Schadelijke stoffen in scholekstereieren; responsmetingen in bioassays ter bepaling van risico's van contaminanten in eieren van scholeksters uit het Zeehavenkanaal

In het verleden zijn door het RIKZ in het Zeehavenkanaal te Delfzijl hoge hexachloorbenzeengehalten gemeten. Na sanering voldeed de onderwaterbodem voor hexachloorbenzeen echter nog steeds niet aan de normen voor het baggerbeheer. In eieren van scholeksters die foerageren in het met hexachloorbenzeen verontreinigde gebied, zijn ook verhoogde concentraties gemeten. De vraag is of deze verhoogde concentraties hexachloorbenzeen en eventuele andere verontreinigingen nadelige effecten hebben op de scholeksters. Uit het onderzoek waarvan de resultaten in dit rapport beschreven staan, blijkt dat de in de eieren aanwezige stoffen in staat zijn om effecten bij vogels te veroorzaken

Effects of environmental and natural estrogens on vitellogenin production in hepatocytes of the brown frog (Rana temporaria)

The objective of this study was to investigate the ability of the natural estrogens and synthetic estrogens as well as the estrogen mimics to induce estrogen-receptor mediated vitellogenesis in primary hepatocytes of the brown frog (Rana temporaria). Based on EC50 values the following order was determined for the potency of the estrogens: 17beta-estradiol (EC50: 19-43 nM) approximate to ethynylestradiol (EC50: 13-80 nM) > estrone (EC50: 218-241 nM) > DES (EC50: 338-3537 nM). Exposure to bisphenol A and methoxychlor concentrations up to 100 muM did not have any effect on in vitro vitellogenesis. (C) 2004 Elsevier B.V. All rights reserved

Introduction of ethoxy-resorufin-o-deethylase activity by halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons in primary hepatocytes of the green frog (Rana esculenta)

In this study, we measured the ethoxy-resorufin-O-deethylase (EROD) activity in primary hepatocytes of the common green frog Rana esculenta as a biomarker for cytochrome P4501A induction. We exposed hepatocytes derived from male and female frogs to several halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), polychlorinated biphenyls (PCB-126, PCB-118). and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP), chrysene, anthracene, and pyrene. Exposure to PCB-118, anthracene, and pyrene, up to 1 μ M, did not induce EROD activity, whereas TCDD and PCDF induced EROD activity maximally. In our primary frog hepatocytes, exposure to chrysene and BaP resulted in median effective concentration values (EC50) in the high nM range (82-1035 nM). Exposure to TCDD, PCDF and PCB-126 resulted in EC50 values of 0.4 to 8, 0.07 to 0.7, and 3 to 133 nM, respectively, which is in the same range as EC50 values found in primary hepatocytes of birds. Compared to our frog hepatocytes, primary rat hepatocytes seem to be more sensitive to TCDD, chrysene. and BaP

Effects of environmental and natural estrogens on vitellogenin production in hepatocytes of the brown frog (Rana temporaria)

The objective of this study was to investigate the ability of the natural estrogens and synthetic estrogens as well as the estrogen mimics to induce estrogen-receptor mediated vitellogenesis in primary hepatocytes of the brown frog (Rana temporaria). Based on EC50 values the following order was determined for the potency of the estrogens: 17beta-estradiol (EC50: 19-43 nM) approximate to ethynylestradiol (EC50: 13-80 nM) > estrone (EC50: 218-241 nM) > DES (EC50: 338-3537 nM). Exposure to bisphenol A and methoxychlor concentrations up to 100 muM did not have any effect on in vitro vitellogenesis. (C) 2004 Elsevier B.V. All rights reserved

Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions. Six early life immune causal networks, each compromising a different time period in early life (the 1st, 2nd, 3rd trimester of gestations, birth, newborn, and infant period), were generated. Thereto information was extracted and structured from early life literature using the automated text mining and machine learning tool: Integrated Network and Dynamical Reasoning Assembler (INDRA). The tool identified relevant entities (e.g., genes/proteins/metabolites/processes/diseases), extracted causal relationships among these entities, and assembled them into early life-immune causal networks. These causal early life immune networks were denoised using GeneMania, enriched with data from the gene-disease association database DisGeNET and Gene Ontology resource tools (GO/GO-SLIM), inferred missing relationships and added expert knowledge to generate information-dense early life immune networks. Analysis of the six early life immune networks by PageRank, not only confirmed the central role of the "commonly used immune markers" (e.g., chemokines, interleukins, IFN, TNF, TGFB, and other immune activation regulators (e.g., CD55, FOXP3, GATA3, CD79A, C4BPA), but also identified less obvious candidates (e.g., CYP1A2, FOXK2, NELFCD, RENBP). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (TNF, IL6, IL10, CD4, FOXP3, IL4, NELFCD, CD79A, IL5, RENBP, and IFNG), and also genes that were only described in certain early life period(s). Concluding, here we describe a network-based approach that provides a science-based and systematical method to explore the functional development of the early life immune system through time. This systems approach aids the generation of a testing strategy for the safety and efficacy of early life immune modulation by predicting the key candidate markers during different phases of early life immune development