title: Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure.
abstract: Use of multi-walled carbon nanotubes (MWCNT) is growing which increases occupational exposures to these materials. Their toxic potential makes it important to have an in-depth understanding of the inflammation and disease that develops due to exposure. Epigenetics is one area of interest that has been quickly developing to assess disease processes due to its ability to change gene expression and thus the lung environment after exposure. In this study, promoter methylation of inflammatory genes (IFN-γ and TNF-α) was measured after MWCNT exposure using the pyrosequencing assay and found to correlate with initial cytokine production. In addition, methylation of a gene involved in tissue fibrosis (Thy-1) was also altered in a way that matched collagen deposition. In addition to using epigenetics to better understand disease processes, it has also been used as a biomarker of exposure and disease. In this study, global methylation was determined in the lung to ascertain whether MWCNT alter global methylation at the site of exposure and if those alterations coincide with disease development. Then, global methylation levels were determined in the blood to ascertain whether global methylation could be used as a biomarker of exposure in a more easily accessible tissue. Using the LuUminometric Methylation Assay (LUMA) and 5-Methylcytosine (5-mC) Quantification assay, we found that MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. This study provides initial data showing that alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development.
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Traci A
authors.initials: TA
authors.lastname: Brown
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Joong Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Virginia
authors.initials: V
authors.lastname: Porter
authors.affiliation: b College of Letters and Science, University of Wisconsin-Stevens Point , Stevens Point , WI , USA.
authors.forename: Harley
authors.initials: H
authors.lastname: Fredriksen
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Minju
authors.initials: M
authors.lastname: Kim
authors.affiliation: a Department of Biomedical and Pharmaceutical Sciences , Center for Environmental Health Sciences, University of Montana , Missoula , MT , USA and.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Cho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D019570:Inhalation Exposure; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D037742:Nanotubes, Carbon / Q000633:toxicity*; D016273:Occupational Exposure; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D018800:Thy-1 Antigens / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D037742:Nanotubes, Carbon; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: 5-mC; IFN-γ; LUMA; MWCNT; TNF-α; Thy-1; inflammation; methylation