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Prof. Lisa Connolly
Queen's University Belfast, UK

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0 Food Safety
0 High Content Screening
0 Hormones
0 Receptors
0 Reporter Gene Assays

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Reporter Gene Assays
Hormones
Endocrine disruptors
Receptors
human exposure
Endocrine Disruption
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High Content Screening
Food Safety
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Profile ImageM.J. Ruiz Laboratory of Toxicology, Fa...
Profile ImageTerje Svingen National Food Institute, Tec...
Profile ImagePauliina Damdimopoulou Division of Obstetrics and G...
Profile ImageAna M. Soto Tufts University School of M...
Profile ImageBart M. Gadella Department of Biomolecular H...
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Profile ImageMarie-Louise Scippo Department of Food Sciences,...
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Original paper
Published: 21 August 2021 in Exposure and Health
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In recent decades, the incidence of metabolic disorders has increased internationally. This increase has been linked to exposure to persistent organic pollutants (POPs), but little is known about the metabolic effects of realistic human exposure mixtures at relevant concentrations. In this study we tested if POPs, representing real-life exposure profiles and concentrations, were able to disrupt development and functions of adipose tissue in a direct way. The lipogenic potency of a POP mixture modelled on levels found in human blood as detected in the Scandinavian population was assessed. The Total mixture comprises 29 compounds divided over three groups: chlorinated (Cl), brominated (Br) and perfluorinated compounds (PFAA). Individual PFAA chemicals, the Total mixture and sub-mixtures (Cl, Br, PFAA, Cl + Br, Cl + PFAA and Br + PFAA) at five (× 1/10, × 1, × 50, × 100 and × 500) human blood levels were tested in an optimized high content analysis (HCA) 3T3-L1 adipogenesis assay. All exposures promoted adipocyte formation in 3T3-L1 cells at concentrations equivalent to × 1/10 human blood levels. PFAAs promoted lipid accumulation in 3T3-L1 cells at 33.6 pM (PFUnDA) and 390,460 pM (PFHxS). The Total mixture, and the Cl, PFAA, Cl + Br and Cl + PFAA sub-mixtures, started to promote lipid accumulation at × 1/10 human blood levels. This in vitro bioassay study assessed the adipogenic effects of POP mixtures modelled on real-life human exposure levels. The findings highlight that such exposures may alter adipose tissue development and function, thus potentially playing a role in the globally increasing escalation of metabolic disorders.

ACS Style

Y. Xie; H. F. Berntsen; K. E. Zimmer; E. Ropstad; S. Verhaegen; L. Connolly. Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells. Exposure and Health 2021, 1 -12.

AMA Style

Y. Xie, H. F. Berntsen, K. E. Zimmer, E. Ropstad, S. Verhaegen, L. Connolly. Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells. Exposure and Health. 2021; ():1-12.

Chicago/Turabian Style

Y. Xie; H. F. Berntsen; K. E. Zimmer; E. Ropstad; S. Verhaegen; L. Connolly. 2021. "Lipogenic Potency of Individual Perfluorinated Alkyl Acids (PFAAs) and Persistent Organic Pollutant (POP) Mixtures at Human Blood-Based Exposure Levels on Adipogenesis in 3T3-L1 Cells." Exposure and Health , no. : 1-12.

Journal article
Published: 10 June 2021 in Environmental Toxicology and Pharmacology
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Multiple substances are considered endocrine disrupting chemicals (EDCs). However, there is a significant gap in the early prioritization of EDC’s effects. In this work, in silico and in vitro methods were used to model estrogenicity. Two Quantitative Structure-Activity Relationship (QSAR) models based on Logistic Regression and REPTree algorithms were built using a large and diverse database of estrogen receptor (ESR) agonism. A 10-fold external validation demonstrated their robustness and predictive capacity. Mechanistic interpretations of the molecular descriptors (C-026, nArOH,PW5, B06[Br-Br]) used for modelling suggested that the heteroatomic fragments, aromatic hydroxyls, and bromines, and the relative bond accessibility areas of molecules, are structural determinants in estrogenicity. As validation of the QSARs, ESR transactivity of thirteen persistent organic pollutants (POPs) and suspected EDCs was tested in vitro using the MMV-Luc cell line. A good correspondence between predictions and experimental bioassays demonstrated the value of the QSARs for prioritization of ESR agonist compounds.

ACS Style

Elizabeth Goya-Jorge; Mazia Amber; Rafael Gozalbes; Lisa Connolly; Stephen J. Barigye. Assessing the chemical-induced estrogenicity using in silico and in vitro methods. Environmental Toxicology and Pharmacology 2021, 87, 103688 .

AMA Style

Elizabeth Goya-Jorge, Mazia Amber, Rafael Gozalbes, Lisa Connolly, Stephen J. Barigye. Assessing the chemical-induced estrogenicity using in silico and in vitro methods. Environmental Toxicology and Pharmacology. 2021; 87 ():103688.

Chicago/Turabian Style

Elizabeth Goya-Jorge; Mazia Amber; Rafael Gozalbes; Lisa Connolly; Stephen J. Barigye. 2021. "Assessing the chemical-induced estrogenicity using in silico and in vitro methods." Environmental Toxicology and Pharmacology 87, no. : 103688.

Original paper
Published: 10 May 2021 in Exposure and Health
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A total mixture of 29 persistent organic pollutants (POPs) modelled from Scandinavian blood concentrations was used to expose human A-498 kidney cells for 24 h over a concentration range spanning below to above blood level (1/10x, 1x, 50x, 100x, 500x). Its constituent submixtures (PFAA, Br, Cl) and co-mixtures (PFAA + Br, PFAA + Cl, Br + Cl) were also tested. Valinomycin (12 µM) was used as a cytotoxic comparative compound. Cell number (CN), nuclear area (NA), nuclear intensity (NI), mitochondrial membrane potential (MMP), and mitochondrial mass (MM) were assessed using high content analysis (HCA). Only the co-mixtures (PFAA + Cl, PFAA + Br) at 50x and 50x, 500x decreased CN, respectively. NI was increased by the total mixture at 500x and Cl mixture at all concentrations tested. MMP was increased by the total mixture at 100x and 500x, PFAA at 1x, Br + Cl and PFAA + Cl at 100x and 500x, respectively. MM was decreased by the total mixture at 500x. In contrast, valinomycin decreased CN and surviving cells showed a decrease in MMP and an increase in MM. In conclusion, POP exposure altered mitochondrial metabolism and induced cell death via an alternative mechanism to valinomycin. Only specific combinations of individual chemical classes, but not the total mixture, affected cell number.

ACS Style

Mazia Amber; Yuling Xie; Hanne Friis Berntsen; Karin Elizabeth Zimmer; Erik Ropstad; Steven Verhaegen; Lisa Connolly. Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro. Exposure and Health 2021, 1 -11.

AMA Style

Mazia Amber, Yuling Xie, Hanne Friis Berntsen, Karin Elizabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly. Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro. Exposure and Health. 2021; ():1-11.

Chicago/Turabian Style

Mazia Amber; Yuling Xie; Hanne Friis Berntsen; Karin Elizabeth Zimmer; Erik Ropstad; Steven Verhaegen; Lisa Connolly. 2021. "Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro." Exposure and Health , no. : 1-11.

Journal article
Published: 06 May 2021 in Journal of Exposure Science & Environmental Epidemiology
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Certain types of hair products are more commonly used by Black women. Studies show hair products contain several endocrine-disrupting chemicals that are associated with adverse health outcomes. As chemical mixtures of endocrine disruptors, hair products may be hormonally active, but this remains unclear. To assess the hormonal activity of commonly used Black hair products. We identified six commonly used hair products (used by >10% of the population) from the Greater New York Hair Products Study. We used reporter gene assays (RGAs) incorporating natural steroid receptors to evaluate estrogenic, androgenic, progestogenic, and glucocorticoid hormonal bioactivity employing an extraction method using bond elution prior to RGA assessment at dilutions from 50 to 500. All products displayed hormonal activity, varying in the amount and effect. Three samples showed estrogen agonist properties at levels from 12.5 to 20 ng/g estradiol equivalent concentrations All but one sample showed androgen antagonist properties at levels from 20 to 25 ng/g androgen equivalent concentrations. Four samples showed antagonistic and agonistic properties to progesterone and glucocorticoid. Hair products commonly used by Black women showed hormonal activity. Given their frequent use, exposure to hormonally active products could have implications for health outcomes and contribute to reproductive and metabolic health disparities.

ACS Style

Tamarra James-Todd; Lisa Connolly; Emma V. Preston; Marlee R. Quinn; Monika Plotan; Yuling Xie; Bharathi Gandi; Shruthi Mahalingaiah. Hormonal activity in commonly used Black hair care products: evaluating hormone disruption as a plausible contribution to health disparities. Journal of Exposure Science & Environmental Epidemiology 2021, 31, 476 -486.

AMA Style

Tamarra James-Todd, Lisa Connolly, Emma V. Preston, Marlee R. Quinn, Monika Plotan, Yuling Xie, Bharathi Gandi, Shruthi Mahalingaiah. Hormonal activity in commonly used Black hair care products: evaluating hormone disruption as a plausible contribution to health disparities. Journal of Exposure Science & Environmental Epidemiology. 2021; 31 (3):476-486.

Chicago/Turabian Style

Tamarra James-Todd; Lisa Connolly; Emma V. Preston; Marlee R. Quinn; Monika Plotan; Yuling Xie; Bharathi Gandi; Shruthi Mahalingaiah. 2021. "Hormonal activity in commonly used Black hair care products: evaluating hormone disruption as a plausible contribution to health disparities." Journal of Exposure Science & Environmental Epidemiology 31, no. 3: 476-486.

Journal article
Published: 13 January 2021 in Journal of Biotechnology
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Bis(2,4-di-tert-butylphenyl)Phosphate (bDtBPP) leaches out of polyethylene films used by the biopharmaceutical industry in single-use systems (SUS) for the culturing of drug producing cell lines. Previous studies found bDtBPP (0.025 – 0.110 mg/L) negatively affects Chinese hamster ovary (CHO) cell growth and productivity. Less information is known about the potential early stages of subtle pre-lethal cytotoxic effects of bDtBPP. This study aimed to investigate the pre-lethal cytotoxic effects in CHO-K1 cells of bDtBPP (0.005 - 0.25 μg/ml) at process relevant concentrations following 2, 24 and 48 h exposure, using high content analysis to investigate multiple pre-lethal cytotoxicity markers. After 48 h exposure, bDtBPP (0.005 - 0.25 μg/ml; P ≤ 0.001) increased nuclear intensity. A dose- and time-dependent reduction in mitochondrial mass was seen after exposure to bDtBPP. Reactive oxygen species increased after 2 h exposure to 0.25 μg/ml bDtBPP, 24 and 48 h exposure to 0.05 - 0.25 μg/ml bDtBPP (P ≤ 0.01 and P ≤ 0.001). BDtBPP induced subtle pre-lethal cytotoxic effects on CHO-K1 cellular health. This study highlights the cellular health benefits of the biopharmaceutical industry switching to alternative SUS plastics which do not leach bDtBPP, which may enhance CHO-K1 cell productivity.

ACS Style

Emma Harper; Yuling Xie; Lisa Connolly. Investigating the pre-lethal cytotoxic effects of bis(2,4-di-tert-butylphenyl)phosphate on Chinese hamster ovary cells using high content analysis. Journal of Biotechnology 2021, 328, 59 -71.

AMA Style

Emma Harper, Yuling Xie, Lisa Connolly. Investigating the pre-lethal cytotoxic effects of bis(2,4-di-tert-butylphenyl)phosphate on Chinese hamster ovary cells using high content analysis. Journal of Biotechnology. 2021; 328 ():59-71.

Chicago/Turabian Style

Emma Harper; Yuling Xie; Lisa Connolly. 2021. "Investigating the pre-lethal cytotoxic effects of bis(2,4-di-tert-butylphenyl)phosphate on Chinese hamster ovary cells using high content analysis." Journal of Biotechnology 328, no. : 59-71.

Journal article
Published: 09 December 2020 in Toxicology Letters
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Disruption of neurite outgrowth is a marker for neurotoxicity. Persistent organic pollutants (POPs) are potential developmental neurotoxicants. We investigated their effect on neurite outgrowth in PC12 rat pheochromocytoma cells, in absence or presence of nerve growth factor (NGF), an inducer of neuronal differentiation. Cells were exposed for 72 h to a defined mixture of POPs with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated perfluorooctane sulfonic acid (PFOS) alone, the most abundant compound in the POP mixture. Only higher concentrations of POP mixture reduced tetrazolium salt (MTT) conversion. High-content analysis showed a decrease in cell number, but no changes for nuclear and mitochondrial cellular health parameters. Robust glutathione levels were observed in NGF-differentiated cells. Live imaging, using the IncuCyte ZOOM platform indicated ongoing cell proliferation over time, but slower in presence of NGF. The pollutants did not inhibit neuritogenesis, but rather increased NGF-induced neurite length. PFOS induced neurite outgrowth to about 50 % of the level seen with the POP mixture. Neither the POP mixture nor PFOS affected neurite length in the absence of NGF. Our observations indicate that realistic complex mixtures of environmental pollutants can affect neuronal connectivity via NGF-induced neurite outgrowth.

ACS Style

Ajay Yadav; Mazia Amber; Denis Zosen; Nils Anders Labba; Eva Henriette Willemijn Huiberts; Johanna Samulin Erdem; Fred Haugen; Hanne Friis Berntsen; Shanbeh Zienolddiny; Ragnhild Elisabeth Paulsen; Erik Ropstad; Lisa Connolly; Steven Verhaegen. A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Toxicology Letters 2020, 338, 85 -96.

AMA Style

Ajay Yadav, Mazia Amber, Denis Zosen, Nils Anders Labba, Eva Henriette Willemijn Huiberts, Johanna Samulin Erdem, Fred Haugen, Hanne Friis Berntsen, Shanbeh Zienolddiny, Ragnhild Elisabeth Paulsen, Erik Ropstad, Lisa Connolly, Steven Verhaegen. A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Toxicology Letters. 2020; 338 ():85-96.

Chicago/Turabian Style

Ajay Yadav; Mazia Amber; Denis Zosen; Nils Anders Labba; Eva Henriette Willemijn Huiberts; Johanna Samulin Erdem; Fred Haugen; Hanne Friis Berntsen; Shanbeh Zienolddiny; Ragnhild Elisabeth Paulsen; Erik Ropstad; Lisa Connolly; Steven Verhaegen. 2020. "A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells." Toxicology Letters 338, no. : 85-96.

Journal article
Published: 23 October 2020 in International Journal of Environmental Research and Public Health
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Endocrine disrupting chemicals (EDCs) are exogenous chemicals found in food, consumer products, and the environment. EDCs are ubiquitous in modern life and exposure is associated with many negative health effects, such as reproductive disorders, metabolic disorders, and cancer. Scientists have deemed EDCs as a serious public health risk, yet the public’s perceptions of these chemicals is poorly understood. This study aimed to qualitatively explore how aware the public is of EDCs and their attitudes, beliefs, and perceptions of EDC risk. Thirty-four participants (aged 19–65 years) took part in the six focus groups. Discussions were transcribed verbatim and Nvivo 11 was used for thematic analysis. Our results indicated that awareness of EDCs was low. Themes of EDC risk perception included perceived control, perceived severity, and similarity heuristics. Risk alleviation strategies were also discussed. Future research should use quantitative methodology and a larger sample size to validate the findings from this study. Findings from this study may aid the development of effective risk communication strategies and public health interventions.

ACS Style

Melissa Kelly; Lisa Connolly; Moira Dean. Public Awareness and Risk Perceptions of Endocrine Disrupting Chemicals: A Qualitative Study. International Journal of Environmental Research and Public Health 2020, 17, 7778 .

AMA Style

Melissa Kelly, Lisa Connolly, Moira Dean. Public Awareness and Risk Perceptions of Endocrine Disrupting Chemicals: A Qualitative Study. International Journal of Environmental Research and Public Health. 2020; 17 (21):7778.

Chicago/Turabian Style

Melissa Kelly; Lisa Connolly; Moira Dean. 2020. "Public Awareness and Risk Perceptions of Endocrine Disrupting Chemicals: A Qualitative Study." International Journal of Environmental Research and Public Health 17, no. 21: 7778.

Review article
Published: 07 July 2020 in Archives of Toxicology
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Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause–effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman’s reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause–effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.

ACS Style

Hanna K. L. Johansson; Pauliina Damdimopoulou; Majorie B. M. van Duursen; Julie Boberg; Delphine Franssen; Marijke de Cock; Kersti Jääger; Magdalena Wagner; Agne Velthut-Meikas; Yuling Xie; Lisa Connolly; Pauline Lelandais; Severine Mazaud-Guittot; Andres Salumets; Monica Kam Draskau; Panagiotis Filis; Paul A. Fowler; Sofie Christiansen; Anne-Simone Parent; Terje Svingen. Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals. Archives of Toxicology 2020, 94, 3359 -3379.

AMA Style

Hanna K. L. Johansson, Pauliina Damdimopoulou, Majorie B. M. van Duursen, Julie Boberg, Delphine Franssen, Marijke de Cock, Kersti Jääger, Magdalena Wagner, Agne Velthut-Meikas, Yuling Xie, Lisa Connolly, Pauline Lelandais, Severine Mazaud-Guittot, Andres Salumets, Monica Kam Draskau, Panagiotis Filis, Paul A. Fowler, Sofie Christiansen, Anne-Simone Parent, Terje Svingen. Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals. Archives of Toxicology. 2020; 94 (10):3359-3379.

Chicago/Turabian Style

Hanna K. L. Johansson; Pauliina Damdimopoulou; Majorie B. M. van Duursen; Julie Boberg; Delphine Franssen; Marijke de Cock; Kersti Jääger; Magdalena Wagner; Agne Velthut-Meikas; Yuling Xie; Lisa Connolly; Pauline Lelandais; Severine Mazaud-Guittot; Andres Salumets; Monica Kam Draskau; Panagiotis Filis; Paul A. Fowler; Sofie Christiansen; Anne-Simone Parent; Terje Svingen. 2020. "Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals." Archives of Toxicology 94, no. 10: 3359-3379.

Journal article
Published: 01 July 2020 in Toxins
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Several studies have reported a wide range of severe health effects as well as clinical signs, when livestock animals are exposed to high concentration of mycotoxins. However, little is known regarding health effects of mycotoxins at low levels. Thus, a long-term feeding trial (between May 2017 and December 2019) was used to evaluate the effect of low doses of mycotoxin mixtures on performance of broiler chickens fed a naturally contaminated diet. In total, 18 successive broiler performance trials were carried out during the study period, with approximately 2200 one-day-old Ross-308 chicks used for each trial. Feed samples given to birds were collected at the beginning of each trial and analysed for multi-mycotoxins using a validated LC-MS/MS method. Furthermore, parameters including feed intake, body weight and feed efficiency were recorded on a weekly basis. In total, 24 mycotoxins were detected in samples analysed with deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FBs), apicidin, enniatins (ENNs), emodin and beauvericin (BEV), the most prevalent mycotoxins. Furthermore, significantly higher levels (however below EU guidance values) of DON, ZEN, FBs, BEV, ENNs and diacetoxyscirpenol (DAS) were detected in 6 of the 18 performance trials. A strong positive relationship was observed between broilers feed efficiency and DON (R2 = 0.85), FBs (R2 = 0.53), DAS (R2 = 0.86), ZEN (R2 = 0.92), ENNs (R2 = 0.60) and BEV (R2 = 0.73). Moreover, a three-way interaction regression model revealed that mixtures of ZEN, DON and FBs (p = 0.01, R2 = 0.84) and ZEN, DON and DAS (p = 0.001, R2 = 0.91) had a statistically significant interaction effect on the birds’ feed efficiency. As farm animals are often exposed to low doses of mycotoxin mixtures (especially fusarium mycotoxins), a cumulative risk assessment in terms of measuring and mitigating against the economic, welfare and health impacts is needed for this group of compounds.

ACS Style

Oluwatobi Kolawole; Abigail Graham; Caroline Donaldson; Bronagh Owens; Wilfred A. Abia; Julie Meneely; Michael J. Alcorn; Lisa Connolly; Christopher T. Elliott. Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study. Toxins 2020, 12, 433 .

AMA Style

Oluwatobi Kolawole, Abigail Graham, Caroline Donaldson, Bronagh Owens, Wilfred A. Abia, Julie Meneely, Michael J. Alcorn, Lisa Connolly, Christopher T. Elliott. Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study. Toxins. 2020; 12 (7):433.

Chicago/Turabian Style

Oluwatobi Kolawole; Abigail Graham; Caroline Donaldson; Bronagh Owens; Wilfred A. Abia; Julie Meneely; Michael J. Alcorn; Lisa Connolly; Christopher T. Elliott. 2020. "Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study." Toxins 12, no. 7: 433.

Journal article
Published: 10 June 2020 in Environmental Pollution
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TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and several other environment/food-borne toxic compounds induce their toxicity via the aryl hydrocarbon receptor (AhR). AhR is also modulated by various endogenous ligands e.g. highly potent tryptophan (Trp)-derivative FICZ (6-formylindolo[3,2-b]carbazole) and natural ligands abundant in the human diet e.g. polyphenols. Therefore, evaluating AhR species-specific responses is crucial for understanding AhR physiological functions, establishing risk assessments, and exploring the applicability of AhR mediators in drug and food industry towards human-based usages. We studied AhR transactivation of FICZ/TCDD in vitro in a time-dependent and species-specific manner using dioxin responsive luciferase reporter gene assays derived from rat (DR-H4IIE) and human (DR-HepG2) hepatoma cells. We observed for the first time that FICZ potency was similar in both cell lines and was 40 times higher than TCDD in DR-HepG2 cells. Depleting Trp-derivative endogenously produced ligands by using culture medium without Trp, resulted in 3-fold higher AhR activation upon adding FICZ in DR-H4IIE cells, in contrast to DR-HepG2 cells which revealed a fast degradation of FICZ induction from 10 h post-exposure to complete disappearance after 24 h. Seven polyphenols and a mixture thereof, chosen based on commercially recommended doses and adjusted to human realistic exposure, caused rat and human species-specific AhR responses. Two isoflavones (daidzein and genistein) induced rat AhR synergistic effects with FICZ and/or TCDD, while quercetin, chrysin, curcumin, resveratrol, and the mixture exerted a strong inhibitory effect on the human AhR. Strikingly, resveratrol and quercetin at their realistic nanomolar concentrations acted additively in the mixture to abolish human AhR activation induced by various TCDD concentrations. Taken together, these results illustrate the species-specific complexity of AhR transcriptional activities modulated by various ligands and highlight the need for studies of human-based approaches.

ACS Style

Thi Que Doan; Lisa Connolly; A. Igout; M. Muller; M.L. Scippo. In vitro differential responses of rat and human aryl hydrocarbon receptor to two distinct ligands and to different polyphenols. Environmental Pollution 2020, 265, 114966 .

AMA Style

Thi Que Doan, Lisa Connolly, A. Igout, M. Muller, M.L. Scippo. In vitro differential responses of rat and human aryl hydrocarbon receptor to two distinct ligands and to different polyphenols. Environmental Pollution. 2020; 265 ():114966.

Chicago/Turabian Style

Thi Que Doan; Lisa Connolly; A. Igout; M. Muller; M.L. Scippo. 2020. "In vitro differential responses of rat and human aryl hydrocarbon receptor to two distinct ligands and to different polyphenols." Environmental Pollution 265, no. : 114966.

Project report
Published: 01 May 2020 in International Journal of Molecular Sciences
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Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.

ACS Style

Majorie B. M. Van Duursen; Julie Boberg; Sofie Christiansen; Lisa Connolly; Pauliina Damdimopoulou; Panagiotis Filis; Paul A. Fowler; Bart M. Gadella; Jan Holte; Kersti Jääger; Hanna K. L. Johansson; Tianyi Li; Séverine Mazaud-Guittot; Anne-Simone Parent; Andres Salumets; Ana M. Soto; Terje Svingen; Agne Velthut-Meikas; Eva Bay Wedebye; Yuling Xie; Martin Van Den Berg. Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project. International Journal of Molecular Sciences 2020, 21, 3215 .

AMA Style

Majorie B. M. Van Duursen, Julie Boberg, Sofie Christiansen, Lisa Connolly, Pauliina Damdimopoulou, Panagiotis Filis, Paul A. Fowler, Bart M. Gadella, Jan Holte, Kersti Jääger, Hanna K. L. Johansson, Tianyi Li, Séverine Mazaud-Guittot, Anne-Simone Parent, Andres Salumets, Ana M. Soto, Terje Svingen, Agne Velthut-Meikas, Eva Bay Wedebye, Yuling Xie, Martin Van Den Berg. Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project. International Journal of Molecular Sciences. 2020; 21 (9):3215.

Chicago/Turabian Style

Majorie B. M. Van Duursen; Julie Boberg; Sofie Christiansen; Lisa Connolly; Pauliina Damdimopoulou; Panagiotis Filis; Paul A. Fowler; Bart M. Gadella; Jan Holte; Kersti Jääger; Hanna K. L. Johansson; Tianyi Li; Séverine Mazaud-Guittot; Anne-Simone Parent; Andres Salumets; Ana M. Soto; Terje Svingen; Agne Velthut-Meikas; Eva Bay Wedebye; Yuling Xie; Martin Van Den Berg. 2020. "Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project." International Journal of Molecular Sciences 21, no. 9: 3215.

Journal article
Published: 04 April 2020 in Toxins
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Cyanobacteria are cosmopolitan photosynthetic prokaryotes that can form dense accumulations in aquatic environments. They are able to produce many bioactive metabolites, some of which are potentially endocrine disrupting compounds, i.e., compounds that interfere with the hormonal systems of animals and humans. Endocrine disruptors represent potential risks to both environmental and human health, making them a global challenge. The aim of this study was to investigate the potential endocrine disrupting activities with emphasis on estrogenic effects of extracts from cultures of Microcystis or Planktothrix species. We also assessed the possible role of microcystins, some of the most studied cyanobacterial toxins, and thus included both microcystin-producing and non-producing strains. Extracts from 26 cyanobacterial cultures were initially screened in estrogen-, androgen-, and glucocorticoid-responsive reporter-gene assays (RGAs) in order to identify endocrine disruption at the level of nuclear receptor transcriptional activity. Extracts from selected strains were tested repeatedly in the estrogen-responsive RGAs, but the observed estrogen agonist and antagonist activity was minor and similar to that of the cyanobacteria growth medium control. We thus focused on another, non-receptor mediated mechanism of action, and studied the 17β-estradiol (natural estrogen hormone) biotransformation in human liver microsomes in the presence or absence of microcystin-LR (MC-LR), or an extract from the MC-LR producing M. aeruginosa PCC7806 strain. Our results show a modulating effect on the estradiol biotransformation. Thus, while 2-hydroxylation was significantly decreased following co-incubation of 17β-estradiol with MC-LR or M. aeruginosa PCC7806 extract, the relative concentration of estrone was increased.

ACS Style

Vittoria Mallia; Lada Ivanova; Gunnar S. Eriksen; Emma Harper; Lisa Connolly; Silvio Uhlig. Investigation of In Vitro Endocrine Activities of Microcystis and Planktothrix Cyanobacterial Strains. Toxins 2020, 12, 228 .

AMA Style

Vittoria Mallia, Lada Ivanova, Gunnar S. Eriksen, Emma Harper, Lisa Connolly, Silvio Uhlig. Investigation of In Vitro Endocrine Activities of Microcystis and Planktothrix Cyanobacterial Strains. Toxins. 2020; 12 (4):228.

Chicago/Turabian Style

Vittoria Mallia; Lada Ivanova; Gunnar S. Eriksen; Emma Harper; Lisa Connolly; Silvio Uhlig. 2020. "Investigation of In Vitro Endocrine Activities of Microcystis and Planktothrix Cyanobacterial Strains." Toxins 12, no. 4: 228.

Journal article
Published: 12 November 2019 in Toxins
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Contamination of animal feed with multiple mycotoxins is an ongoing and growing issue, as over 60% of cereal crops worldwide have been shown to be contaminated with mycotoxins. The present study was carried out to assess the efficacy of commercial feed additives sold with multi-mycotoxin binding claims. Ten feed additives were obtained and categorised into three groups based on their main composition. Their capacity to simultaneously adsorb deoxynivalenol (DON), zearalenone (ZEN), fumonisin B1 (FB1), ochratoxin A (OTA), aflatoxin B1 (AFB1) and T-2 toxin was assessed and compared using an in vitro model designed to simulate the gastrointestinal tract of a monogastric animal. Results showed that only one product (a modified yeast cell wall) effectively adsorbed more than 50% of DON, ZEN, FB1, OTA, T-2 and AFB1, in the following order: AFB1 > ZEN > T-2 > DON > OTA > FB1. The remaining products were able to moderately bind AFB1 (44–58%) but had less, or in some cases, no effect on ZEN, FB1, OTA and T-2 binding (

ACS Style

Oluwatobi Kolawole; Julie Meneely; Brett Greer; Olivier Chevallier; David S. Jones; Lisa Connolly; Christopher Elliott. Comparative In Vitro Assessment of a Range of Commercial Feed Additives with Multiple Mycotoxin Binding Claims. Toxins 2019, 11, 659 .

AMA Style

Oluwatobi Kolawole, Julie Meneely, Brett Greer, Olivier Chevallier, David S. Jones, Lisa Connolly, Christopher Elliott. Comparative In Vitro Assessment of a Range of Commercial Feed Additives with Multiple Mycotoxin Binding Claims. Toxins. 2019; 11 (11):659.

Chicago/Turabian Style

Oluwatobi Kolawole; Julie Meneely; Brett Greer; Olivier Chevallier; David S. Jones; Lisa Connolly; Christopher Elliott. 2019. "Comparative In Vitro Assessment of a Range of Commercial Feed Additives with Multiple Mycotoxin Binding Claims." Toxins 11, no. 11: 659.

Original article
Published: 13 September 2019 in Mycotoxin Research
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The contamination of feed with mycotoxins is a continuing feed quality and safety issue, leading to significant losses in livestock production and potential human health risks. Consequently, various methods have been developed to reduce the occurrence of mycotoxins in feed; however, feed supplementation with clay minerals or mineral adsorbents is the most prominent approach widely practiced by farmers and the feed industry. Due to a negatively charged and high surface area, pore volume, swelling ability, and high cation exchange capacity, mineral adsorbents including bentonite, zeolite, montmorillonite, and hydrated sodium calcium aluminosilicate can bind or adsorb mycotoxins to their interlayer spaces, external surface, and edges. Several studies have shown these substances to be partly or fully effective in counteracting toxic effects of mycotoxins in farm animals fed contaminated diets and thus are extensively used in livestock production to reduce the risk of mycotoxin exposure. Nevertheless, a considerable number of studies have indicated that these agents may also cause undesirable effects in farm animals. The current work aims to review published reports regarding adverse effects that may arise in farm animals (with a focus on pig and poultry) and potential interaction with veterinary substances and nutrients in feeds, when mineral adsorbents are utilized as a technological feed additive. Furthermore, results of in vitro toxicity studies of both natural and modified mineral adsorbents on different cell lines are reported. Supplementation of mycotoxin-contaminated feed with mineral adsorbents must be carefully considered by farmers and feed industry.

ACS Style

Christopher T. Elliott; Lisa Connolly; Oluwatobi Kolawole. Potential adverse effects on animal health and performance caused by the addition of mineral adsorbents to feeds to reduce mycotoxin exposure. Mycotoxin Research 2019, 36, 115 -126.

AMA Style

Christopher T. Elliott, Lisa Connolly, Oluwatobi Kolawole. Potential adverse effects on animal health and performance caused by the addition of mineral adsorbents to feeds to reduce mycotoxin exposure. Mycotoxin Research. 2019; 36 (1):115-126.

Chicago/Turabian Style

Christopher T. Elliott; Lisa Connolly; Oluwatobi Kolawole. 2019. "Potential adverse effects on animal health and performance caused by the addition of mineral adsorbents to feeds to reduce mycotoxin exposure." Mycotoxin Research 36, no. 1: 115-126.

Correction
Published: 09 September 2019 in Exposure and Health
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ACS Style

J. McComb; Ian Mills; Hanne Friis Berntsen; E. Ropstad; S. Verhaegen; L. Connolly. Correction to: Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro. Exposure and Health 2019, 12, 929 -929.

AMA Style

J. McComb, Ian Mills, Hanne Friis Berntsen, E. Ropstad, S. Verhaegen, L. Connolly. Correction to: Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro. Exposure and Health. 2019; 12 (4):929-929.

Chicago/Turabian Style

J. McComb; Ian Mills; Hanne Friis Berntsen; E. Ropstad; S. Verhaegen; L. Connolly. 2019. "Correction to: Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro." Exposure and Health 12, no. 4: 929-929.

Journal article
Published: 28 August 2019 in Environmental Pollution
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While humans are exposed to mixtures of persistent organic pollutants (POPs), their risk assessment is usually based on a chemical-by-chemical approach. To assess the health effects associated with mixed exposures, knowledge on mixture toxicity is required. Several POPs are potential ligands of the Aryl hydrocarbon receptor (AhR), which involves in xenobiotic metabolism and controls many biological pathways. This study assesses AhR agonistic and antagonistic activities of 29 POPs individually and in mixtures by using Chemical-Activated LUciferase gene eXpression bioassays with 3 transgenic cell lines (rat hepatoma DR-H4IIE, human hepatoma DR-Hep G2 and human mammary gland carcinoma DR-T47-D). Among the 29 POPs, which were selected based on their abundance in Scandinavian human blood, only 4 exerted AhR agonistic activities, while 16 were AhR antagonists in DR-H4IIE, 5 in DR-Hep G2 and 7 in DR-T47-D when tested individually. The total POP mixture revealed to be AhR antagonistic. It antagonized EC50 TCDD inducing AhR transactivation at a concentration of 125 and 250 and 500 fold blood levels in DR-H4IIE, DR-T47-D and DR-Hep G2, respectively, although each compound was present at these concentrations lower than their LOEC values. Such values could occur in real-life in food contamination incidents or in exposed populations. In DR-H4IIE, the antagonism of the total POP mixture was due to chlorinated compounds and, in particular, to PCB-118 and PCB-138 which caused 90% of the antagonistic activity in the POP mixture. The 16 active AhR antagonists acted additively. Their mixed effect was predicted successfully by concentration addition or generalized concentration addition models, rather than independent action, with only two-fold IC50 underestimation. We also attained good predictions for the full dose-response curve of the antagonistic activity of the total POP mixture.

ACS Style

Thi Que Doan; H.F. Berntsen; S. Verhaegen; E. Ropstad; Lisa Connolly; A. Igout; M. Muller; M.L. Scippo. A mixture of persistent organic pollutants relevant for human exposure inhibits the transactivation activity of the aryl hydrocarbon receptor in vitro. Environmental Pollution 2019, 254, 113098 .

AMA Style

Thi Que Doan, H.F. Berntsen, S. Verhaegen, E. Ropstad, Lisa Connolly, A. Igout, M. Muller, M.L. Scippo. A mixture of persistent organic pollutants relevant for human exposure inhibits the transactivation activity of the aryl hydrocarbon receptor in vitro. Environmental Pollution. 2019; 254 ():113098.

Chicago/Turabian Style

Thi Que Doan; H.F. Berntsen; S. Verhaegen; E. Ropstad; Lisa Connolly; A. Igout; M. Muller; M.L. Scippo. 2019. "A mixture of persistent organic pollutants relevant for human exposure inhibits the transactivation activity of the aryl hydrocarbon receptor in vitro." Environmental Pollution 254, no. : 113098.

Journal article
Published: 27 August 2019 in Environment International
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Human exposure to persistent organic pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P < 0.05). In the presence of testosterone the Cl and PFAA + Br mixtures at 1/10×, 1×, and 50× blood level antagonised AR translocation (P < 0.05). Taken together, some combinations of POP mixtures can interfere with AR translocation. However, in the transactivation assay, these combinations did not affect gene transactivation. Other POP combinations were identified here as modulators of AR-induced gene transactivation without affecting AR translocation. Thus, to fully evaluate the effect of environmental toxins on AR signalling, both types of assays need to be applied.

ACS Style

J. McComb; I.G. Mills; M. Muller; H.F. Berntsen; K.E. Zimmer; E. Ropstad; S. Verhaegen; L. Connolly. Human blood-based exposure levels of persistent organic pollutant (POP) mixtures antagonise androgen receptor transactivation and translocation. Environment International 2019, 132, 105083 .

AMA Style

J. McComb, I.G. Mills, M. Muller, H.F. Berntsen, K.E. Zimmer, E. Ropstad, S. Verhaegen, L. Connolly. Human blood-based exposure levels of persistent organic pollutant (POP) mixtures antagonise androgen receptor transactivation and translocation. Environment International. 2019; 132 ():105083.

Chicago/Turabian Style

J. McComb; I.G. Mills; M. Muller; H.F. Berntsen; K.E. Zimmer; E. Ropstad; S. Verhaegen; L. Connolly. 2019. "Human blood-based exposure levels of persistent organic pollutant (POP) mixtures antagonise androgen receptor transactivation and translocation." Environment International 132, no. : 105083.

Original paper
Published: 21 August 2019 in Exposure and Health
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Perfluoroalkyl acids (PFAAs) are detectable in human blood. PFAA exposure may contribute to androgen receptor (AR)-related health effects such as prostate cancer (PCa). In Norway and Sweden, exposures to PFAAs and PCa are very real concerns. In vitro studies conventionally do not investigate PFAA-induced AR disruption at human blood-based concentrations, thus limiting application to human health. We aim to determine the endocrine disrupting activity of PFAAs based upon human exposure levels, on AR transactivation and translocation. PFAAs (PFOS, PFOA, PFNA, PFDA, PFHxS, and PFUnDA) were tested at concentrations ranging from 1/10 × to 500 × relative to human blood based upon the exposure levels observed in a Scandinavian population. Translocation was measured by high content analysis (HCA) and transactivation was measured by reporter gene assay (RGA). No agonist activity (translocation or transactivation) was detected for any PFAAs. In the presence of testosterone, AR translocation increased following exposure to PFOS 1/10 × and 100 ×, PFOA 1/10 ×, and PFNA 1 × and 500 × (P < 0.05). In the presence of testosterone, PFOS 500 × antagonised AR transactivation, whereas PFDA 500 × increased AR transactivation (P < 0.05). PFAAs may contribute to AR-related adverse health effects such as PCa. PFAAs can disrupt AR signalling via two major components: translocation and transactivation. PFAAs which disrupt one signalling component do not necessarily disrupt both. Therefore, to fully investigate the disruptive effect of human exposure-based contaminants on AR signalling, it is imperative to analyse multiple molecular components as not all compounds induce a disruptive effect at the same level of receptor signalling.

ACS Style

J. McComb; Ian Mills; Hanne Friis Berntsen; E. Ropstad; S. Verhaegen; L. Connolly. Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro. Exposure and Health 2019, 12, 527 -538.

AMA Style

J. McComb, Ian Mills, Hanne Friis Berntsen, E. Ropstad, S. Verhaegen, L. Connolly. Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro. Exposure and Health. 2019; 12 (3):527-538.

Chicago/Turabian Style

J. McComb; Ian Mills; Hanne Friis Berntsen; E. Ropstad; S. Verhaegen; L. Connolly. 2019. "Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro." Exposure and Health 12, no. 3: 527-538.

Journal article
Published: 20 August 2019 in Toxicological Sciences
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Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to the Total mixture at ×500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at ×500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at ×1 blood levels. Cytotoxicity was present for ×100 and ×500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes.

ACS Style

Maeve Shannon; Yuling Xie; Steven Verhaegen; Jodie Wilson; Hanne F Berntsen; Karin E Zimmer; Erik Ropstad; Brian D Green; Lisa Connolly. A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor. Toxicological Sciences 2019, 172, 359 -367.

AMA Style

Maeve Shannon, Yuling Xie, Steven Verhaegen, Jodie Wilson, Hanne F Berntsen, Karin E Zimmer, Erik Ropstad, Brian D Green, Lisa Connolly. A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor. Toxicological Sciences. 2019; 172 (2):359-367.

Chicago/Turabian Style

Maeve Shannon; Yuling Xie; Steven Verhaegen; Jodie Wilson; Hanne F Berntsen; Karin E Zimmer; Erik Ropstad; Brian D Green; Lisa Connolly. 2019. "A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor." Toxicological Sciences 172, no. 2: 359-367.

Journal article
Published: 10 May 2019 in Food and Chemical Toxicology
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The mycotoxins zearalenone (ZEN) and alpha-zearalenone (α-ZOL), which are common contaminants of agri-food products, are known for their oestrogenic potential. In addition to mycotoxins, food may also contain pesticides with oestrogenic properties such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), raising the question on the potential effects of individual and combinations of these xeno-oestrogens on the action of natural oestrogens. The present study employed a mammalian reporter gene assay to assess the effects individual and binary combinations of these environmental and food-borne contaminants on oestrogen nuclear receptor (ER) transactivation. As expected, α-ZOL and ZEN exhibited the strongest oestrogenic potency (EC50: 0.27 ± 0.121 nM and 1.32 ± 0.0956 nM, respectively) whereas p,p'-DDT and p,p'-DDE had weak ER agonistic activity with the maximal response of 28.70 ± 2.97% and 18.65 ± 1.77%, respectively. Concurrent treatment of the mycotoxins and/or pesticides, individually or in binary combination, with 17β-oestradiol (E2) showed either additive, synergistic or antagonistic interactive effects on E2-mediated ER response, depending on the combination ratios, the concentration range of xeno-oestrogens, and the concentration of E2. This study highlights the importance of assessing the mixture effects of chemical contaminants in risk assessment, especially in the area of reproductive and developmental toxicity.

ACS Style

Ukpai A. Eze; John D. Huntriss; Michael N. Routledge; Yun Yun Gong; Lisa Connolly. The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays. Food and Chemical Toxicology 2019, 130, 68 -78.

AMA Style

Ukpai A. Eze, John D. Huntriss, Michael N. Routledge, Yun Yun Gong, Lisa Connolly. The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays. Food and Chemical Toxicology. 2019; 130 ():68-78.

Chicago/Turabian Style

Ukpai A. Eze; John D. Huntriss; Michael N. Routledge; Yun Yun Gong; Lisa Connolly. 2019. "The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays." Food and Chemical Toxicology 130, no. : 68-78.