Our objectives are to characterize poorly understood mechanistic processes that control sorption of Ahreceptor? ligands (AhRLs) to mineral surfaces, and then use these well-defined systems to probe the? bioavailability of sorbed AhRLs to bacteria and mammals. Since AhRLs tend to have exceptionally low water? solubilities, these highly toxic compounds exist in the environment predominantly as sorbed species. We? argue that clay minerals are a major, largely unrecognized sink for AhRLs in the environment. Our? preliminary studies and the literature suggest that clays may play a nearly equal or even dominant role to? that of organic matter in the immobilization of dioxins in soils. Our proposal has four specific aims: 1) To? measure sorption and sequestration of key AhRLs to clay minerals and to characterize the geochemical? controls on that sorption, 2) To determine the molecular mechanisms of such sorption through integrating? bulk results with spectroscopy and molecular simulation studies, thereby promoting more rational long-term? Superfund site stewardship, 3) To identify microbial genetic and functional responses to minerals themselves? and to mineral-adsorbed AhRLs in order to elucidate key mechanisms of microbial interaction with these? adsorbed compounds, and 4) To quantify the microbial functionality enabling bioavailability and? biodegradation of mineral-sorbed AhRLs by using fluorescent markers that are expressed with key microbial? responses. Thus our proposal supports the mission of the Superfund Basic Research and Training Program? because in Objective 1 we will work to """"""""identify and quantify chemical forms of the contaminants,"""""""" in? Objectives 1-2 we will assess """"""""the physical, chemical and biological processes affecting chemicals in? environmental media,"""""""" and in Objectives 3-4 we will link this work directly to bioavailability of Superfund? chemicals to bacteria and to mammals. Relevance of this research to public health: Many toxic organic contaminants are so insoluble in water that the main route of human exposure is through ingestion of adsorbed contaminants. We propose to characterize adsorption of dioxins and related compounds to clay minerals, and then use both bulk and? molecular methods to understand the effects of adsorption on the toxicity of the compound (to mice) and the? biodegradation of the compound (by soil bacteria), which is needed in remediation and risk assessment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004911-19
Application #
7599129
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
19
Fiscal Year
2008
Total Cost
$367,936
Indirect Cost
Name
Michigan State University
Department
Type
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Nault, Rance; Doskey, Claire M; Fader, Kelly A et al. (2018) Comparison of Hepatic NRF2 and Aryl Hydrocarbon Receptor Binding in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Treated Mice Demonstrates NRF2-Independent PKM2 Induction. Mol Pharmacol 94:876-884
Dornbos, Peter; LaPres, John J (2018) Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population. Toxicology 395:1-8
Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Interfacial Structure and Interaction of Kaolinite Intercalated with N-methylformamide Insight from Molecular Dynamics Modeling. Appl Clay Sci 158:204-210
Fader, Kelly A; Nault, Rance; Raehtz, Sandi et al. (2018) 2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice. Toxicol Appl Pharmacol 348:85-98
Zhang, Shuai; Liu, Qinfu; Cheng, Hongfei et al. (2018) Mechanism Responsible for Intercalation of Dimethyl Sulfoxide in Kaolinite: Molecular Dynamics Simulations. Appl Clay Sci 151:46-53
Zhang, Qiang; Li, Jin; Middleton, Alistair et al. (2018) Bridging the Data Gap From in vitro Toxicity Testing to Chemical Safety Assessment Through Computational Modeling. Front Public Health 6:261
Fader, K A; Nault, R; Kirby, M P et al. (2018) Corrigendum to ""Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity"" [Toxicol. Appl. Pharmacol. 321 (2017) 1-17]. Toxicol Appl Pharmacol 344:74
Konganti, Kranti; Ehrlich, Andre; Rusyn, Ivan et al. (2018) gQTL: A Web Application for QTL Analysis Using the Collaborative Cross Mouse Genetic Reference Population. G3 (Bethesda) 8:2559-2562
Zhang, Shuai; Liu, Qinfu; Gao, Feng et al. (2018) Molecular Dynamics Simulation of Basal Spacing, Energetics, and Structure Evolution of a Kaolinite-Formamide Intercalation Complex and Their Interfacial Interaction. J Phys Chem C Nanomater Interfaces 122:3341-3349
Fader, Kelly A; Nault, Rance; Kirby, Mathew P et al. (2017) Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity. Toxicol Appl Pharmacol 321:1-17

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