Hazardous waste sites contain complex mixtures of a wide variety of toxic chemicals. Unfortunately, development of rapid and inexpensive detection of specific chemicals or chemical classes in environmental and biological samples has been hampered by the lack of specific bioassay/biomarker systems. Accordingly, the overall goals of this project are to develop and validate a series of mechanistically-based cell and in vitro bioassays/biomarkers with applications to chemical detection and screening. Since effective development and application of bioassays/biomarkers is greatly facilitated by an understanding of the specific responses of cell to a given toxicant(s), each of the four proposed approaches will exploit information derived from analysis of the mechanisms by which selected chemicals affect cellular receptors, signal transduction pathways and/or cellular/enzyme functions.
In Aim 1, stably transfected cell lines will be developed as bioassays for ultra-low levels of dioxin-like or steroid hormone-like chemicals with the induction of receptor-dependent reporter gene expression. Chemical-specific recombinant AhRs will be generated to improve both cell and in vitro AhR based bioassay systems.
In Aim 2, human keratinocytes will be used to examine specific intracellular proteomic changes that occur in response to exposure to arsenicals and to identify potential biomarkers specifically altered by these chemicals.
In Aim 3, high throughput in vitro and cell-based bioassays will be used to examine the influence of Superfund chemicals on the production of regulatory lipids controlling cardiovascular diseases, inflammation and pajn.
In Aim 4, structure activity relationships will be established for a series of brominated flame retardants and their metabolites and the antimicrobial agent triclosan for their ability to alter ryanodine receptor signaling functions and the resulting impact on neuron growth and plasticity. In the final Aim, integrated bioassay/biomarkers will be used to identify and characterize the biochemical and toxicological effects of individual chemicals and complex mixtures of chemicals.
These studies will increase our basic knowledge of the biological/toxicological effects of various Superfund priority chemicals and will generate rapid mechanistically-based bioassay screening systems for detection of toxicants and toxicant exposure.
|Fritsch, Erika B; Stegeman, John J; Goldstone, Jared V et al. (2015) Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA. Aquat Toxicol 159:156-66|
|Flannery, Brenna M; Silverman, Jill L; Bruun, Donald A et al. (2015) Behavioral assessment of NIH Swiss mice acutely intoxicated with tetramethylenedisulfotetramine. Neurotoxicol Teratol 47:36-45|
|Anderson, Donald S; Silva, Rona M; Lee, Danielle et al. (2015) Persistence of silver nanoparticles in the rat lung: Influence of dose, size, and chemical composition. Nanotoxicology 9:591-602|
|Yang, Jun; Bratt, Jennifer; Franzi, Lisa et al. (2015) Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice. Am J Respir Cell Mol Biol 52:46-55|
|Davidson, R Andrew; Anderson, Donald S; Van Winkle, Laura S et al. (2015) Evolution of silver nanoparticles in the rat lung investigated by X-ray absorption spectroscopy. J Phys Chem A 119:281-9|
|Van Winkle, Laura S; Bein, Keith; Anderson, Donald et al. (2015) Biological dose response to PM2.5: effect of particle extraction method on platelet and lung responses. Toxicol Sci 143:349-59|
|Radhakrishnan, Rajeswaran; Suni, Ian I; Bever, Candace S et al. (2014) Impedance Biosensors: Applications to Sustainability and Remaining Technical Challenges. ACS Sustain Chem Eng 2:1649-1655|
|Das, Gautom Kumar; Bonifacio, Cecile S; De Rojas, Julius et al. (2014) Ultra-long Magnetic Nanochains for Highly Efficient Arsenic Removal from Water. J Mater Chem A Mater Energy Sustain 2:12974-12981|
|DeGroot, Danica E; Hayashi, Ai; Denison, Michael S (2014) Lack of ligand-selective binding of the aryl hydrocarbon receptor to putative DNA binding sites regulating expression of Bax and paraoxonase 1 genes. Arch Biochem Biophys 541:13-20|
|Ogunyoku, Temitope A; Young, Thomas M (2014) Removal of triclocarban and triclosan during municipal biosolid production. Water Environ Res 86:197-203|
Showing the most recent 10 out of 872 publications