title: In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles.
abstract: Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.
authors.affiliation: a Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health , Boston , MA , USA .
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: b Department of Environmental and Occupational Health , College of Public Health, University of Arkansas for Medical Sciences , Little Rock , AR , USA .
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.affiliation: a Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health , Boston , MA , USA .
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Pirela
authors.affiliation: c Department of Systems Biology , Harvard Medical School , Boston , MA , USA , and.
authors.forename: Jodene K
authors.initials: JK
authors.lastname: Moore
authors.affiliation: d Department of Pediatrics , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.affiliation: b Department of Environmental and Occupational Health , College of Public Health, University of Arkansas for Medical Sciences , Little Rock , AR , USA .
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.affiliation: a Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health , Boston , MA , USA .
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
mesh_terms: D000818:Animals; D002460:Cell Line; D003300:Copper / Q000633:toxicity*; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000633:toxicity*
chemical_list: D003300:Copper; C030973:cupric oxide
keywords: Copper oxide; DNA methylation; epigenetics; printer-emitted engineered nanoparticles; transposable elements