The scientific theme for this competitive renewal continues the theme from the grant submission: effects of exposures to environmentally hazardous substances on reproduction and development in humans and wildlife. Special emphasis is placed on substances commonly encountered as a result of improperly managed waste disposal. The chemicals under study are organics, both halogenated and nonhalogenated compounds. The program will focus on the underlying mechanics of xenobiotics/ endocrine interactions and their effects to allow a better understanding of the implications of perturbations of reproductive and developmental processes by hazardous substances in the environment. Nine projects (5 biomedical and 4 nonbiomedical) will study: 1) Epidemiologic studies of neurodevelopment of a population exposed to perchlorethylene (PCE, a peroxisome proliferators) in drinking water, and epidemiologic techniques to study similar environmental problems (two biomedical projects); 2) receptor based mechanistic studies of the role of intracellular receptors and signaling pathways in the development of organisms and tissues (receptors/pathway: Ah receptor, AhR; peroxisome proliferator activated receptor, PPAR; estrogen receptor, ER; androgen receptor, AR; MAP kinase pathway) for important xenobiotics (planar halogenated aromatic hydrocarbons, PHAHs; polycyclic aromatic hydrocarbons, PAHs; and peroxisome proliferators, especially phthalates), and three biomedical projects; 3) Mechanisms of toxicity and resistance of fish populations to PHAHs and xenoestrogens involving receptors (AhRs, PPARs, and ERs) and cytochrome P450s (1 non-biomedical project and 2 biomedical); 4) studies of the mechanistic basis for reproductive and developmental effects on observed wildlife (including those mediated by AhR and ER) exposed to a complex mixture in surface water from a Superfund Site via groundwater and sediment (1 non-biomedical); 5) Mechanisms of oxidative dechlorination by an abiotic non-heme iron catalyst for remediation of a wide variety of xenobiotics, including all those under study in other projects.
| Vieira, Verónica M; Hansen, Johnni; Gredal, Ole et al. (2018) Spatial analyses of ALS incidence in Denmark over three decades. Amyotroph Lateral Scler Frontotemporal Degener 19:275-284 |
| Tomsho, Kathryn S; Basra, Komal; Rubin, Staci M et al. (2018) Community reporting of ambient air polychlorinated biphenyl concentrations near a Superfund site. Environ Sci Pollut Res Int 25:16389-16400 |
| Aschengrau, Ann; Gallagher, Lisa G; Winter, Michael et al. (2018) Modeled exposure to tetrachloroethylene-contaminated drinking water and the occurrence of birth defects: a case-control study from Massachusetts and Rhode Island. Environ Health 17:75 |
| Weisskopf, Marc G; Seals, Ryan M; Webster, Thomas F (2018) Bias Amplification in Epidemiologic Analysis of Exposure to Mixtures. Environ Health Perspect 126:047003 |
| Narasimhan, Supraja; Stanford Zulick, Elizabeth; Novikov, Olga et al. (2018) Towards Resolving the Pro- and Anti-Tumor Effects of the Aryl Hydrocarbon Receptor. Int J Mol Sci 19: |
| Rothhammer, Veit; Borucki, Davis M; Kenison, Jessica E et al. (2018) Detection of aryl hydrocarbon receptor agonists in human samples. Sci Rep 8:4970 |
| Lille-Langøy, Roger; Karlsen, Odd André; Myklebust, Line Merethe et al. (2018) Sequence variations in pxr (nr1i2) from zebrafish (Danio rerio) strains affect nuclear receptor function. Toxicol Sci : |
| Lemaire, Benjamin; Karchner, Sibel I; Goldstone, Jared V et al. (2018) Molecular adaptation to high pressure in cytochrome P450 1A and aryl hydrocarbon receptor systems of the deep-sea fish Coryphaenoides armatus. Biochim Biophys Acta Proteins Proteom 1866:155-165 |
| Eide, Marta; Rydbeck, Halfdan; Tørresen, Ole K et al. (2018) Independent losses of a xenobiotic receptor across teleost evolution. Sci Rep 8:10404 |
| Watt, James; Baker, Amelia H; Meeks, Brett et al. (2018) Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice. J Cell Physiol 233:7007-7021 |
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