@article{hilton_barosova_petri-fink_rothen-rutishauser_bereman_2019, title={Leveraging proteomics to compare submerged versus air-liquid interface carbon nanotube exposure to a 3D lung cell model}, volume={54}, ISSN={["0887-2333"]}, DOI={10.1016/j.tiv.2018.09.010}, abstractNote={With the emerging concern over the potential toxicity associated with carbon nanotube inhalation exposure, several in vitro methods have been developed to evaluate cellular responses. Since the major concern for adverse effects by carbon nanotubes is inhalation, various lung cell culture models have been established for toxicity testing, thus creating a wide variation of methodology. Limited studies have conducted side-by-side comparisons of common methods used for carbon nanotube hazard testing. The aim of this work was to use proteomics to evaluate global cellular response, including pro-inflammatory and pro-fibrotic mediators, of a 3D lung model composed of macrophages, epithelial cells, and fibroblasts which mimics the human alveolar epithelial tissue barrier. The cells were exposed to Mitsui 7 (M-7) multi-walled carbon nanotubes (MWCNT) under submerged and air-liquid interface (ALI) conditions and discovery proteomics identified 3500 proteins. The M-7 ALI exposure compared to control was found to increase expression in proteins related to oxidative stress that were not found to be enriched in submerged exposure. Comparison of MWCNT exposure methods, M-7 ALI exposure versus M-7 submerged exposure, yielded protein enrichment in pathways known to be associated with carbon nanotube exposure stress response, such as acute phase response signaling and NRF2-mediated oxidative stress response. This study demonstrates a comparison of commonly deployed carbon nanotube exposure methods. These data should be considered by the nanotoxicology community when interpreting or cross comparing in vitro exposure results.}, journal={TOXICOLOGY IN VITRO}, author={Hilton, G. and Barosova, H. and Petri-Fink, A. and Rothen-Rutishauser, B. and Bereman, M.}, year={2019}, month={Feb}, pages={58–66} }
 @article{hilton_taylor_hussain_dandley_griffith_garantziotis_parsons_bonner_bereman_2017, title={Mapping differential cellular protein response of mouse alveolar epithelial cells to multi-walled carbon nanotubes as a function of atomic layer deposition coating}, volume={11}, ISSN={["1743-5404"]}, DOI={10.1080/17435390.2017.1299888}, abstractNote={Abstract Carbon nanotubes (CNTs), a prototypical engineered nanomaterial, have been increasingly manufactured for a variety of novel applications over the past two decades. However, since CNTs possess fiber-like shape and cause pulmonary fibrosis in rodents, there is concern that mass production of CNTs will lead to occupational exposure and associated pulmonary diseases. The aim of this study was to use contemporary proteomics to investigate the mechanisms of cellular response in E10 mouse alveolar epithelial cells in vitro after exposure to multi-walled CNTs (MWCNTs) that were functionalized by atomic layer deposition (ALD). ALD is a method used to generate highly uniform and conformal nanoscale thin-film coatings of metals to enhance novel conductive properties of CNTs. We hypothesized that specific types of metal oxide coatings applied to the surface of MWCNTs by ALD would determine distinct proteomic profiles in mouse alveolar epithelial cells in vitro that could be used to predict oxidative stress and pulmonary inflammation. Uncoated (U)-MWCNTs were functionalized by ALD with zinc oxide (ZnO) to yield Z-MWCNTs or aluminum oxide (Al2O3) to yield A-MWCNTs. Significant differential protein expression was found in the following critical pathways: mTOR/eIF4/p70S6K signaling and Nrf-2 mediated oxidative stress response increased following exposure to Z-MWCNTs, interleukin-1 signaling increased following U-MWCNT exposure, and inhibition of angiogenesis by thrombospondin-1, oxidative phosphorylation, and mitochondrial dysfunction increased following A-MWCNT exposure. This study demonstrates that specific types of metal oxide thin film coatings applied by ALD produce distinct cellular and biochemical responses related to lung inflammation and fibrosis compared to uncoated MWCNT exposure in vitro.}, number={3}, journal={NANOTOXICOLOGY}, author={Hilton, Gina M. and Taylor, Alexia J. and Hussain, Salik and Dandley, Erinn C. and Griffith, Emily H. and Garantziotis, Stavros and Parsons, Gregory N. and Bonner, James C. and Bereman, Michael S.}, year={2017}, month={Apr}, pages={313–326} }
 @article{hilton_taylor_mcclure_parsons_bonner_bereman_2015, title={Toxicoproteomic analysis of pulmonary carbon nanotube exposure using LC-MS/MS}, volume={329}, ISSN={["0300-483X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000350519500009&KeyUID=WOS:000350519500009}, DOI={10.1016/j.tox.2015.01.011}, abstractNote={Toxicoproteomics is a developing field that utilizes global proteomic methodologies to investigate the physiological response as a result of adverse toxicant exposure. The aim of this study was to compare the protein secretion profile in lung bronchoalveolar lavage fluid (BALF) from mice exposed to non-functionalized multi-walled carbon nanotubes (U-MWCNTs) or MWCNTs functionalized by nanoscale Al2O3 coatings (A-MWCNT) formed using atomic layer deposition (ALD). Proteins were identified using liquid chromatography tandem mass spectrometry (LC-MS/MS), and quantified using a combination of two label-free proteomic methods: spectral counting and MS1 peak area analysis. On average 465 protein groups were identified per sample and proteins were first screened using spectral counting and the Fisher’s exact test to determine differentially regulated species. Significant proteins by Fisher’s exact test (p < 0.05) were then verified by integrating the intensity under the extracted ion chromatogram from a single unique peptide for each protein across all runs. A two sample t-test based on integrated peak intensities discovered differences in 27 proteins for control versus U-MWCNT, 13 proteins for control versus A-MWCNT, and 2 proteins for U-MWCNT versus A-MWCNT. Finally, an in-vitro binding experiment was performed yielding 4 common proteins statistically different (p < 0.05) for both the in-vitro and in-vivo study. Several of the proteins found to be significantly different between exposed and control groups are known to play a key role in inflammatory and immune response. A comparison between the in-vitro and in-vivo CNT exposure emphasized a true biological response to CNT exposure.}, journal={TOXICOLOGY}, author={Hilton, Gina M. and Taylor, Alexia J. and McClure, Christina D. and Parsons, Gregory N. and Bonner, James C. and Bereman, Michael S.}, year={2015}, month={Mar}, pages={80–87} }
 @article{hilton_hoppin_2014, title={Is Helicobacter Pylori an endogenous source of diethyl phthalate in humans?}, volume={134}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2014.08.019}, DOI={10.1016/j.envres.2014.08.019}, abstractNote={Monoethyl phthalate (MEP) is a metabolite used to assess exposure to diethyl phthalate (DEP). Helicobacter Pylori (HP) has been shown to produce DEP in laboratory studies. We used NHANES 1999–2000 data for 1623 adults to investigate whether HP seropositivity was associated with MEP levels. MEP levels were higher in individuals with HP seropositivity (p=0.0237), however the association differed by race. These results suggest that HP may be an endogenous source of DEP in some populations.}, journal={Environmental Research}, publisher={Elsevier BV}, author={Hilton, Gina M. and Hoppin, Jane A.}, year={2014}, month={Oct}, pages={402–404} }