Superfund sites typically contain complex mixtures of pollutants including chlorinated hydrocarbons, metals, and other toxic organic and inorganic compounds. Remediation of these sites results in some exposure of the surrounding population to airborne soil dust contaminated with hazardous substances or PM emitted from the treatment devices. Our researchers have shown EPFRs are present in at least some contaminated Superfund soils and formed in high concentration during incineration and thermal treatment of hazardous substances. These PM-associated EPFRs exist for days in the atmosphere and may continually form in contaminated soils. Once inhaled, they initiate and participate in catalytic chain cycles generating ROS and persist in biological media long enough to lead to pulmonary and cardiovascular damage. Since our discovery of EPFRs associated with Superfund sites is relatively recent, little is known about their mechanisms of toxicity. The toxic responses are thought to be mediated through the generation of reactive oxygen species (ROS), with several studies implicating the P450 system in this process. The goal of this study is to examine the roles of the P450 and HO-1 systems in the response to EPFR exposure within an organism. The hypothesis being addressed is that EPFRs associated with ultrafine particles (1) directly inhibit cytochrome P450-mediated activities, (2) decrease the expression of several P450 enzymes and increase the expression of ROS-protective enzymes (such as HO-1), and (3) alter P450-dependent ROS production. We will determine if decrease in P450 expression is the result of a ROS-mediated alteration in NFkB expression, where NFkB activation leads to decreases in P450 and increases in HO-1 expression that serve to limit oxidative damage in exposed tissues. Taken together, these studies are expected to provide novel information regarding how the P450 and HO-1 systems respond to EPFR exposure and affect EPFR-mediated toxicity.
Significant correlations between pulmonary and cardiovascular toxicity are associated with increased levels of airborne PM. Contaminated Superfund soils and PM emissions from thermal treatment of hazardous substance are especially toxic because they contain EPFRs of aromatic chlorinated hydrocarbons capable of generating reactive oxygen species. The goal of this study is to determine how drug and pollutant metabolism is affected by EPFR exposure, and to determine the mechanism of toxicity by these substances.
|Hijano, Diego R; Siefker, David T; Shrestha, Bishwas et al. (2018) Type I Interferon Potentiates IgA Immunity to Respiratory Syncytial Virus Infection During Infancy. Sci Rep 8:11034|
|Haywood, Benjamin J; White, John R; Cook, Robert L (2018) Investigation of an early season river flood pulse: Carbon cycling in a subtropical estuary. Sci Total Environ 635:867-877|
|Connick, J Patrick; Reed, James R; Backes, Wayne L (2018) Characterization of Interactions Among CYP1A2, CYP2B4, and NADPH-cytochrome P450 Reductase: Identification of Specific Protein Complexes. Drug Metab Dispos 46:197-203|
|Potter, Phillip M; Guan, Xia; Lomnicki, Slawomir M (2018) Synergy of iron and copper oxides in the catalytic formation of PCDD/Fs from 2-monochlorophenol. Chemosphere 203:96-103|
|Harmon, Ashlyn C; Hebert, Valeria Y; Cormier, Stephania A et al. (2018) Particulate matter containing environmentally persistent free radicals induces AhR-dependent cytokine and reactive oxygen species production in human bronchial epithelial cells. PLoS One 13:e0205412|
|Jaligama, Sridhar; Patel, Vivek S; Wang, Pingli et al. (2018) Radical containing combustion derived particulate matter enhance pulmonary Th17 inflammation via the aryl hydrocarbon receptor. Part Fibre Toxicol 15:20|
|Dugas, Tammy R (2018) Unraveling mechanisms of toxicant-induced oxidative stress in cardiovascular disease. Curr Opin Toxicol 7:1-8|
|Feld-Cook, Elisabeth E; Bovenkamp-Langlois, Lisa; Lomnicki, Slawo M (2017) Effect of Particulate Matter Mineral Composition on Environmentally Persistent Free Radical (EPFR) Formation. Environ Sci Technol 51:10396-10402|
|Chuang, Gin C; Xia, Huijing; Mahne, Sarah E et al. (2017) Environmentally Persistent Free Radicals Cause Apoptosis in HL-1 Cardiomyocytes. Cardiovasc Toxicol 17:140-149|
|Jaligama, Sridhar; Saravia, Jordy; You, Dahui et al. (2017) Regulatory T cells and IL10 suppress pulmonary host defense during early-life exposure to radical containing combustion derived ultrafine particulate matter. Respir Res 18:15|
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