CHEEC Seed Grants: FY 2010

Iron-induced Alveolar Epithelial Cell Death Via Increase Ferritin Expression and p53 Activation
Investigators: A. Comellas, Department of Internal Medicine, and V. Grassian, Departments of Chemistry and Chemical and Biochemical Engineering, University of Iowa

Toxic Effects of Photolytic Transformation of Polybrominated Diphenyl Ethers (PBDEs) and Their Hydroxylated Compounds (OH-PBDEs)
Investigators: Y. Suh and G. Ludewig, Department of Occupational and Environmental Health, University of Iowa

Analysis of the non-target growth effects of metolachlor on human HepG2 cells
Investigator: K. Dhanwada, Department of Biology, University of Northern Iowa

Siloxanes in Chicago Air
Investigators: K. Hornbuckle, Department of Civil and Environmental Engineering, C. Stanier, Department of Chemical and Biochemical Engineering, The University of Iowa

 


Iron-induced Alveolar Epithelial Cell death Via Increase Ferritin Expression and p53 Activation
Investigators: A. Comellas, Department of Internal Medicine, and V. Grassian, Departments of Chemistry and Chemical and Biochemical Engineering, University of Iowa
A large amount of epidemiological and experimental studies indicate that particulate matter (PM), including, ultrafine particles, have close association with many respiratory and cardiovascular diseases. PM is a complex mixture of organic and inorganic airborne substance, generally composed of a core of ash or carbon, which is coated with organic molecules and transition metals of a broad size range. Between all the transition metals in PM composition, iron is almost always the most abundant in urban and rural areas. As a transition metal, iron is capable of generating reactive oxygen species (ROS) and contributing to oxidative stress, especially in the alveolar epithelium. Oxidative damage and cell death in the alveolar epithelium are the principal mechanisms attributed to PM and asbestos-induced lung injury. We hypothesize that iron content increases the expression of ferritin in alveolar epithelial cells (AEC), which in turn activates p53- dependent cell death pathway.

Publication:  Borcherding JA, Chen H, Caraballo JC, Baltrusaitis J, Pezzulo AA, Zabner J, Grassian VH, Comellas AP; Coal Fly Ash Impairs Airway Antimicrobial Peptides and Increases Bacterial Growth. PLOS ONE 2013; 8(2):es57673

Toxic Effects of Photolytic Transformation of Polybrominated Diphenyl Ethers (PBDEs) and Their Hydroxylated Compounds (OH-PBDEs)
Investigators: Y. Suh and G. Ludewig, Department of Occupational and Environmental Health, University of Iowa
The flame retardants polybrominated diphenyl ethers (PBDEs) and their hydroxylated compounds (OH-PBDEs) are ubiquitously found in the environment. Human exposure to PBDEs occurs primarily via contaminated house dust. PBDEs are photolytically, chemically or metabolically transformed to more bioavailable and toxic products such as OH-PBDEs. OH-PBDEs may be converted to polybrominated dibenzo-p-dioxins (PBDDs) by solar or artificial UV light. We hypothesize that light irradiation of PBDEs and OH-PBDEs generates cytotoxic, genotoxic and cancer-initiating reactive products and that co-exposure to TiO2-nanomaterials enhances this reaction. To study this hypothesis we propose to 1) measure cytotoxicity, oxidative stress, genotoxicity, and cytochrome P450 (CYP) enzyme induction (as an indicator of the production of AhR agonist formation) in human HaCaT keratinocytes after exposure to irradiatiated OH-PBDEs, 2) determine the toxic effects of irradiation-products of PBDEs + nano-sized titanium dioxide (TiO2) or PBDEs alone and 3) investigate physico-chemical changes of OH-PBDEs and PBDEs + the toxicological impacts of PBDEs and OHPBDEs.

Publication:  Suh YW, et al. UVA/B-Induced Formation of Free Radicals from Decabromodiphenyl ether. Environ Sci Technol. 2009; 43(7):2581-2588.

Analysis of the non-target growth effects of metolachlor on human HepG2 cells
Investigator: K. Dhanwada, Department of Biology, University of Northern Iowa
This pilot project will analyze the growth inhibiting effects of the herbicide metolachlor on non-target, human HepG2 cells. Metolachlor, a very commonly used herbicide in the United States, especially in the Midwest corn-belt, functions by inhibiting chlorophyll and protein synthesis in target plants. Herbicide exposure has led to detrimental effects in several organisms, notably affecting their growth and behavior, however, its mechanism of action in non-target organisms is not yet clear. The EPA does not currently have specific regulations for maximal limits allowed in drinking water. Growth studies from our lab demonstrate that increasing metolachlor concentrations and increasing time of exposure results in decreased growth of liver cells. The objective of this study is to elucidate a mechanism for decreased HepG2 cell growth after metolachlor exposure. Analyses will include assessing toxicity effects leading to necrosis, effects of apoptosis induction and alterations in cell cycle progression

Publication:  Hartnett S, Musah S, Dhanwada KR; Cellular Effects of Metolachlor Exposure on Human Liver (HepG2) Cells. Chemosphere 2013; 90:1258-1266

Siloxanes in Chicago Air
Investigators: K. Hornbuckle, Department of Civil and Environmental Engineering, C. Stanier, Department of Chemical and Biochemical Engineering, The University of Iowa
Siloxanes are organo-silicon compounds found in many industrial and consumer products like cosmetics, deodorants, and water repellants. More than one million tons of individual siloxanes, including those targeted in this proposal, are produced or imported in the US each year. As a result of their widespread use, they are found in wastewater and solid waste. They make their way into the environment through volatilization, wastewater discharge, and emission of landfill gases. This one-year pilot project focuses on the development of analytical methods for three cyclic siloxane compounds in air samples: octamethylcyclotetrasiloxane (D4); decamethylcyclopentasiloxane (D5); and dodecamethylcyclohexasiloxane (D6). The results will be used to develop a full-scale proposal for research on the emissions and transport of airborne siloxanes in Chicago and the surrounding Great Lakes.

Publications:  Yucuis RA, Stanier CO, Hornbuckle KC; Cyclic Siloxanes in Air, Including Identification of High Levels in Chicago and Distinct Diurnal Variation. Chemosphere 2013; pii S0045-6535 (13) 00359-7.

Bzdek BR, Horan AJ, Pennington MR, Janechek NJ, Baek J, Stanier CO, Johnston MV. Silicon is a Frequent Component of Atmospheric Nanoparticles. Environ Sci Technol 2014; 48(19):11137-11145.