, but the relative importance of these properties to maintain salivary pH at demineralizing levels for long periods of time after drinking is unknown. In this crossover study conducted in vivo, orange juice, a cola-based soft drink, and a 10% sucrose solution (negative control) were tested. These drinks differ in terms of their pH (3.5 ± 0.04, 2.5 ± 0.05, and 5.9 ± 0.1, respectively) and titratable acidity (3.17 ± 0.06, 0.57 ± 0.04 and < 0.005 mmols OH- to reach pH 5.5, respectively). Eight volunteers with a normal salivary flow rate and buffering capacity kept 15 mL of each beverage in their mouth for 10 s, expectorated it, and their saliva was collected after 15, 30, 45, 60, 90, and 120 s. The salivary pH, determined using a mini pH electrode, returned to the baseline value at 30 s after expectoration of the cola-based soft drink, but only at 90 s after expectoration of the orange juice. The salivary pH increased to greater than 5.5 at 15 s after expectoration of the cola drink and at 30 s after expectoration of the orange juice. These findings suggest that the titratable acidity of a beverage influences salivary pH values after drinking acidic beverages more than the beverage pH.

Acidic pH modulation of Na+ channels in trigeminal mesencephalic nucleus neurons.

PubMed

Kang, In-Sik; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

2016-12-07

Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. However, acidic pH (pH 6.0) had a minor effect on the inactivation kinetics of voltage-gated Na channels. Less sensitivity of voltage-gated Na channels to acidic pH may allow Vmes neurons to transduce the precise proprioceptive information even under acidic pH conditions.

Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors

PubMed Central

Barth, Rolf F.; Yang, Weilian; Wu, Gong; Swindall, Michele; Byun, Youngjoo; Narayanasamy, Sureshbabu; Tjarks, Werner; Tordoff, Kevin; Moeschberger, Melvin L.; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

2008-01-01

The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl] thymidine, designated N5–2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(−) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of 10B-enriched N5–2OH were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15× reduction in tumor volume compared with TK1(−) controls. Based on these favorable results, BNCT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5–2OH by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 ± 7.2 days, 35.0 ± 3.3days, and 52.9 ± 8.9 days, respectively, for animals that received N5–2OH, BPA, or both. The differences between the survival plots of rats that received N5–2OH and BPA alone were highly significant (P = 0.0003). These data provide proof-of-principle that a 3CTA can function as a boron delivery agent for NCT. Further studies are planned to design and synthesize 3CTAs with enhanced chemical and biological properties, and increased therapeutic efficacy. PMID:18981415

Development of smart delivery system for ascorbic acid using pH-responsive P(MAA-co-EGMA) hydrogel microparticles.

PubMed

Lee, Eunmi; Kim, Kyusik; Choi, Moonjae; Lee, Youngmoo; Park, Jin-Won; Kim, Bumsang

2010-11-01

pH-Responsive P(MAA-co-EGMA) hydrogel microparticles were prepared and their feasibility as intelligent delivery carriers was evaluated. P(MAA-co-EGMA) hydrogel microparticles were synthesized via dispersion photopolymerization. There was a drastic change in the swelling ratio of P(MAA-co-EGMA) microparticles at a pH of ~ 5 and, as the amount of MAA in the hydrogel increased, the swelling ratio increased at a pH above 5. The loading efficiency of the ascorbic acid into the hydrogel was affected more by the degree of swelling of the hydrogel than the electrostatic interaction between the hydrogel and the loaded ascorbic acid. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-sensitive release behavior. Thus, at pH 4 almost none of the ascorbic acid permeated through the skin while at pH 6 relatively high skin permeability was obtained. The ascorbic acid loaded in the hydrogel particles was hardly degraded and its stability was maintained at high temperature.

Computational insights into the molecular interactions of environmental xenoestrogens 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and BPA metabolite, 4-methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene (MBP) with human sex hormone-binding globulin.

PubMed

Sheikh, Ishfaq A; Tayubi, Iftikhar A; Ahmad, Ejaz; Ganaie, Majid A; Bajouh, Osama S; AlBasri, Samera F; Abdulkarim, Ibtihal M J; Beg, Mohd A

2017-01-01

Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function. Copyright © 2016 Elsevier Inc. All rights reserved.

Acetic acid induces Sch9p-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria.

PubMed

Rego, António; Cooper, Katrina F; Snider, Justin; Hannun, Yusuf A; Costa, Vítor; Côrte-Real, Manuela; Chaves, Susana R

2018-06-01

Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1∆ mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 deletion leads to a higher retention of Isc1p in the endoplasmic reticulum upon acetic acid exposure. We also found that the higher resistance of all mutants correlates with higher levels of endogenous mitochondrial phosphorylated long chain bases (LCBPs), suggesting that changing the sphingolipid balance in favour of LCBPs in mitochondria results in increased survival to acetic acid. In conclusion, our results suggest that Sch9p pathways modulate acetic acid-induced cell death, through the regulation of Isc1p cellular distribution, thus affecting the sphingolipid balance that regulates cell fate. Copyright © 2018 Elsevier B.V. All rights reserved.

Neutralizing salivary pH by mouthwashes after an acidic challenge.

PubMed

Dehghan, Mojdeh; Tantbirojn, Daranee; Kymer-Davis, Emily; Stewart, Colette W; Zhang, Yanhui H; Versluis, Antheunis; Garcia-Godoy, Franklin

2017-05-01

The aim of the present study was to test the neutralizing effect of mouthwashes on salivary pH after an acidic challenge. Twelve participants were recruited for three visits, one morning per week. Resting saliva was collected at baseline and after 2-min swishing with 20 mL orange juice as an acidic challenge. Participants then rinsed their mouth for 30 s with 20 mL water (control), an over-the-counter mouthwash (Listerine), or a two-step mouthwash, randomly assigned for each visit. Saliva was collected immediately, 15, and 45 min after rinsing. The pH values of the collected saliva were measured and analyzed with anova, followed by Student-Newman-Keuls post-hoc test (significance level: 0.05). Orange juice significantly lowered salivary pH. Immediately after rinsing, Listerine and water brought pH back to baseline values, with the pH significantly higher in the Listerine group. The two-step mouthwash raised pH significantly higher than Listerine and water, and higher than the baseline value. Salivary pH returned to baseline and was not significantly different among groups at 15 and 45 min post-rinsing. Mouth rinsing after an acidic challenge increased salivary pH. The tested mouthwashes raised pH higher than water. Mouthwashes with a neutralizing effect can potentially reduce tooth erosion from acid exposure. © 2015 Wiley Publishing Asia Pty Ltd.

Intracellular pH regulation by acid-base transporters in mammalian neurons

PubMed Central

Ruffin, Vernon A.; Salameh, Ahlam I.; Boron, Walter F.; Parker, Mark D.

2014-01-01

Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions. PMID:24592239

Adsorption of 4-n-Nonylphenol and Bisphenol-A on Magnetic Reduced Graphene Oxides: A Combined Experimental and Theoretical Studies.

PubMed

Jin, Zhongxiu; Wang, Xiangxue; Sun, Yubing; Ai, Yuejie; Wang, Xiangke

2015-08-04

Adsorption of 4-n-nonylphenol (4-n-NP) and bisphenol A (BPA) on magnetic reduced graphene oxides (rGOs) as a function of contact time, pH, ionic strength and humic acid were investigated by batch techniques. Adsorption of 4-n-NP and BPA were independent of pH at 3.0- 8.0, whereas the slightly decreased adsorption was observed at pH 8.0-11.0. Adsorption kinetics and isotherms of 4-n-NP and BPA on magnetic rGOs can be satisfactorily fitted by pseudo-second-order kinetic and Freundlich model, respectively. The maximum adsorption capacities of magnetic rGOs at pH 6.5 and 293 K were 63.96 and 48.74 mg/g for 4-n-NP and BPA, respectively, which were significantly higher than that of activated carbon. Based on theoretical calculations, the higher adsorption energy of rGOs + 4-n-NP was mainly due to π-π stacking and flexible long alkyl chain of 4-n-NP, whereas adsorption of BPA on rGOs was energetically favored by a lying-down configuration due to π-π stacking and dispersion forces, which was further demonstrated by FTIR analysis. These findings indicate that magnetic rGOs is a promising adsorbent for the efficient elimination of 4-n-NP/BPA from aqueous solutions due to its excellent adsorption performance and simple magnetic separation, which are of great significance for the remediation of endocrine-disrupting chemicals in environmental cleanup.

Acidic Extracellular pH Promotes Activation of Integrin αvβ3

PubMed Central

Paradise, Ranjani K.; Lauffenburger, Douglas A.; Van Vliet, Krystyn J.

2011-01-01

Acidic extracellular pH is characteristic of the cell microenvironment in several important physiological and pathological contexts. Although it is well established that acidic extracellular pH can have profound effects on processes such as cell adhesion and migration, the underlying molecular mechanisms are largely unknown. Integrin receptors physically connect cells to the extracellular matrix, and are thus likely to modulate cell responses to extracellular conditions. Here, we examine the role of acidic extracellular pH in regulating activation of integrin αvβ3. Through computational molecular dynamics simulations, we find that acidic extracellular pH promotes opening of the αvβ3 headpiece, indicating that acidic pH can thereby facilitate integrin activation. This prediction is consistent with our flow cytometry and atomic force microscope-mediated force spectroscopy assays of integrin αvβ3 on live cells, which both demonstrate that acidic pH promotes activation at the intact cell surface. Finally, quantification of cell morphology and migration measurements shows that acidic extracellular pH affects cell behavior in a manner that is consistent with increased integrin activation. Taken together, these computational and experimental results suggest a new and complementary mechanism of integrin activation regulation, with associated implications for cell adhesion and migration in regions of altered pH that are relevant to wound healing and cancer. PMID:21283814

Effects of BPA and E2 on expression profiles of genes related to hypothalamic-pituitary-gonadal axis of half-smooth tongue sole Cynoglossus semilaevis

NASA Astrophysics Data System (ADS)

Li, Fengling; Li, Zhaoxin; Wang, Qingyin; Zhai, Yuxiu

2013-05-01

Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes ( DMRT, VTG GnRHR FSHR CYP17A CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations of Bisphenol A (BPA) and 17β-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects of E2 as a model estrogen were stronger. Among the 7 genes, VTG CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.

Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

PubMed

Valentino, L A; Holme, P A

2015-11-01

Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings. © 2015 John Wiley & Sons Ltd.

Isoelectric focusing of dansylated amino acids in immobilized pH gradients

NASA Technical Reports Server (NTRS)

Bianchi-Bosisio, Adriana; Righetti, Pier Giorgio; Egen, Ned B.; Bier, Milan

1986-01-01

The 21 free amino acids commonly encountered in proteins have been transformed into 'carrier ampholyte' species by reacting their primary amino groups with dansyl chloride. These derivatives can thus be focused in an immobilized pH gradient covering the pH interval 3.1 to 4.1, except for arginine, which still retains a pI of 8.8. Due to their inherent fluorescence, the dansyl derivatives are revealed in UV light, with a sensitivity of the order of 2-4 ng/sq mm. All nearest neighbors are separated except for the following couples: Asn-Gln, Gly-Thr, Val-Ile and Cys-Cys2, with a resolving power, in a Delta(pI) scale, of the order of 0.0018 pH units. Except for a few cases (notably the aromatic amino acids), the order of pI values is well correlated with the pK values of carboxyl groups, suggesting that the latter are not altered by dansylation. From the set of pK(COOH)-pI values of the different amino acids, the pK of the tertiary amino group in the dansyl label has been calculated to be 5.11 + or - 0.06. Knowing the pK of the amino-dansyl and the pI of the excess, free dansyl label (pI = 3.34), a pK of 1.57 is derived for its sulfonic acid group.

Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation

PubMed Central

Jagielska, Anna; Wilhite, Kristen D.; Van Vliet, Krystyn J.

2013-01-01

Axon remyelination in the central nervous system requires oligodendrocytes that produce myelin. Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. Here, we show that acidic extracellular pH, which is characteristic of demyelinating lesions, decreases the migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs), and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit directional migration along pH gradients toward acidic pH. These in vitro findings support a possible in vivo scenario whereby pH gradients attract OPCs toward acidic lesions, but resulting reduction in OPC survival and motility in acid decreases progress toward demyelinated axons and is further compounded by decreased differentiation into myelin-producing oligodendrocytes. As these processes are integral to OPC response to nerve demyelination, our results suggest that lesion acidity could contribute to decreased remyelination. PMID:24098762

Metabolic effects of p-coumaric acid in the perfused rat liver.

PubMed

Lima, Leonardo C N; Buss, Gisele D; Ishii-Iwamoto, Emy L; Salgueiro-Pagadigorria, Clairce; Comar, Jurandir Fernando; Bracht, Adelar; Constantin, Jorgete

2006-01-01

The p-coumaric acid, a phenolic acid, occurs in several plant species and, consequently, in many foods and beverages of vegetable origin. Its antioxidant activity is well documented, but there is also a single report about an inhibitory action on the monocarboxylate carrier, which operates in the plasma and mitochondrial membranes. The latter observation suggests that p-coumaric acid could be able to inhibit gluconeogenesis and related parameters. The present investigation was planned to test this hypothesis in the isolated and hemoglobin-free perfused rat liver. Transformation of lactate and alanine into glucose (gluconeogenesis) in the liver was inhibited by p-coumaric acid (IC50 values of 92.5 and 75.6 microM, respectively). Transformation of fructose into glucose was inhibited to a considerably lower degree (maximally 28%). The oxygen uptake increase accompanying gluconeogenesis from lactate was also inhibited. Pyruvate carboxylation in isolated intact mitochondria was inhibited (IC50 = 160.1 microM); no such effect was observed in freeze-thawing disrupted mitochondria. Glucose 6-phosphatase and fructose 1,6-bisphosphatase were not inhibited. In isolated intact mitochondria, p-coumaric acid inhibited respiration dependent on pyruvate oxidation but was ineffective on respiration driven by succinate and beta-hydroxybutyrate. It can be concluded that inhibition of pyruvate transport into the mitochondria is the most prominent primary effect of p-coumaric acid and also the main cause for gluconeogenesis inhibition. The existence of additional actions of p-coumaric acid, such as enzyme inhibitions and interference with regulatory mechanisms, cannot be excluded. 2006 Wiley Periodicals, Inc.

A novel acidic pH fluorescent probe based on a benzothiazole derivative

NASA Astrophysics Data System (ADS)

Ma, Qiujuan; Li, Xian; Feng, Suxiang; Liang, Beibei; Zhou, Tiqiang; Xu, Min; Ma, Zhuoyi

2017-04-01

A novel acidic pH fluorescent probe 1 based on a benzothiazole derivative has been designed, synthesized and developed. The linear response range covers the acidic pH range from 3.44 to 6.46, which is valuable for pH researches in acidic environment. The evaluated pKa value of the probe 1 is 4.23. The fluorescence enhancement of the studied probe 1 with an increase in hydrogen ions concentration is based on the hindering of enhanced photo-induced electron transfer (PET) process. Moreover, the pH sensor possesses a highly selective response to H+ in the presence of metal ions, anions and other bioactive small molecules which would be interfere with its fluorescent pH response. Furthermore, the probe 1 responds to acidic pH with short response time that was less than 1 min. The probe 1 has been successfully applied to confocal fluorescence imaging in live HeLa cells and can selectively stain lysosomes. All of such good properties prove it can be used to monitoring pH fluctuations in acidic environment with high sensitivity, pH dependence and short response time.

Crystallization of recombinant Haemophilus influenzaee (P4) acid phosphatase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, Zhonghui; Felts, Richard L.; Reilly, Thomas J.

2006-05-01

Lipoprotein e (P4) is a class C acid phosphatase and a potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. Haemophilus influenzae infects the upper respiratory tract of humans and can cause infections of the middle ear, sinuses and bronchi. The virulence of the pathogen is thought to involve a group of surface-localized macromolecular components that mediate interactions at the host–pathogen interface. One of these components is lipoprotein e (P4), which is a class C acid phosphatase and amore » potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. The space group is P4{sub 2}2{sub 1}2, with unit-cell parameters a = 65.6, c = 101.4 Å, one protein molecule per asymmetric unit and 37% solvent content. This is the first report of the crystallization of a class C acid phosphatase.« less

40 CFR 721.10370 - Phosphonic acid, p-octyl-, lanthanum (3+) salt (2:1).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, p-octyl-, lanthanum... New Uses for Specific Chemical Substances § 721.10370 Phosphonic acid, p-octyl-, lanthanum (3+) salt... substance identified as phosphinic acid, p-octyl-, lanthanum (3+) salt (2:1) (PMN P-10-99; CAS No. 1186211...

40 CFR 721.10370 - Phosphonic acid, p-octyl-, lanthanum (3+) salt (2:1).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, p-octyl-, lanthanum... New Uses for Specific Chemical Substances § 721.10370 Phosphonic acid, p-octyl-, lanthanum (3+) salt... substance identified as phosphinic acid, p-octyl-, lanthanum (3+) salt (2:1) (PMN P-10-99; CAS No. 1186211...

40 CFR 721.10370 - Phosphonic acid, p-octyl-, lanthanum (3+) salt (2:1).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, p-octyl-, lanthanum... New Uses for Specific Chemical Substances § 721.10370 Phosphonic acid, p-octyl-, lanthanum (3+) salt... substance identified as phosphinic acid, p-octyl-, lanthanum (3+) salt (2:1) (PMN P-10-99; CAS No. 1186211...

p21 induction plays a dual role in anti-cancer activity of ursolic acid

PubMed Central

Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong

2015-01-01

Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

PubMed Central

Guven, Mustafa; Aras, Adem Bozkurt; Akman, Tarik; Sen, Halil Murat; Ozkan, Adile; Salis, Osman; Sehitoglu, Ibrahim; Kalkan, Yildiray; Silan, Coskun; Deniz, Mustafa; Cosar, Murat

2015-01-01

Objective(s): Stroke poses a crucial risk for mortality and morbidity. Our study aimed to investigate the effect of p-coumaric acid on focal cerebral ischemia in rats. Material and Methods: Rats were randomly divided into four groups, namely Group I (control rats), Group II (ischemia rats), Group III (6 hr ischemia + p-coumaric acid rats) and Group IV (24 hr ischemia + p-coumaric acid rats). Cerebral ischemia was induced via intraluminal monofilament occlusion model. In all groups, the brain was removed after the procedure and rats were sacrificed. Malondialdehyde, superoxide dismutase and nuclear respiratory factor-1 were measured in the ischemic hemisphere. The histopathological changes were observed in the right hemisphere within the samples. Functional assessment was performed for neurological deficit scores. Results: Following the treatment, biochemical factors changed significantly. Histopathologically, it was shown that p-coumaric acid decreased the oxidative damage. The neurological deficit scores of p-coumaric acid-treated rats were significantly improved after cerebral ischemia. Conclusion: Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future. PMID:26019798

A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

PubMed Central

Moreno, Ricardo D.

2014-01-01

Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

Poly(aspartic acid) with adjustable pH-dependent solubility.

PubMed

Németh, Csaba; Gyarmati, Benjámin; Abdullin, Timur; László, Krisztina; Szilágyi, András

2017-02-01

Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pK a . Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings. Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pK a values of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract

The effectiveness of the high-LET radiations from the boron neutron capture [10B(n,α) 7Li] reaction determined for induction of chromosome aberrations and apoptosis in lymphocytes of human blood samples.

PubMed

Schmid, T E; Canella, L; Kudejova, P; Wagner, F M; Röhrmoser, A; Schmid, E

2015-03-01

Provided that a selective accumulation of (10)B-containing compounds is introduced in tumor cells, following irradiation by thermal neutrons produces high-LET alpha-particles ((4)He) and recoiling lithium-7 ((7)Li) nuclei emitted during the capture of thermalized neutrons (0.025 eV) from (10)B. To estimate the biological effectiveness of this boron neutron capture [(10)B(n,α)(7)Li] reaction, the chromosome aberration assay and the flow cytometry apoptosis assay were applied. At the presence of the clinically used compounds BSH (sodium borocaptate) and BPA (p-boronophenylalanine), human lymphocytes were irradiated by sub-thermal neutrons. For analyzing chromosome aberrations, human lymphocytes were exposed to thermally equivalent neutron fluences of 1.82 × 10(11) cm(-2) or 7.30 × 10(11) cm(-2) (corresponding to thermal neutron doses of 0.062 and 0.248 Gy, respectively) in the presence of 0, 10, 20, and 30 ppm of BSH or BPA. Since the kerma coefficient of blood increased by 0.864 × 10(-12) Gy cm(2) per 10 ppm of (10)B, the kerma coefficients in blood increase from 0.34 × 10(-12) cm(2) (blood without BSH or BPA) up to 2.93 × 10(-12) Gy cm(2) in the presence of 30 ppm of (10)B. For the (10)B(n, α)(7)Li reaction, linear dose-response relations for dicentrics with coefficients α = 0.0546 ± 0.0081 Gy(-1) for BSH and α = 0.0654 ± 0.0075 Gy(-1) for BPA were obtained at 0.062 Gy as well as α = 0.0985 ± 0.0284 Gy(-1) for BSH and α = 0.1293 ± 0.0419 Gy(-1) for BPA at 0.248 Gy. At both doses, the corresponding (10)B(n, α)(7)Li reactions from BSH and BPA are not significantly different. A linear dose-response relation for dicentrics also was obtained for the induction of apoptosis by the (10)B(n, α)(7)Li reaction at 0.248 Gy. The linear coefficients α = 0.0249 ± 0.0119 Gy(-1) for BSH and α = 0.0334 ± 0.0064 Gy(-1) for BPA are not significantly different. Independently of the applied thermal neutron doses of

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity.

PubMed

Vauzour, David; Corona, Giulia; Spencer, Jeremy P E

2010-09-01

Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids. Copyright © 2010. Published by Elsevier Inc.

Nestedness in Arbuscular Mycorrhizal Fungal Communities along Soil pH Gradients in Early Primary Succession: Acid-Tolerant Fungi Are pH Generalists

PubMed Central

Kawahara, Ai; An, Gi-Hong; Miyakawa, Sachie; Sonoda, Jun

2016-01-01

Soil acidity is a major constraint on plant productivity. Arbuscular mycorrhizal (AM) fungi support plant colonization in acidic soil, but soil acidity also constrains fungal growth and diversity. Fungi in extreme environments generally evolve towards specialists, suggesting that AM fungi in acidic soil are acidic-soil specialists. In our previous surveys, however, some AM fungi detected in strongly acidic soils could also be detected in a soil with moderate pH, which raised a hypothesis that the fungi in acidic soils are pH generalists. To test the hypothesis, we conducted a pH-manipulation experiment and also analyzed AM fungal distribution along a pH gradient in the field using a synthesized dataset of the previous and recent surveys. Rhizosphere soils of the generalist plant Miscanthus sinensis were collected both from a neutral soil and an acidic soil, and M. sinensis seedlings were grown at three different pH. For the analysis of field communities, rhizosphere soils of M. sinensis were collected from six field sites across Japan, which covered a soil pH range of 3.0–7.4, and subjected to soil trap culture. AM fungal community compositions were determined based on LSU rDNA sequences. In the pH-manipulation experiment the acidification of medium had a significant impact on the compositions of the community from the neutral soil, but the neutralization of the medium had no effect on those of the community from the acidic soil. Furthermore, the communities in lower -pH soils were subsets of (nested in) those in higher-pH soils. In the field communities a significant nestedness pattern was observed along the pH gradient. These observations suggest that the fungi in strongly acidic soils are pH generalists that occur not only in acidic soil but also in wide ranges of soil pH. Nestedness in AM fungal community along pH gradients may have important implications for plant community resilience and early primary succession after disturbance in acidic soils. PMID

Nestedness in Arbuscular Mycorrhizal Fungal Communities along Soil pH Gradients in Early Primary Succession: Acid-Tolerant Fungi Are pH Generalists.

PubMed

Kawahara, Ai; An, Gi-Hong; Miyakawa, Sachie; Sonoda, Jun; Ezawa, Tatsuhiro

2016-01-01

Soil acidity is a major constraint on plant productivity. Arbuscular mycorrhizal (AM) fungi support plant colonization in acidic soil, but soil acidity also constrains fungal growth and diversity. Fungi in extreme environments generally evolve towards specialists, suggesting that AM fungi in acidic soil are acidic-soil specialists. In our previous surveys, however, some AM fungi detected in strongly acidic soils could also be detected in a soil with moderate pH, which raised a hypothesis that the fungi in acidic soils are pH generalists. To test the hypothesis, we conducted a pH-manipulation experiment and also analyzed AM fungal distribution along a pH gradient in the field using a synthesized dataset of the previous and recent surveys. Rhizosphere soils of the generalist plant Miscanthus sinensis were collected both from a neutral soil and an acidic soil, and M. sinensis seedlings were grown at three different pH. For the analysis of field communities, rhizosphere soils of M. sinensis were collected from six field sites across Japan, which covered a soil pH range of 3.0-7.4, and subjected to soil trap culture. AM fungal community compositions were determined based on LSU rDNA sequences. In the pH-manipulation experiment the acidification of medium had a significant impact on the compositions of the community from the neutral soil, but the neutralization of the medium had no effect on those of the community from the acidic soil. Furthermore, the communities in lower -pH soils were subsets of (nested in) those in higher-pH soils. In the field communities a significant nestedness pattern was observed along the pH gradient. These observations suggest that the fungi in strongly acidic soils are pH generalists that occur not only in acidic soil but also in wide ranges of soil pH. Nestedness in AM fungal community along pH gradients may have important implications for plant community resilience and early primary succession after disturbance in acidic soils.

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphinic acid, P,P-diethyl-, zinc salt (2:1). 721.10135 Section 721.10135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10135...

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphinic acid, P,P-diethyl-, zinc salt (2:1). 721.10135 Section 721.10135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10135...

40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphinic acid, P,P-diethyl-, zinc salt (2:1). 721.10135 Section 721.10135 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10135...

Physiological analysis of the effects of rikkunshito on acid and non-acid gastroesophageal reflux using pH-multichannel intraluminal impedance monitoring.

PubMed

Kawahara, Hisayoshi; Tazuke, Yuko; Soh, Hideki; Yoneda, Akihiro; Fukuzawa, Masahiro

2014-09-01

To clarify the effects of rikkunshito on acid reflux, non-acid reflux, and esophageal clearance in patients with gastroesophageal reflux disease (GERD). We enrolled seven patients with vomiting and/or stridor (median 6 years; 1 month-17 years), with a percent total time of esophageal pH <4.0 (reflux index) over 4.0%. Rikkunshito (TJ-43; Tsumura Co, Tokyo, Japan) was given in three divided doses before meals. We retrospectively investigated its efficacy using pH-multichannel intraluminal impedance before and 7 (6-10) days after starting treatment. Statistical analyses were conducted using Wilcoxon signed-rank test. In the pH analyses alone, the median number of acid reflux episodes >5 min (14 versus 10, p = 0.046) and median acid-clearance time (184 versus 134 s, p = 0.03) decreased significantly, although median decrease in reflux index did not reach significance (16.0 versus 17.9%, p = 0.06). In the combined impedance and pH analyses, the median number (36 versus 36, p = 0.03) and median duration (1.9 versus 1.1%, p = 0.046) of acid reflux decreased significantly; non-acid reflux and bolus clearance time did not change. Rikkunshito effectively reduced acid reflux, but not esophageal clearance, in patients with GERD.

Proline/pipecolinic acid-promoted copper-catalyzed P-arylation.

PubMed

Huang, Cheng; Tang, Xu; Fu, Hua; Jiang, Yuyang; Zhao, Yufen

2006-06-23

We have developed a convenient and efficient approach for P-arylation of organophosphorus compounds containing P-H. Using commercially available and inexpensive proline and pipecolinic acid as the ligands greatly improved the efficiency of the coupling reactions, so the method can provide an entry to arylphosphonates, arylphosphinates and arylphosphine oxides.

Putting the pH into phosphatidic acid signaling

PubMed Central

2011-01-01

The lipid phosphatidic acid (PA) has important roles in cell signaling and metabolic regulation in all organisms. New evidence indicates that PA also has an unprecedented role as a pH biosensor, coupling changes in pH to intracellular signaling pathways. pH sensing is a property of the phosphomonoester headgroup of PA. A number of other potent signaling lipids also contain headgroups with phosphomonoesters, implying that pH sensing by lipids may be widespread in biology. PMID:22136116

Global Survey of Submicron Aerosol Acidity (pH)

NASA Astrophysics Data System (ADS)

Nault, B.; Day, D. A.; Campuzano Jost, P.; Hu, W.; Schroder, J. C.; Bian, H.; Chin, M.; Clegg, S. L.; Colarco, P. R.; Dibb, J. E.; Kim, M. J.; Kodros, J.; Marais, E. A.; Pierce, J. R.; Scheuer, E. M.; Wennberg, P. O.; Jimenez, J. L.

2017-12-01

Aerosol acidity (H+, often expressed as "pH" defined in various ways) is an important property that influences uptake and partitioning of gases, and homogeneous and surface aqueous reactions of key inorganic and organic compounds. As there is currently no rapid method to measure ambient aerosol acidity, a thermodynamic model, constrained by both inorganic aerosol species (e.g., NH4, NO3, SO4, Cl) and at least one inorganic gas (HNO3, NH3, or HCl), are currently understood to lead to the most reliable estimates of aerosol acidity. In this study, we calculated submicron (less than PM1) aerosol pH from the NASA ATom, "pole-to-pole," flights that covers both the Pacific and Atlantic ocean basins. The E-AIM thermodynamic model was used with measurements by an Aerodyne high-resolution time-of-flight aerosol-mass-spectrometer (HR-ToF-AMS) of inorganic aerosol species, along with inorganic gas measurements from other mass spectrometers and ion chromatography. We compare the results with those for the NASA KORUS-AQ, SEAC4RS, DC3, and ARCTAS campaigns, as well as several ground-based campaigns and recently-published studies. This provides an opportunity to compare the aerosol acidity in urban, rural, and remote regions, by season, and between the boundary layer and free troposphere. In addition, we compare the submicron aerosol acidity from these various localities with results from global models, such as GEOS-Chem, in order to investigate the ability of the global models to simulate aerosol acidity, and the processes it affects, such as nitrate, ammonium, and MSA partitioning.

Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs

PubMed Central

Liu, Hong; Wang, Jun; Mou, Daolin; Che, Lianqiang; Fang, Zhengfeng; Feng, Bin; Lin, Yan; Xu, Shengyu; Li, Jian; Wu, De

2017-01-01

This study was conducted to explore whether exposure to bisphenol A (BPA) during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET) could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON); control diet supplemented with BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with BPA and MET supplementation (BPA + MET). Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation. PMID

Biodegradation of toxic chemicals by Pleurotus eryngii in submerged fermentation and solid-state fermentation.

PubMed

Chang, Bea-Ven; Chang, Yi-Ming

2016-04-01

The toxic chemicals bisphenol A (BPA), bisphenol F (BPF), nonylphenol (NP), and tetrabromobisphenol A (TBBPA) are endocrine-disrupting chemicals that have consequently drawn much concern regarding their effect on the environment. The objectives of this study were to investigate the degradation of BPA, BPF, NP, and TBBPA by enzymes from Pleurotus eryngii in submerged fermentation (SmF) and solid-state fermentation (SSF), and also to assess the removal of toxic chemicals in spent mushroom compost (SMC). BPA and BPF were analyzed by high-performance liquid chromatography; NP and TBBPA were analyzed by gas chromatography. NP degradation was enhanced by adding CuSO4 (1 mM), MnSO4 (0.5 mM), gallic acid (1 mM), tartaric acid (20 mM), citric acid (20 mM), guaiacol (1 mM), or 2,2'-azino-bis- (3-ethylbenzothiazoline-6-sulfonic acid; 1 mM), with the last yielding a higher NP degradation rate than the other additives from SmF. The optimal conditions for enzyme activity from SSF were a sawdust/wheat bran ratio of 1:4 and a moisture content of 5 mL/g. The enzyme activities were higher with sawdust/wheat bran than with sawdust/rice bran. The optimal conditions for the extraction of enzyme from SMC required using sodium acetate buffer (pH 5.0, solid/solution ratio 1:5), and extraction over 3 hours. The removal rates of toxic chemicals by P. eryngii, in descending order of magnitude, were SSF > SmF > SMC. The removal rates were BPF > BPA > NP > TBBPA. Copyright © 2014. Published by Elsevier B.V.

Adsorption characteristics of Bisphenol-A on tailored activated carbon in aqueous solutions.

PubMed

Yan, Liang; Lv, Di; Huang, Xinwen; Shi, Huixiang; Zhang, Geshan

2016-10-01

The adsorption behavior of pharmaceuticals and personal care product, Bisphenol-A (BPA), according to four coal-based and four wood-based granular activated carbons modified using outgassing treatment, acidic treatment or alkaline treatment was studied. The adsorption isotherm results indicated that carbon surface acidity played a very important role in the adsorption of BPA. It was found that increasing surface acidity would increase the hydrogen bonding effects and increase adsorption of BPA on activated carbon. The acidic modified sample (F600-A and OLC-A) represented the best adsorption capacity, and the equilibrium adsorption amounts reached 346.42 and 338.55 mg/g, respectively. Further, effects of surface charge and surface basicity were examined. It was found that the adsorbed amount of BPA decreased with the increase of surface charge. Finally, there appeared to be a significant oligomerization phenomenon with BPA molecules onto the surface of activated carbon. OLC and OLC-OG, which have higher micropore percentages, are very effective in hampering the oligomerization of BPA under oxic conditions.

Differential Effects of Methoxylated p-Coumaric Acids on Melanoma in B16/F10 Cells

PubMed Central

Yoon, Hoon Seok; Lee, Nam-Ho; Hyun, Chang-Gu; Shin, Dong-Bum

2015-01-01

As an approach to search for chemopreventive agents, we tested p-coumaric acid, 3-methoxy-p-coumaric acid (ferulic acid), and 3,5-dimethoxy-p-coumaric acid (sinapic acid) in B16/F10 melanoma cells. Intracellular melanin contents were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cytotoxicity of the compounds were examined by lactate dehydrogenase (LDH) release. p-Coumaric acid showed inhibitory effect on melanogenesis, but ferulic acid increased melanin content, and sinapic acid had almost no effect on melanogenesis. Treatment with ferulic acid resulted in a 2 to 3 fold elevation in the production of melanin. Correlatively, cell viability decreased in a dose-dependent manner when treated with ferulic acid. However, ferulic acid did not affect the LDH release from the cells. Treatment with sinapic acid resulted in a 50~60% elevation in the release of LDH when treated with a 200 μg/mL concentration and showed neither cytostasis nor increase of melanin synthesis in a dose-dependent manner. Taken together, p-coumaric acid inhibits melanogenesis, ferulic acid induces melanogenesis, and sinapic acid exerts cytotoxic effects in B16/F10 murine melanoma cells. The results indicate that the addition of methoxy groups to p-coumaric acid shows the melanogenic or cytotoxic effects in melanoma cells compared to the original compound. Therefore, this study suggests the possibility that methoxylated p-coumaric acid, ferulic acid can be used as a chemopreventive agent. PMID:25866753

Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?

PubMed Central

2012-01-01

Background The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO2 producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing proposal that life arose within alkaline (pH 9-11) deep-sea hydrothermal vents like those of the 'Lost City', with the interface with the acidic ocean creating a proton gradient sufficient to drive the first metabolism. However, RNA is most stable at pH 4-5 and is unstable at alkaline pH, raising the possibility that RNA may have first arisen in the acidic ocean itself (possibly near an acidic hydrothermal vent), acidic volcanic lake or comet pond. As the Hadean Eon progressed, the ocean pH is inferred to have gradually risen to near neutral as atmospheric CO2 levels decreased. Presentation of the hypothesis We propose that RNA is well suited for a world evolving at acidic pH. This is supported by the enhanced stability at acidic pH of not only the RNA phosphodiester bond but also of the aminoacyl-(t)RNA and peptide bonds. Examples of in vitro-selected ribozymes with activities at acid pH have recently been documented. The subsequent transition to a DNA genome could have been partly driven by the gradual rise in ocean pH, since DNA has greater stability than RNA at alkaline pH, but not at acidic pH. Testing the hypothesis We have proposed mechanisms for two key RNA world activities that are compatible with an acidic milieu: (i) non-enzymatic RNA replication of a hemi-protonated cytosine-rich oligonucleotide, and (ii) specific aminoacylation of tRNA/hairpins through triple helix interactions between the helical aminoacyl stem and a single-stranded aminoacylating ribozyme. Implications of the hypothesis Our hypothesis casts doubt on the hypothesis that RNA evolved in the vicinity of alkaline hydrothermal vents. The

pH at the micellar interface: synthesis of pH probes derived from salicylic acid, acid-base dissociation in sodium dodecyl sulfate micelles, and Poisson-Boltzmann simulation.

PubMed

Souza, T P; Zanette, D; Kawanami, A E; de Rezende, L; Ishiki, H M; do Amaral, A T; Chaimovich, H; Agostinho-Neto, A; Cuccovia, I M

2006-05-01

The study of the H+ concentration at the micellar interface is a convenient system for modeling the distribution of H+ at interfaces. We have synthesized salicylic acid derivatives to analyze the proton dissociation of both the carboxylic and phenol groups of the probes, determining spectrophotometrically the apparent pK(a)'s (pK(ap)) in sodium dodecyl sulfate, SDS, micelles with and without added salt. The synthesized probes were 2-hydroxy-5-(2-trimethylammoniumacetyl)benzoate; 2-hydroxy-5-(2-dimethylhexadecylammoniumacetyl)benzoate; 2-hydroxy-5-(2-dimethylhexadecylammoniumhexanoyl)benzoate; 2-hydroxy-5-(2-dimethylhexadecylammoniumundecanoyl)benzoate; 2-hydroxy-5-acetylbenzoic acid; and 2-hydroxy-5-dodecanoylbenzoic acid. Upon incorporation into SDS micelles the pK(ap)'s of both carboxylic and phenol groups increased by ca. 3 pH units and NaCl addition caused a decrease in the probe-incorporated pK(ap). The experimental results were fitted with a cell model Poisson-Boltzmann (P-B) equation taking in consideration the effect of salt on the aggregation number of SDS and using the distance of the dissociating group as a parameter. The conformations of the probes were analyzed theoretically using two dielectric constants, e.g., 2 and 78. Both the P-B analysis and conformation calculations can be interpreted by assuming that the acid groups dissociate very close to, or at, the interface. Our results are consistent with the assumption that the intrinsic pK(a)'s of both carboxylic and phenol groups of the salicylic acid probes used here can be taken as those in water. Using this assumption the micellar and salt effects on the pK(ap)'s of the (trialkylammonium)benzoate probes were described accurately using a cell model P-B analysis.

Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.

PubMed

Choi, Jeongjoon; Groisman, Eduardo A

2016-09-01

pH regulates gene expression, biochemical activities and cellular behaviors. A mildly acidic pH activates the master virulence regulatory system PhoP/PhoQ in the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The sensor PhoQ harbors an extracytoplasmic domain implicated in signal sensing, and a cytoplasmic domain controlling activation of the regulator PhoP. We now report that, surprisingly, a decrease in Salmonella's own cytoplasmic pH induces transcription of PhoP-activated genes even when the extracytoplasmic pH remains neutral. Amino acid substitutions in PhoQ's cytoplasmic domain hindered activation by acidic pH and attenuated virulence in mice, but did not abolish activation by low Mg(2+) or the antimicrobial peptide C18G. Conversely, removal of PhoQ's extracytoplasmic domains prevented the response to the latter PhoQ-activating signals but not to acidic pH. PhoP-dependent genes were minimally induced by acidic pH in the non-pathogenic species Salmonella bongori but were activated by low Mg(2+) and C18G as in pathogenic S. enterica. Our findings indicate that the sensor PhoQ enables S. enterica to respond to both host- and bacterial-derived signals that alter its cytoplasmic pH. © 2016 John Wiley & Sons Ltd.

p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities.

PubMed

Pei, Kehan; Ou, Juanying; Huang, Junqing; Ou, Shiyi

2016-07-01

p-Coumaric acid (4-hydroxycinnamic acid) is a phenolic acid that has low toxicity in mice (LD50 = 2850 mg kg(-1) body weight), serves as a precursor of other phenolic compounds, and exists either in free or conjugated form in plants. Conjugates of p-coumaric acid have been extensively studied in recent years due to their bioactivities. In this review, the occurrence, bioavailability and bioaccessibility of p-coumaric acid and its conjugates with mono-, oligo- and polysaccharides, alkyl alcohols, organic acids, amine and lignin are discussed. Their biological activities, including antioxidant, anti-cancer, antimicrobial, antivirus, anti-inflammatory, antiplatelet aggregation, anxiolytic, antipyretic, analgesic, and anti-arthritis activities, and their mitigatory effects against diabetes, obesity, hyperlipaemia and gout are compared. Cumulative evidence from multiple studies indicates that conjugation of p-coumaric acid greatly strengthens its biological activities; however, the high biological activity but low absorption of its conjugates remains a puzzle. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Average rainwater pH, concepts of atmospheric acidity, and buffering in open systems

NASA Astrophysics Data System (ADS)

Liljestrand, Howard M.

The system of water equilibrated with a constant partial pressure of CO 2, as a reference point for pH acidity-alkalinity relationships, has nonvolatile acidity and alkalinity components as conservative quantities, but not [H +]. Simple algorithms are presented for the determination of the average pH for combinations of samples both above and below pH 5.6. Averaging the nonconservative quantity [H +] yields erroneously low mean pH values. To extend the open CO 2 system to include other volatile atmospheric acids and bases distributed among the gas, liquid and particulate matter phases, a theoretical framework for atmospheric acidity is presented. Within certain oxidation-reduction limitations, the total atmospheric acidity (but not free acidity) is a conservative quantity. The concept of atmospheric acidity is applied to air-water systems approximating aerosols, fogwater, cloudwater and rainwater. The buffer intensity in hydrometeors is described as a function of net strong acidity, partial pressures of acid and base gases and the water to air ratio. For high liquid to air volume ratios, the equilibrium partial pressures of trace acid and base gases are set by the pH or net acidity controlled by the nonvolatile acid and base concentrations. For low water to air volume ratios as well as stationary state systems such as precipitation scavenging with continuous emissions, the partial pressures of trace gases (NH 3, HCl, HNO 3, SO 2 and CH 3COOH) appear to be of greater or equal importance as carbonate species as buffers in the aqueous phase.

Cu(II) binding by a pH-fractionated fulvic acid

USGS Publications Warehouse

Brown, G.K.; Cabaniss, S.E.; MacCarthy, P.; Leenheer, J.A.

1999-01-01

The relationship between acidity, Cu(II) binding and sorption to XAD resin was examined using Suwannee River fulvic acid (SRFA). The work was based on the hypothesis that fractions of SRFA eluted from an XAD column at various pH's from 1.0 to 12.0 would show systematic variations in acidity and possibly aromaticity which in turn would lead to different Cu(II) binding properties. We measured equilibrium Cu(II) binding to these fractions using Cu2+ ion-selective electrode (ISE) potentiometry at pH 6.0. Several model ligands were also examined, including cyclopentane-1,2,3,4-tetracarboxylic acid (CP-TCA) and tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THF-TCA), the latter binding Cu(II) much more strongly as a consequence of the ether linkage. The SRFA Cu(II) binding properties agreed with previous work at high ionic strength, and binding was enhanced substantially at lower ionic strength, in agreement with Poisson-Boltzmann predictions for small spheres. Determining Cu binding constants (K(i)) by non-linear regression with total ligand concentrations (L(Ti)) taken from previous work, the fractions eluted at varying pH had K(i) similar to the unfractionated SRFA, with a maximum enhancement of 0.50 log units. We conclude that variable-pH elution from XAD does not isolate significantly strong (or weak) Cu(II)-binding components from the SRFA mixture. Copyright (C) 1999 Elsevier Science B.V.

Estimates of Dietary Exposure to Bisphenol A (BPA) from Light Metal Packaging using Food Consumption and Packaging usage Data: A Refined Deterministic Approach and a Fully Probabilistic (FACET) Approach

PubMed Central

Oldring, P.K.T.; Castle, L.; O'Mahony, C.; Dixon, J.

2013-01-01

The FACET tool is a probabilistic model to estimate exposure to chemicals in foodstuffs, originating from flavours, additives and food contact materials. This paper demonstrates the use of the FACET tool to estimate exposure to BPA (bisphenol A) from light metal packaging. For exposure to migrants from food packaging, FACET uses industry-supplied data on the occurrence of substances in the packaging, their concentrations and construction of the packaging, which were combined with data from a market research organisation and food consumption data supplied by national database managers. To illustrate the principles, UK packaging data were used together with consumption data from the UK National Diet and Nutrition Survey (NDNS) dietary survey for 19–64 year olds for a refined deterministic verification. The UK data were chosen mainly because the consumption surveys are detailed, data for UK packaging at a detailed level were available and, arguably, the UK population is composed of high consumers of packaged foodstuffs. Exposures were run for each food category that could give rise to BPA from light metal packaging. Consumer loyalty to a particular type of packaging, commonly referred to as packaging loyalty, was set. The BPA extraction levels used for the 15 types of coating chemistries that could release BPA were in the range of 0.00005–0.012 mg dm−2. The estimates of exposure to BPA using FACET for the total diet were 0.0098 (mean) and 0.0466 (97.5th percentile) mg/person/day, corresponding to 0.00013 (mean) and 0.00059 (97.5th percentile) mg kg−1 body weight day−1 for consumers of foods packed in light metal packaging. This is well below the current EFSA (and other recognised bodies) TDI of 0.05 mg kg−1 body weight day. These probabilistic estimates were compared with estimates using a refined deterministic approach drawing on the same input data. The results from FACET for the mean, 95th and 97.5th percentile exposures to BPA lay between the lowest

Estimates of dietary exposure to bisphenol A (BPA) from light metal packaging using food consumption and packaging usage data: a refined deterministic approach and a fully probabilistic (FACET) approach.

PubMed

Oldring, P K T; Castle, L; O'Mahony, C; Dixon, J

2014-01-01

The FACET tool is a probabilistic model to estimate exposure to chemicals in foodstuffs, originating from flavours, additives and food contact materials. This paper demonstrates the use of the FACET tool to estimate exposure to BPA (bisphenol A) from light metal packaging. For exposure to migrants from food packaging, FACET uses industry-supplied data on the occurrence of substances in the packaging, their concentrations and construction of the packaging, which were combined with data from a market research organisation and food consumption data supplied by national database managers. To illustrate the principles, UK packaging data were used together with consumption data from the UK National Diet and Nutrition Survey (NDNS) dietary survey for 19-64 year olds for a refined deterministic verification. The UK data were chosen mainly because the consumption surveys are detailed, data for UK packaging at a detailed level were available and, arguably, the UK population is composed of high consumers of packaged foodstuffs. Exposures were run for each food category that could give rise to BPA from light metal packaging. Consumer loyalty to a particular type of packaging, commonly referred to as packaging loyalty, was set. The BPA extraction levels used for the 15 types of coating chemistries that could release BPA were in the range of 0.00005-0.012 mg dm(-2). The estimates of exposure to BPA using FACET for the total diet were 0.0098 (mean) and 0.0466 (97.5th percentile) mg/person/day, corresponding to 0.00013 (mean) and 0.00059 (97.5th percentile) mg kg(-1) body weight day(-1) for consumers of foods packed in light metal packaging. This is well below the current EFSA (and other recognised bodies) TDI of 0.05 mg kg(-1) body weight day(-1). These probabilistic estimates were compared with estimates using a refined deterministic approach drawing on the same input data. The results from FACET for the mean, 95th and 97.5th percentile exposures to BPA lay between the

Boron neutron capture therapy for recurrent high-grade meningiomas.

PubMed

Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Ono, Koji; Miyatake, Shin-Ichi

2013-10-01

Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.

Influence of sodium chloride, pH, and lactic acid bacteria on anaerobic lactic acid utilization during fermented cucumber spoilage.

PubMed

Johanningsmeier, Suzanne D; Franco, Wendy; Perez-Diaz, Ilenys; McFeeters, Roger F

2012-07-01

Cucumbers are preserved commercially by natural fermentations in 5% to 8% sodium chloride (NaCl) brines. Occasionally, fermented cucumbers spoil after the primary fermentation is complete. This spoilage has been characterized by decreases in lactic acid and a rise in brine pH caused by microbial instability. Objectives of this study were to determine the combined effects of NaCl and pH on fermented cucumber spoilage and to determine the ability of lactic acid bacteria (LAB) spoilage isolates to initiate lactic acid degradation in fermented cucumbers. Cucumbers fermented with 0%, 2%, 4%, and 6% NaCl were blended into slurries (FCS) and adjusted to pH 3.2, 3.8, 4.3, and 5.0 prior to centrifugation, sterile-filtration, and inoculation with spoilage organisms. Organic acids and pH were measured initially and after 3 wk, 2, 6, 12, and 18 mo anaerobic incubation at 25 °C. Anaerobic lactic acid degradation occurred in FCS at pH 3.8, 4.3, and 5.0 regardless of NaCl concentration. At pH 3.2, reduced NaCl concentrations resulted in increased susceptibility to spoilage, indicating that the pH limit for lactic acid utilization in reduced NaCl fermented cucumbers is 3.2 or lower. Over 18 mo incubation, only cucumbers fermented with 6% NaCl to pH 3.2 prevented anaerobic lactic acid degradation by spoilage bacteria. Among several LAB species isolated from fermented cucumber spoilage, Lactobacillus buchneri was unique in its ability to metabolize lactic acid in FCS with concurrent increases in acetic acid and 1,2-propanediol. Therefore, L. buchneri may be one of multiple organisms that contribute to development of fermented cucumber spoilage. Microbial spoilage of fermented cucumbers during bulk storage causes economic losses for producers. Current knowledge is insufficient to predict or control these losses. This study demonstrated that in the absence of oxygen, cucumbers fermented with 6% sodium chloride to pH 3.2 were not subject to spoilage. However, lactic acid was degraded

Dark ambient degradation of Bisphenol A and Acid Orange 8 as organic pollutants by perovskite SrFeO₃-δ metal oxide.

PubMed

Leiw, Ming Yian; Guai, Guan Hong; Wang, Xiaoping; Tse, Man Siu; Ng, Chee Mang; Tan, Ooi Kiang

2013-09-15

Current advanced oxidation processes (AOPs) are chemically and energetically intensive processes, which are undesirable for cost-effective and large-scale system water treatment and wastewater recycling. This study explored the Strontium Ferrite (SFO) metal oxide on the degradation of highly concentrated organic pollutants under dark ambient condition without any external stimulants. The SFO particles with single perovskite structure were successfully synthesized with a combined high temperature and high-energy ball milling process. An endocrine disruptor, Bisphenol A (BPA) and an azo dye, Acid Orange 8 (AO8) were used as probe organic pollutants. BPA was completely degraded with 83% of mineralization in 24 h while rapid decoloration of AO8 was achieved in 60 min and complete breakdown into primary intermediates and aliphatic acids occurred in 24 h under the treatment of dispersed SFO metal oxide in water. Such efficient degradation could be attributed to the enhanced adsorption of these anionic pollutants on positively charged ball-milled SFO metal oxide surface, resulted in higher degradation activity. Preliminary degradation mechanisms of BPA and AO8 under the action of SFO metal oxide were proposed. These results showed that the SFO metal oxide could be an efficient alternative material as novel advanced oxidation technology for low cost water treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Synergistic effect of acidity and extraframework position in faujasite on renewable p-xylene production

PubMed Central

2018-01-01

p-Xylene is a commodity chemical used for the manufacture of plastic bottles and textiles. For the biomass-based route from 2,5-dimethylfuran (DMF) and ethylene, the properties of the catalyst such as acidity effect, product selectivity and catalyst activity play an important role. To determine the effect of acidity and extraframework position in faujasite zeolite on p-xylene selectivity, type Y (Si/Al = 40 and Si/Al = 2.55) and X (Si/Al = 1.25) zeolites containing the extraframework Lewis acids Na+, K+, Li+, Ag+ and Cu+, and a Brønsted acid-containing zeolite, HY (Si/Al = 40), were prepared and tested for p-xylene production under solvent-free conditions and at low conversions (less than 35%). Here it is reported that NaX zeolite catalyses DMF and ethylene conversion to p-xylene with 91% selectivity at 30% conversion, which is better than the 25% p-xylene selectivity obtained when using HY at similar conversion. ANOVA was used to show that there is a synergistic effect between acidity and extraframework position on the rate of p-xylene production. At 7% DMF conversion, Lewis acids were more selective than the Brønsted acid tested (50 versus 30% p-xylene selectivity). p-Xylene selectivity is optimal when using Lewis acids with moderate acidity and extraframework positions located in the faujasite supercage (sites II and III). PMID:29892435

Equilibrium Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic C-H Bonds in P-(Para-substituted benzyl)triphenylphosphonium Cations and Related Cations.

PubMed

Zhang, Xian-Man; Fry, Albert J.; Bordwell, Frederick G.

1996-06-14

Equilibrium acidities (pK(HA)) of six P-(para-substituted benzyl)triphenylphosphonium (p-GC(6)H(4)CH(2)PPh(3)(+)) cations, P-allyltriphenylphosphonium cation, P-cinnamyltriphenylphosphonium cation, and As-(p-cyanobenzyl)triphenylarsonium cation, together with the oxidation potentials [E(ox)(A(-))] of their conjugate anions (ylides) have been measured in dimethyl sulfoxide (DMSO) solution. The acidifying effects of the alpha-triphenylphosphonium groups on the acidic C-H bonds in toluene and propene were found to be ca 25 pK(HA) units (34 kcal/mol). Introduction of an electron-withdrawing group such as 4-NO(2), 4-CN, or 4-Br into the para position of the benzyl ring in p-GC(6)H(4)CH(2)PPh(3)(+) cations resulted in an additional acidity increase, but introduction of the 4-OEt electron-donating group decreases the acidity. The equilibrium acidities of p-GC(6)H(4)CH(2)PPh(3)(+) cations were nicely linearly correlated with the Hammett sigma(-) constants of the substituents (G) with a slope of 4.78 pK(HA) units (R(2) = 0.992) (Figure 1). Reversible oxidation potentials of the P-(para-substituted benzyl)triphenylphosphonium ylides were obtained by fast scan cyclic voltammetry. The homolytic bond dissociation enthalpies (BDEs) of the acidic C-H bonds in these cations, estimated by combining their equilibrium acidities with the oxidation potentials of their corresponding conjugate anions, showed that the alpha-Ph(3)P(+) groups have negligible stabilizing or destabilizing effects on the adjacent radicals. The equilibrium acidity of As-(p-cyanobenzyl)triphenylarsonium cation is 4 pK(HA) units weaker than that of P-(p-cyanobenzyl)triphenylphosphonium cation, but the BDE of the acidic C-H bond in As-(p-cyanobenzyl)triphenylarsonium cation is ca 2 kcal/mol higher than that in P-(p-cyanobenzyl)triphenylphosphonium cation.

The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

PubMed

Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

2014-01-01

Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. Published by Elsevier B.V.

Potentiation of substance p by lysergic acid diethylamide in vivo

PubMed Central

Krivoy, W. A.

1961-01-01

In doses of 10 μg/kg or more, lysergic acid diethylamide enhanced the fourth potential (DR IV) of the dorsal root potential complex in the cat. Smaller doses of lysergic acid diethylamide did not in themselves alter the DR IV, but revealed an enhancement of the potential by substance P, which by itself had no effect. 2-Bromolysergic acid diethylamide had no action on the dorsal root potentials, but prevented the actions of lysergic acid diethylamide. PMID:13754427

Study of the acid-base properties of mineral soil horizons using pK spectroscopy

NASA Astrophysics Data System (ADS)

Shamrikova, E. V.; Vanchikova, E. V.; Ryazanov, M. A.

2007-11-01

The presence of groups 4 and 5 participating in acid-base equilibria was revealed in samples from mineral horizons of the gley-podzolic soil of the Komi Republic using pK spectroscopy (the mathematical processing of potentiometric titration curves for plotting the distribution of acid groups according to their pK values). The specific quantity of acid-base sites in soil samples was calculated. The contribution of organic and mineral soil components to the groups of acid-base sites was estimated. The pK values of groups determining the potential, exchangeable, and unexchangeable acidities were found. The heterogeneity of acid components determining different types of soil acidity was revealed.

Genomic study of the absorption mechanism of p-coumaric acid and caffeic acid of extract of Ananas comosus L. leaves.

PubMed

Dang, Yun-jie; Zhu, Chun-yan

2015-03-01

Cardiac disease has emerged as the leading cause of death worldwide, and food rich in phenolic acids has drawn much attention as sources of active substances of hypolipidemic drug. Ananas comosus L. (pineapple) is one of the most popular tropical and subtropical fruits. Isolated from pineapple leaves, EAL(Extract of Ananas Comosus L. Leaves) is rich in phenolic acids, such as p-coumaric acid, caffeic acid, and other phenolics, highly relevant to the putative cardiovascular-protective effects, which suggests its potential to be a new plant medicine for treatment of cardiac disease, but little is known about absorption, distribution, metabolism, and excretion of EAL in animals or human beings. In this study, we employed cDNA microarray, Caco-2 cell lines, and rat intestinal model to explore the absorption behavior of p-coumaric acid and caffeic acid in EAL. The permeation of 2 substances was concentration and time dependent. Results also indicated that monocarboxylic acid transporter was involved in the transepithelial transport of p-coumaric acid and caffeic acid. © 2015 Institute of Food Technologists®

Influence of polysorbate 80 and cyclopropane fatty acid synthase activity on lactic acid production by Lactobacillus casei ATCC 334 at low pH.

PubMed

Broadbent, J R; Oberg, T S; Hughes, J E; Ward, R E; Brighton, C; Welker, D L; Steele, J L

2014-03-01

Lactic acid is an important industrial chemical commonly produced through microbial fermentation. The efficiency of acid extraction is increased at or below the acid's pKa (pH 3.86), so there is interest in factors that allow for a reduced fermentation pH. We explored the role of cyclopropane synthase (Cfa) and polysorbate (Tween) 80 on acid production and membrane lipid composition in Lactobacillus casei ATCC 334 at low pH. Cells from wild-type and an ATCC 334 cfa knockout mutant were incubated in APT broth medium containing 3 % glucose plus 0.02 or 0.2 % Tween 80. The cultures were allowed to acidify the medium until it reached a target pH (4.5, 4.0, or 3.8), and then the pH was maintained by automatic addition of NH₄OH. Cells were collected at the midpoint of the fermentation for membrane lipid analysis, and media samples were analyzed for lactic and acetic acids when acid production had ceased. There were no significant differences in the quantity of lactic acid produced at different pH values by wild-type or mutant cells grown in APT, but the rate of acid production was reduced as pH declined. APT supplementation with 0.2 % Tween 80 significantly increased the amount of lactic acid produced by wild-type cells at pH 3.8, and the rate of acid production was modestly improved. This effect was not observed with the cfa mutant, which indicated Cfa activity and Tween 80 supplementation were each involved in the significant increase in lactic acid yield observed with wild-type L. casei at pH 3.8.

pH-Dependent Uptake of Fumaric Acid in Saccharomyces cerevisiae under Anaerobic Conditions

PubMed Central

Jamalzadeh, Elaheh; Verheijen, Peter J. T.; Heijnen, Joseph J.

2012-01-01

Microbial production of C4 dicarboxylic acids from renewable resources has gained renewed interest. The yeast Saccharomyces cerevisiae is known as a robust microorganism and is able to grow at low pH, which makes it a suitable candidate for biological production of organic acids. However, a successful metabolic engineering approach for overproduction of organic acids requires an incorporation of a proper exporter to increase the productivity. Moreover, low-pH fermentations, which are desirable for facilitating the downstream processing, may cause back diffusion of the undissociated acid into the cells with simultaneous active export, thereby creating an ATP-dissipating futile cycle. In this work, we have studied the uptake of fumaric acid in S. cerevisiae in carbon-limited chemostat cultures under anaerobic conditions. The effect of the presence of fumaric acid at different pH values (3 to 5) has been investigated in order to obtain more knowledge about possible uptake mechanisms. The experimental results showed that at a cultivation pH of 5.0 and an external fumaric acid concentration of approximately 0.8 mmol · liter−1, the fumaric acid uptake rate was unexpectedly high and could not be explained by diffusion of the undissociated form across the plasma membrane alone. This could indicate the presence of protein-mediated import. At decreasing pH levels, the fumaric acid uptake rate was found to increase asymptotically to a maximum level. Although this observation is in accordance with protein-mediated import, the presence of a metabolic bottleneck for fumaric acid conversion under anaerobic conditions could not be excluded. PMID:22113915

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats.

PubMed

Cardoso, Nancy; Pandolfi, Matías; Lavalle, Justina; Carbone, Silvia; Ponzo, Osvaldo; Scacchi, Pablo; Reynoso, Roxana

2011-12-01

The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level.

40 CFR 180.202 - p-Chlorophenoxyacetic acid; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific... established for the combined residues of the plant regulator p-chlorophenoxyacetic acid and its metabolite p...

40 CFR 180.202 - p-Chlorophenoxyacetic acid; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific... established for the combined residues of the plant regulator p-chlorophenoxyacetic acid and its metabolite p...

Acidic tumor microenvironment and pH-sensing G protein-coupled receptors.

PubMed

Justus, Calvin R; Dong, Lixue; Yang, Li V

2013-12-05

The tumor microenvironment is acidic due to glycolytic cancer cell metabolism, hypoxia, and deficient blood perfusion. It is proposed that acidosis in the tumor microenvironment is an important stress factor and selection force for cancer cell somatic evolution. Acidic pH has pleiotropic effects on the proliferation, migration, invasion, metastasis, and therapeutic response of cancer cells and the function of immune cells, vascular cells, and other stromal cells. However, the molecular mechanisms by which cancer cells and stromal cells sense and respond to acidic pH in the tumor microenvironment are poorly understood. In this article the role of a family of pH-sensing G protein-coupled receptors (GPCRs) in tumor biology is reviewed. Recent studies show that the pH-sensing GPCRs, including GPR4, GPR65 (TDAG8), GPR68 (OGR1), and GPR132 (G2A), regulate cancer cell metastasis and proliferation, immune cell function, inflammation, and blood vessel formation. Activation of the proton-sensing GPCRs by acidosis transduces multiple downstream G protein signaling pathways. Since GPCRs are major drug targets, small molecule modulators of the pH-sensing GPCRs are being actively developed and evaluated. Research on the pH-sensing GPCRs will continue to provide important insights into the molecular interaction between tumor and its acidic microenvironment and may identify new targets for cancer therapy and chemoprevention.

Identification of secretaglobin Scgb2a1 as a target for developmental reprogramming by BPA in the rat prostate.

PubMed

Wong, Rebecca Lee Yean; Wang, Quan; Treviño, Lindsey S; Bosland, Maarten C; Chen, Jing; Medvedovic, Mario; Prins, Gail S; Kannan, Kurunthachalam; Ho, Shuk-Mei; Walker, Cheryl Lyn

2015-01-01

Secretoglobins are a superfamily of secreted proteins thought to participate in inflammation, tissue repair, and tumorigenesis. Secretoglobin family 2A member 1 (Scgb2a1) is a component of prostatein, a major androgen-binding protein secreted by the rat prostate. Using a rat model for developmental reprogramming of susceptibility to prostate carcinogenesis, we identified, by RNA-seq, that Scgb2a1 is significantly upregulated (>100-fold) in the prostate of adult rats neonatally exposed to bisphenol A (BPA), with increased gene expression confirmed by quantitative RT-PCR and chromatin immunoprecipitation for histone H3 lysine 9 acetylation. Bisulfite analysis of both CpG islands located within 10 kb of the Scgb2a1 promoter identified significant hypomethylation of the CpG island upstream of the transcription start site of this gene in the reprogrammed prostate. These data suggest that expression of Scgb2a1 in the adult prostate could be epigenetically reprogrammed by BPA exposure during prostate development, with potential implications for cancer risk and response to chemotherapeutics associated with prostatein binding.

Interaction of melanin with proteins--the importance of an acidic intramelanosomal pH.

PubMed

Mani, I; Sharma, V; Tamboli, I; Raman, G

2001-06-01

Melanin is a highly irregular heteropolymer consisting of monomeric units derived from the enzymatic oxidation of the amino acid tyrosine. The process of melanin formation takes place in specialized acidic organelles (melanosomes) in melanocytes. The process of melanin polymerization requires an alkaline pH in vitro, and therefore, the purpose of an acidic environment in vivo remains a mystery. It is known that melanin is always bound to protein in vivo. It is also seen that polymerization in vitro at an acidic pH necessarily requires the presence of proteins. The effect of various model proteins on melanin synthesis and their interaction with melanin was studied. It was seen that many proteins could increase melanin synthesis at an acidic pH, and that different proteins resulted in the formation of different states of melanin, i.e., a precipitate or a soluble, protein-bound form. We also present evidence to show that soluble protein-bound melanin is present in vivo (in B16 cells as well as in B16 melanoma tissue). An acidic pH appeared to be necessary to ensure the formation of a uniform, very high molecular weight melano-protein complex. The interaction between melanin and proteins appears to be largely charge-dependent as evidenced by zeta potential measurements, and this interaction is also increased in an acidic pH. Thus, it appears that an acidic intramelanosomal pH is essential to ensure maximum interaction between protein and melanin, and also to ensure that all the melanin formed is protein-bound.

In silico Analysis for Predicting Fatty Acids of Black Cumin Oil as Inhibitors of P-Glycoprotein.

PubMed

Ali, Babar; Jamal, Qazi Mohd Sajid; Mir, Showkat R; Shams, Saiba; Al-Wabel, Naser A; Kamal, Mohammad A

2015-10-01

Black cumin oil is obtained from the seeds of Nigella sativa L. which belongs to family Ranunculaceae. The seed oil has been reported to possess antitumor, antioxidant, antibacterial, anti-inflammatory, hypoglycemic, central nervous system depressant, antioxidant, and immunostimulatory activities. These bioactivities have been attributed to the fixed oil, volatile oil, or their components. Seed oil consisted of 15 saturated fatty acids (17%) and 17 unsaturated fatty acids (82.9%). Long chain fatty acids and medium chain fatty acids have been reported to increase oral bioavailability of peptides, antibiotics, and other important therapeutic agents. In earlier studies, permeation enhancement and bioenhancement of drugs has been done with black cumin oil. In order to recognize the mechanism of binding of fatty acids to P-glycoprotein (P-gp), linoleic acid, oleic acid, margaric acid, cis-11, 14-eicosadienoic acid, and stearic acid were selected for in silico studies, which were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Template search with BLAST and HHblits has been performed against the SWISS-MODEL template library. The target sequence was searched with BLAST against the primary amino acid sequence of P-gp from Rattus norvegicus. The amount of energy needed by linoleic acid, oleic acid, eicosadienoic acid, margaric acid, and stearic acid to bind with P-gp were found to be - 10.60, -10.48, -9.95, -11.92, and - 10.37 kcal/mol, respectively. The obtained data support that all the selected fatty acids have contributed to inhibit P-gp activity thereby enhances the bioavailability of drugs. This study plays a significant role in finding hot spots in P-gp and may offer the further scope of designing potent and specific inhibitors of P-gp. Generation of 3D structure of fatty acid compounds from Black cumin oil and 3D homology modeling of Rat P glycoprotein as a receptor.Rat P-gp structure quality shows 88.5% residues in favored