BioDetection Systems

Amsterdam, Netherlands

BioDetection Systems

Amsterdam, Netherlands
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A Queen's University Belfast expert is leading a €4m international initiative to investigate whether natural toxins and manmade chemicals are creating potentially dangerous mixtures that affect our natural hormones and cause major illnesses such as cancer, obesity, diabetes or infertility. These chemicals include natural fungal toxins which can contaminate food and manmade chemicals such as pesticides. Dr Lisa Connolly, a leading academic in Toxin Food Safety and an expert in the Bioassay Analysis of Endocrine Disruptors at the University's Institute for Global Food Security, will lead the European Commission Funded study and collaborate with global experts in an international consortium involving thirteen organisations across nine countries to tackle the world-wide challenge. The four-year Marie Curie Innovative Training Network project PROTECTED (PROTECTion against Endocrine Disruptors) begins in January 2017 and the search is already underway for fifteen early stage researchers who will be trained as world class researchers that can develop innovative and entrepreneurial ways of dealing with this global challenge. Dr Connolly said: "Currently there is a world-wide shortage of researchers who can assess the impact of potentially dangerous natural and manmade endocrine disrupting chemicals and their mixtures on the hormone system which controls important functions within the body such as growth, development and fertility. We also need to understand whether these chemicals can cause illness by damaging the health of good bacteria in the gut." "Endocrine disruptors are suspected factors and sometimes proven agents behind several major human diseases, poor productivity in agricultural animals and stress upon ecosystems. If we can identify chemicals and mixtures of concern, we can use this knowledge to inform legislators, improve monitoring and reduce exposure." Queen's University Belfast will be awarded €1.2m of the funding with three researchers based at its world-leading Institute for Global Food Security. With its excellent academic record in food security and health, Queen's University Belfast is ideally suited for co-ordinating the project, further strengthening its leadership position in this field internationally. Dr Connolly added: "The exact effects of endocrine disruptors are difficult to assess so far because of the complexity of the chemical mixtures involved and the lack of efficient methods to assess their effects. "This newly established consortium is an exciting opportunity as it provides unique, world-leading and cutting-edge training for a new generation of experts who will have the ability to develop innovative analysis tools which will help protect the world from the real-life risks of these chemicals, improving health now and in the future." Speaking on behalf of all 13 organisations, Dr Marc Muller from Liege University in Belgium, said: "This expert approach is radically multi-disciplinary and deals with human or animal health using analytical chemistry, cellular tests and risk assessment of mixture effects." Professor Paul Fowler, from the University of Aberdeen in Scotland, added: "This exciting project and expert training network includes a crucial focus on human pregnancy. This is important because of the susceptibility of the developing baby in the womb to chemicals." Dr Connolly is collaborating with global experts in this international consortium including the Norwegian Institute for Public Health (Norway), the University of Aberdeen (Scotland), the Norwegian University of Life Sciences (Norway), The National Institute for Agricultural Research (France), the University Austral (Chile), the Norwegian Veterinary Institute (Norway), the University of Liege (Belgium), BioDetection Systems - an in vitro bioassay company based in The Netherlands, ProtoQSAR SL - a chemoinformatics & molecular modeling company in Spain, John Thompson & Sons Ltd - an animal feed company based in Northern Ireland, La Societe Wallone des Eaux - a water supplier in Belgium, and the Public Health Foundation of India. For further information please visit the Project Website: http://protected. Media inquiries to Emma Gallagher, Communications Officer at Queen's University on 028 9097 5384 and *Photograph and audio clips available at http://bit.

Gijsbers L.,Wageningen University | Van Eekelen H.D.L.M.,Wageningen University | Van Eekelen H.D.L.M.,Plant Research International | Nguyen T.H.,Wageningen University | And 5 more authors.
Food Chemistry | Year: 2012

The market for food products with additional health benefits is increasing rapidly and tools for identification of bio-functional characteristics of food items are essential. To facilitate the detection of beneficial effects of tomato on gene expression, methods to prepare tomato extracts suitable to test in the EpRE LUX assay and other cell-based reporter gene assays for health-related bioactivity mechanisms, were developed. An isoprenoid-containing chloroform extract of tomato fruit and most individual isoprenoids did not induce electrophile-responsive element (EpRE)-mediated gene expression. A semi-polar extract of tomato fruits, enzymatically hydrolysed to remove the glycosyl residues from the phenolic ingredients was able to induce EpRE-mediated luciferase expression at both mRNA and protein level, which might be partly due to the presence of quercetin, kaempferol, naringenin and naringenin chalcone. It was concluded that induction of EpRE-regulated genes, such as detoxifying phase II and antioxidant enzymes, may contribute to the beneficial health effects of tomato. © 2012 Elsevier Ltd. All rights reserved.

Gijsbers L.,Wageningen University | Man H.-Y.,BioDetection Systems | Kloet S.K.,Wageningen University | De Haan L.H.J.,Wageningen University | And 4 more authors.
Analytical Biochemistry | Year: 2011

Activation of peroxisome proliferator-activated receptor γ (PPARγ) by ligands is associated with beneficial health effects, including anti-inflammatory and insulin-sensitizing effects. The aim of the current study was to develop luciferase reporter gene assays to enable fast and low-cost measurement of PPARγ agonist and antagonist activity. Two reporter gene assays, PPARγ1 CALUX and PPARγ2 CALUX, were developed by stable transfection of U2OS cells with an expression vector for PPARγ1 or PPARγ2 and a pGL3-3xPPRE-tata-luc or pGL4-3xPPRE-tata-luc reporter construct, respectively. PPARγ1 CALUX and PPARγ2 CALUX cells showed similar concentration-dependent luciferase induction upon exposure to the PPARγ agonists rosiglitazone, troglitazone, pioglitazone, ciglitazone, netoglitazone, and 15-deoxy-Δ12,14-prostaglandin J2. The potency to induce luciferase decreased in the following order: rosiglitazone > troglitazone = pioglitazone > netoglitazone > ciglitazone. A concentration-dependent decrease in the response to 50 nM rosiglitazone was observed on the addition of PPARγ antagonist GW9662 or T0070907 in both PPARγ1 CALUX and PPARγ2 CALUX cells. The PPARα agonists WY14643 and fenofibrate failed to induce luciferase activity, confirming the specificity of these cell lines for PPARγ agonists. In conclusion, PPARγ1 CALUX and PPARγ2 CALUX cells provide a reliable and useful tool to screen (bio)chemicals for PPARγ agonist or antagonist activity. © 2011 Elsevier Inc. All rights reserved.

Houtman C.J.,The Water Laboratory | ten Broek R.,The Water Laboratory | de Jong K.,The Water Laboratory | Pieterse B.,BioDetection Systems | Kroesbergen J.,The Water Laboratory
Environmental Toxicology and Chemistry | Year: 2013

The river Meuse serves as a drinking-water source for more than 6 million people in France, Belgium, and The Netherlands. Pharmaceuticals and pesticides, both designed to be biologically active, are important classes of contaminants present in this river. The variation in the presence of pharmaceuticals in time and space in the Dutch part of the Meuse was studied using a multicomponent analytical method for pharmaceuticals combined with univariate and multivariate statistical analyses of the results. Trends and variation in time in the presence of pharmaceuticals were investigated in a dead-end side stream of the Meuse that serves as an intake point for the production of drinking water, and 93% of the selected compounds were detected. Highest concentrations were found for the antidiabetic metformin. Furthermore, a spatial snapshot of the presence of pharmaceuticals and pesticides was made along the river Meuse. Principal component analysis was successfully applied to reveal that wastewater-treatment plant effluent and water composition at the Belgian border were the main factors determining which compounds are found at different locations. The Dutch part of the river basin appeared responsible for approximately one-half of the loads of pharmaceuticals and pesticides discharged by the Meuse into the North Sea. The present study showed that multicomponent monitoring in combination with principal component analysis is a powerful tool to provide insight into contamination patterns in surface waters. © 2013 SETAC.

Suzuki G.,Japan National Institute of Environmental Studies | Tue N.M.,Ehime University | Malarvannan G.,Ehime University | Sudaryanto A.,Ehime University | And 7 more authors.
Environmental Science and Technology | Year: 2013

Indoor dust is a sink for many kinds of pollutants, including flame retardants (FRs), plasticizers, and their contaminants and degradation products. These pollutants can be migrated to indoor dust from household items such as televisions and computers. To reveal high-priority end points of and contaminant candidates in indoor dust, using CALUX reporter gene assays based on human osteosarcoma (U2OS) cell lines, we evaluated and characterized the endocrine-disrupting potencies of crude extracts of indoor dust collected from Japan (n = 8), the United States (n = 21), Vietnam (n = 10), the Philippines (n = 17), and Indonesia (n = 10) and for 23 selected FRs. The CALUX reporter gene assays used were specific for compounds interacting with the human androgen receptor (AR), estrogen receptor α (ERα), progesterone receptor (PR), glucocorticoid receptor (GR), and peroxisome proliferator-activated receptor γ2 (PPARγ2). Indoor dust extracts were agonistic to ERα, GR, and PPARγ2 and antagonistic against AR, PR, GR, and PPARγ2. In comparison, a majority of FRs was agonistic to ERα and PPARγ2 only, and some FRs demonstrated receptor-specific antagonism against all tested nuclear receptors. Hierarchical clustering clearly indicated that agonism of ERα and antagonism of AR and PR were common, frequently detected end points for indoor dust and tested FRs. Given our previous results regarding the concentrations of FRs in indoor dust and in light of our current results, candidate contributors to these effects include not only internationally controlled brominated FRs but also alternatives such as some phosphorus-containing FRs. In the context of indoor pollution, high-frequency effects of FRs such as agonism of ERα and antagonism of AR and PR are candidate high-priority end points for further investigation. © 2013 American Chemical Society.

van der Burg B.,BioDetection Systems
Reproductive toxicology (Elmsford, N.Y.) | Year: 2011

In spite of extensive research in the area over many decades, there is still a shortage of accepted alternative testing methods in reproductive toxicology. Of the variety of alternative methods developed for reproductive toxicity testing not a single one has reached regulatory acceptance. Although various standardized tests have been described, their predictability and applicability domains have so far not satisfactorily been defined. In the near future this situation will only change if new approaches are explored. Current regulatory needs in combination with technological innovations set the scene for rapid progress in this area.

Gijsbers L.,Wageningen University | Van Eekelen H.D.L.M.,Wageningen University | Van Eekelen H.D.L.M.,Plant Research International | De Haan L.H.J.,Wageningen University | And 9 more authors.
Journal of Agricultural and Food Chemistry | Year: 2013

Since beneficial effects related to tomato consumption partially overlap with those related to peroxisome proliferator-activated receptor γ (PPARγ) activation, our aim was to test extracts of tomato fruits and tomato components, including polyphenols and isoprenoids, for their capacity to activate PPARγ using the PPARγ2 CALUX reporter cell line. Thirty tomato compounds were tested; seven carotenoids and three polyphenols induced PPARγ2-mediated luciferase expression. Two extracts of tomato, one containing deglycosylated phenolic compounds and one containing isoprenoids, also induced PPARγ2-mediated expression at physiologically relevant concentrations. Furthermore, enzymatically hydrolyzed extracts of seven tomato varieties all induced PPARγ-mediated expression, with a 1.6-fold difference between the least potent and the most potent variety. The two most potent varieties had high flavonoid content, while the two least potent varieties had low flavonoid content. These data indicate that extracts of tomato are able to induce PPARγ-mediated gene expression in vitro and that some tomato varieties are more potent than others. © 2013 American Chemical Society.

Suzuki G.,Japan National Institute of Environmental Studies | Sato K.,Ehime University | Isobe T.,Japan National Institute of Environmental Studies | Takigami H.,Japan National Institute of Environmental Studies | And 2 more authors.
Science of the Total Environment | Year: 2015

Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were frequently detected in effluents collected from Japanese sewage treatment plants (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR) agonistic activities of ten pure synthetic GCs and selected STP effluents in Japan for assessment of the risks associated with the presence of GR agonists. The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX assay and their EC50 values were calculated for estimation of relative potencies (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol propionate>clobetasone butyrate>betamethasone 17-valerate>difluprednate>betamethasone 17,21-dipropionate>Dex>betamethasone>6α-methylprednisolone>prednisolone>cortisol. The GR agonistic activity in STP effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from <3.0-78ngL-1 (median: 29ngL-1, n=50). To evaluate the contribution of the target GCs, theoretical Dex-EQs were calculated by multiplying the concentrations of each GC by its respective REP. Our calculation of Dex-EQ contribution for individual GR agonists indicated that the well-known GCs cortisol and Dex should not be given priority for subsequent in vivo testing, monitoring and removal experiments, but rather the highly potent synthetic GCs clobetasol propionate and betamethasone 17-valerate (REP=28 and 3.1) as well as other unidentified compounds are important GR agonists in STP effluents in Japan. © 2015 Elsevier B.V.

PubMed | OFI Austrian Research Institute for Chemistry and Technology, Nestlé and BioDetection Systems
Type: | Journal: ALTEX | Year: 2016

The use of in vitro assays is important for the biodetection of endocrine active substances (EAS), reducing and replacing the in vivo studies required for regulatory assessment. However, this approach often fails to take into account the role of biotransformation on the activity of the test substances. A method incorporating an S9 metabolic system into the CALUX-reporter gene assays for estrogen receptor - and anti-androgen receptor -mediated activities has been developed. Methoxychlor, which is known to exhibit increased estrogenic and anti-androgenic activities after biotransformation, was used to set up the method in ERa and anti-AR CALUX. For the anti-androgenic assay, stanozolol was used as a competing agonist not metabolized by S9. The method was first applied in both agonist and antagonist modes to methoxychlor and bisphenol A, as positive and negative controls, respectively. Then, benzo(a)pyrene and flutamide were also tested for their potential of bioactivation. Co-treatment with S9 successfully increased the ER agonist and AR antagonist potency of methoxychlor; no change was observed for bisphenol A. Incubation with S9 also enhanced the anti-androgenic activity of flutamide. Interestingly, the metabolism of benzo(a)pyrene by the S9 resulted in an increased estrogen receptor-mediated transcriptional activation; any increase in the potency was only minor. It is likely that both enzyme kinetics and metabolite stability have influenced these effects, which would affect the composition of the final metabolite mixture. Together these results demonstrate the relevance of including biotransformation in in vitro bioassays for the detection of EAS.

PubMed | University of Veterinary Medicine Hannover and BioDetection Systems
Type: | Journal: Cell biology and toxicology | Year: 2016

Heterocyclic aromatic amines (HCAs) are compounds formed when meat or fish are cooked at high temperatures for a long time or over an open fire. To determine which pathways of toxicity are activated by HCAs, nine out of the ten HCAs known to be carcinogenic in rodents (2-amino-9H-pyrido[2,3-b]indole (AC), 2-aminodipyrido[1,2-a:3,2-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAC), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)) were tested in the estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor 2 (PPAR2), polycyclic aromatic hydrocarbons (PAH), Nrf2, and p53 CALUX reporter gene assays. Trp-P-1 was the only HCA that led to a positive response in the ER, PPAR2, and Nrf2 CALUX assays. In the PAH CALUX assay, Trp-P-2, MeAC, and AC induced luciferase activity to a greater extent than MeIQ and PhIP. In the p53 CALUX assay without a coupled metabolic activation, only Trp-P-1 and Trp-P-2 enhanced luciferase expression; when a metabolic activation step was coupled to the p53 CALUX assay, Trp-P-1, Glu-P-2, MeIQ, MeIQx, and PhIP induced a positive response. No HCA was positive in the AR and GR CALUX assays. Taken together, the results obtained show that the battery of CALUX assays performed in the present study can successfully be used to screen for molecular cell targets of carcinogenic compounds such as HCAs.

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