@article{knuckles_dreher_2007, title={Fine oil combustion particle bioavailable constituents induce molecular profiles of oxidative stress, altered function, and cellular injury in cardiomyocytes}, volume={70}, ISSN={["1528-7394"]}, DOI={10.1080/15287390701459213}, abstractNote={Epidemiological studies have shown a positive association between exposure to air particulate matter (PM) pollution and adverse cardiovascular health effects in susceptible subpopulations such as those with pre-existing cardiovascular disease. The mechanism(s) through which pulmonary deposited PM, particularly fine PM2.5, PM with mass median aerodynamic diameter <2.5 μm, affects the cardiovascular system is currently not known and remains a major focus of investigation. In the present study, the transcriptosome and transcription factor proteome were examined in rat neonatal cardiomyocyte (RCM) cultures, following an acute exposure to bioavailable constituents of PM2.5 oil combustion particles designated residual oil fly ash leachate (ROFA-L). Out of 3924 genes examined, 38 genes were suppressed and 44 genes were induced following a 1-h exposure to 3.5 μg/ml of a particle-free leachate of ROFA (ROFA-L). Genomic alterations in pathways related to IGF-1, VEGF, IL-2, PI3/AKT, cardiovascular disease, and free radical scavenging, among others, were detected 1 h postexposure to ROFA-L. Global gene expression was altered in a manner consistent with cardiac myocyte electrophysiological remodeling, cellular oxidative stress, and apoptosis. ROFA-L altered the transcription factor proteome by suppressing activity of 24 and activating 40 transcription factors out of a total of 149. Genomic alterations were found to correlate with changes in transcription factor proteome. These acute changes indicate pathological molecular alterations, which may lead to possible chronic alterations to the cardiac myocyte. These data also potentially relate underlying cardiovascular effects from occupational exposure to ROFA and identify how particles from specific emission sources may mediate ambient PM cardiac effects.}, number={21}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Knuckles, Travis L. and Dreher, Kevin L.}, year={2007}, pages={1824–1837} }
 @article{roberts_malstrom_dreher_2007, title={In situ pulmonary localization of air pollution particle-induced oxidative stress}, volume={70}, ISSN={["1087-2620"]}, DOI={10.1080/15287390701551357}, abstractNote={Exposure to air particulate matter (PM) may be associated with increased morbidity and mortality. An improved understanding of the mechanism(s) by which PM induces adverse effects is needed. This preliminary study examined the ability to use unique bioluminescent technologies to identify acute localized areas of residual oil fly ash (ROFA)-induced, oxidative lung injury. Transgenic mice, in which luciferase (luc) expression was regulated by the heme oxygenase (HO)-1 promoter, were exposed by pharyngeal aspiration to either saline or 50 μg ROFA/mouse. HO-1-luc expression was determined at 2, 6, 12, and 24 h postexposure using luminescent quantification and Western blot analysis of lung protein extracts, as well as with a novel in situ pulmonary bioluminescence imaging approach. The different approaches for the detection of luciferase in lung protein extracts recovered from ROFA exposed HO-1-luc transgenic mice gave variable results. Pulmonary homogenate HO-1-luc levels were increased at 2 h and 24 h postexposure to ROFA when examined by chemilumescent and Western blot analyses, respectively. In situ bioluminescent imaging of pulmonary tissue sections detected ROFA-induced pulmonary luciferase expression by identifying highly localized increases in HO-1-luc expression at 12 h and 24 h postexposure. These results suggest that the variability observed in the methods of detection for luciferase may be due to a localization of cells expressing luciferase within tissue samples, demonstrating that the HO-1-luc transgenic mouse model is the preferred method to detect and pinpoint in vivo particle-induced, oxidative lung injury. The feasibility of using this in situ approach is a unique proof-of-concept application for the identification of localized sites of oxidative injury induced by environmental pollutants.}, number={22}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Roberts, Elizabeth S. and Malstrom, Scott E. and Dreher, Kevin L.}, year={2007}, pages={1929–1935} }
 @article{jiang_dreher_dye_li_richards_martin_adler_2000, title={Residual oil fly ash induces cytotoxicity and mucin secretion by guinea pig tracheal epithelial cells via an oxidant-mediated mechanism}, volume={163}, ISSN={["0041-008X"]}, DOI={10.1006/taap.1999.8886}, abstractNote={Inhalation of ambient air particulate matter (PM) is associated with pulmonary injury and inflammation. Using primary cultures of guinea pig tracheal epithelial (GPTE) cells as an in vitro model of airway epithelium, we examined effects of exposure to suspensions of six different emission and ambient air PM samples: residual oil fly ash (ROFA) from an electrical power plant; fly ash from a domestic oil burning furnace (DOFA); ambient air dust from St. Louis (STL), Ottawa (OT), and Washington, DC (WDC); and volcanic ash from the eruption of Mount Saint Helens (MSH) in 1980. Effects of these particulates on cell viability (assessed via LDH assay), secretion of mucin (measured by a monoclonal antibody-based ELISA), and steady-state mRNA levels of the mucin gene MUC2 were determined. ROFA was the most toxic of the dusts tested, as it significantly increased LDH release following a 24-h incubation with 50 microg/cm(2) ROFA. ROFA also enhanced MUC2 mRNA after 4-h exposure, and mucin secretion after 8 h. ROFA-induced mucin secretion and cytotoxicity were attenuated by the oxidant scavenger, dimethylthiourea (DMTU). ROFA exposure also depleted cells of glutathione (GSH). Relatedly, depletion of intracellular GSH by treatment of the cells with buthionine sulfoxamine (BSO) also provoked mucin secretion, as well as enhancing the secretory effect of ROFA when the two agents were added together. L-NMA, the nitric oxide synthase (NOS) inhibitor, did not affect ROFA-induced mucin secretion. Of the soluble transition metals in ROFA (nickel, iron, vanadium), only vanadium individually, or combinations of the metals containing vanadium, provoked secretion. The results suggest ROFA enhances mucin secretion and generates toxicity in vitro to airway epithelium via a mechanism(s) involving generation of oxidant stress, perhaps related to depletion of cellular antioxidant capacity. Deleterious effects of inhalation of ROFA in the respiratory tract in vivo may relate to these cellular responses. Vanadium, a component of ROFA, may be important in generating these reactions.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Jiang, NF and Dreher, KL and Dye, JA and Li, YH and Richards, JH and Martin, LD and Adler, KB}, year={2000}, month={Mar}, pages={221–230} }
 @article{jiang_dreher_li_martin_adler_1999, title={Residual oil fly ash (ROFA) increases mucin secretion and mucin gene expression in guinea pig airway epithelial cells in vitro.}, volume={159}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Jiang, N.-F. and Dreher, K. L. and Li, Y. and Martin, L. D. and Adler, K. B.}, year={1999}, pages={A888} }
 @article{dye_adler_richards_dreher_1999, title={Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression}, volume={277}, ISSN={["1040-0605"]}, DOI={10.1152/ajplung.1999.277.3.l498}, abstractNote={Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY}, author={Dye, JA and Adler, KB and Richards, JH and Dreher, KL}, year={1999}, month={Sep}, pages={L498–L510} }
 @article{adler_jiang_dye_dreher_1998, title={Exposure of differentiated rodent airway epithelial cells in vitro to particles of residual fly ash (ROFA) induces cytotoxicity and generation of reactive oxygen species.}, volume={10}, journal={Proceedings of the 10th International Colloquium on Lung Fibrosis}, author={Adler, K. B. and Jiang, N. F. and Dye, J. A. and Dreher, K. L.}, year={1998}, pages={26} }
 @article{adler_jiang_dye_dreher_1998, title={Particles of Residual Oil Fly Ash (ROFA) induce toxicity and mucin hypersecretion in rodent airway epithelial cells in vitro via an oxidant-mediated mechanism.}, volume={95}, DOI={10.1016/s0378-4274(98)80888-6}, journal={Toxicology Letters}, author={Adler, K. B. and Jiang, N. F. and Dye, J. A. and Dreher, K. L.}, year={1998}, pages={224} }
 @article{jiang_dreher_adler_1998, title={Residual oil fly ash (ROFA) induces cytotoxicity and enhances mucin secretion by guinea pig airway epithelial cells in vitro via an oxidant mediated mechanism.}, volume={157}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Jiang, N.-F. and Dreher, K. L. and Adler, K. B.}, year={1998}, pages={A150} }
 @article{dye_adler_rochelle_dreher_1998, title={Vanadium content and related oxidative stress appear to determine airway epithelial cell responses to emission source particulate matter.}, volume={12}, journal={FASEB Journal}, author={Dye, J. A. and Adler, K. B. and Rochelle, L. G. and Dreher, K. L.}, year={1998}, pages={A337} }
 @article{dye_adler_richards_dreher_1997, title={Airway epithelial cell responses to fly ash (ROFA) particles: contribution of soluble transition metals.}, volume={155}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Dye, J. A. and Adler, K. B. and Richards, J. H. and Dreher, K. L.}, year={1997}, pages={A197} }
 @article{dye_adler_richards_dreher_1996, title={Injury of rat tracheal epithelial cultures by exposure to residual oil fly ash (ROFA) involves generation of the hydroxyl radical.}, volume={153}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Dye, J. A. and Adler, K. B. and Richards, J. R. and Dreher, K. L.}, year={1996}, pages={A542} }
 @article{adler_krunkosky_fischer_rochelle_martin_dreher_jiang_dye_1996, title={Role or reactive oxygen and nitrogen species in the response of airway epithelium to particulates.}, volume={6}, journal={Proceedings of the 6th International Meeting of the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles.}, author={Adler, K. B. and Krunkosky, T. M. and Fischer, B. M. and Rochelle, L. G. and Martin, L. D. and Dreher, K. L. and Jiang, N. and Dye, J.}, year={1996}, pages={139} }