Belongs to workpackage hazard


Beneficiary 3. RIVM - Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment of the Netherlands), Bilthoven, The Netherlands

Beneficiary descriptionn – RIVM is a recognised leading centre of expertise in health, nutrition and environmental protection, mainly working for the Dutch government. The mission of the Laboratory for Health Protection Research (GBO) of the RIVM is to identify, analyse, and quantify the hazards and risks of chemical and biological agents, of food, and of life-style factors for human health. In this context, there is a long-standing experience with toxicological studies in animal models.
Key personnel - Dr. Leo van der Ven is WP-2 leader. He is an experimental pathobiologist / toxicologist, experienced in toxicological pathology of endocrine disruption. Dr. Martijn Dollé will be responsible for transcriptome and epigenetic analyses. He is a molecular biologist with a background on structural and genetic changes in DNA and transcriptional variation using mouse models and human populations in relation to the metabolic syndrome and ageing. Prof. Dr. Harry van Steeg, molecular biologist, will act as a consultant for the molecular analyses, and Prof. Dr. Aldert Piersma, develomental toxicologist, as a consultant for the assessment of development in the mice F1 offspring and for the differentiation assays, Dr. Piet Wester, veterinary pathologist, as a consultant for the toxicological pathology. Dr. Eugčne Jansen is responsible for clinical chemical analysis of the material generated in the mice in vivo studies. Dr. Jeroen Pennings, molecular biologist, will assist in toxicogenomic analysis, and Prof. Dr. Wout Slob, bio-statistician, with data analysis and dose-response modelling.
Key role - RIVM will be responsible for the in vivo developmental studies in mice (Hazard Characterization, WP-2), which includes molecular biology (genetic and epigenetic) analysis of materials from the mice studies. In addition, RIVM will contribute to risk assessment through dose-response analysis (WP-3).

Key References
Van der Ven LT, Van de Kuil T, Verhoef A, Verwer CM, Lilienthal H, Leonards PE, Schauer UM, Cantón RF, Litens S, De Jong FH, Visser TJ, Dekant W, Stern N, Hĺkansson H, Slob W, Van den Berg M, Vos JG, Piersma AH. (2007). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology 245:76-89(2008)
Van der Ven LTM, van de Kuil A, Verhoef A, Fernández-Cantón R, Germer S, Lilienthal H, Schrenk D, Van den Berg M, Piersma AH, Leonards PEG, Vos JG (2006). Endocrine disrupting effects of selected brominated flame retardants in rats. Organohalogen Compounds 68:988-991.
Van der Ven LTM, Wester PW, Vos JG (2003). Histopathology as a tool for the evaluation of endocrine disruption in zebrafish. Environ.Toxicol.Chem., 22:908-913).
• Siemelink M, Verhoef A, Dormans JA, Span PN, Piersma AH (2002). Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring. Diabetologia 45:1397-403.
• Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EH, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD (2008). Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 51, 383-92.
Dollé M, Vijg J. Genome dynamics in aging mice. Genome Res. 2002;12:1732-1738
• Bahar R, Hartmann C, Rodriguez K, Denny A, Busuttil R, Dollé M, Calder R, Chisholm G, Pollock B, Klein C, Vijg J. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 2006;441:1011-1014.
• Lu Y, Dollé M, Imholz S, Slot R, Verschuren W, Wijmenga C, Feskens E, Boer J. Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations. J Lipid Res. 2008 in press.
Dollé M, Busuttil R, Garcia A, Wijnhoven S, van Drunen E, Niedernhofer L, van der Horst G, Hoeijmakers J, van Steeg H, Vijg J. Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice. Mutat Res. 2006; 596:22-35.
• Van Schothorst EM, Franssen-van Hal N, Schaap MM, Pennings J, Hoebee B, Keijer J. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis. Obes Res. 2005;13:1031-41.
• Bahar R, Hartmann C, Rodriguez K, Denny A, Busuttil R, Dollé M, Calder R, Chisholm G, Pollock B, Klein C, Vijg J. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 2006; 441:1011-1014.
• Berg S van de, Dollé M, Imholz S, van der A D, van ’t Slot R, Wijmenga C, Verschuren W, Strein C, Siezen C, Hoebee B, Feskens E, Boer J. Genetic variations in ragulatory pathways of fatty acid and glucose metabolism are associated with obesity-phenotypes: a population based cohort study. [submitted].
• Bruins W, Bruning O, Jonker MJ, Zwart E, van der Hoeven TV, Pennings JL, Rauwerda H, de Vries A, Breit TM. The absence of Ser389 phosphorylation in p53 affects the basal gene expression level of many p53-dependent genes and alters the biphasic response to UV exposure in mouse embryonic fibroblasts. Mol Cell Biol. 2008 28(6):1974-87.
• Janssen R, Bont L, Siezen CL, Hodemaekers HM, Ermers MJ, Doornbos G, van Slot R, Wijmenga C, Goeman JJ, Kimpen JL, van Houwelingen HC, Kimman TG, Hoebee B.Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007;196:826-34.
• Wijnhoven SW, Hoogervorst EM, de Waard H, van der Horst GT, van Steeg H.Tissue specific mutagenic and carcinogenic responses in NER defective mouse models. Mutat Res. 2007;614:77-94. Review.
• Baken KA, Vandebriel RJ, Pennings JL, Kleinjans JC, van Loveren H. Toxicogenomics in the assessment of immunotoxicity. Methods. 2007;41:132-41. Review.
• Van der Ven LT, Holbech H, Fenske M, Van den Brandhof EJ, Gielis-Proper FK, Wester PW.Vitellogenin expression in zebrafish Danio rerio: evaluation by histochemistry, immunohistochemistry, and in situ mRNA hybridisation. Aquat Toxicol. 2003;65:1-11
• van Steeg H, de Vries A, van Oostrom CTh, van Benthem J, Beems RB, van Kreijl CF. DNA repair-deficient Xpa and Xpa/p53+/- knock-out mice: nature of the models. Toxicol Pathol. 2001;29 Suppl:109-16. Review.

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