In vivoepigenetic 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 twofold: 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.

Toxicological implications of released particulate matter during thermal decomposition of nano-enabled thermoplastics

“…Nano-enabled thermoplastics or nanocomposites can contain nanofillers such as silica nanoparticles (Stojanović et al , 2013), clays (Fang et al , 2008), metal oxides (Perkgoz et al , 2011), carbon fibers (Al-Saleh et al , 2013) and carbon nanotubes (Sahoo et al , 2010) enabling extensive mechanical and electrical properties. Although, ENMs afford many useful properties, certain ENMs can cause adverse health effects such as cytotoxicity (DeLoid et al , 2016; DeLoid et al , 2014; Pirela et al , 2013; Pirela et al , 2014a), genotoxicity (Watson et al , 2013), epigenetic changes (Lu et al , 2016a; Lu et al , 2016b), and lung inflammation upon exposure (Borm et al , 2006; Konduru et al , 2014; Pirela, et al, 2013; Pirela et al , 2016). With this in mind, considerable concern over the hazards that may ensue due to the release of ENMs during consumer use and disposal of nano-enabled thermoplastics has created efforts to understand potential exposures across the life cycle of nano-enabled products (Bouillard et al , 2013; Grassian et al , 2016; Pirela et al , 2014b; Sisler et al , 2014; Wohlleben et al , 2011; Wohlleben and Neubauer, 2016).…”

“…Likewise, metal oxide ENMs such as iron oxide (Fe 2 O 3 ) and titanium (TiO 2 ) are currently utilized in a number of nano-enabled products to enhance optical (Li et al , 2010), antimicrobial (Palza, 2015), and magnetic (Novakova et al , 2003) properties among others. These same properties could elicit adverse effects in biological systems by inhibiting cellular and physiological processes (Larsen et al , 2016; Lu, et al, 2016a; Lu, et al, 2016b). Whether ENMs used in various NEPS can be released across the life cycle and pose human health hazards remains unclear due to the limited number of studies focusing on comprehensive life cycle environmental health and safety implications of NEPs.…”

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

“…Moreover, recent findings suggest that PEPs can also influence the cellular epigenome. Particularly, a 24-hour exposure to PEPs caused altered expression of DNA methylation machinery in small airway epithelial cells, in turn leading to changes in global DNA methylation and reactivation of transposable element (TE) LINE-1 and Alu (Pirela et al, 2015; Lu et al, 2015a). …”

“…In this study, we sought to further expand on the latest cellular toxicology studies performed by our group on PEPs (Sisler et al, 2014; Pirela et al, 2015; Lu et al, 2015b). Particularly, we present findings on the murine responses to intratracheal instillation exposures to various doses of PEPs.…”

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…, chemical reactivity, mechanical strength, digestibility, transport properties, and cellular uptake, accumulation, and distribution (Acosta, 2009; Buzea et al , 2007; Cohen et al , 2014a; Davidson et al , 2016; Konduru et al , 2015; Konduru et al , 2014; Konduru et al , 2016; Lu et al , 2016a; Lu et al , 2016b; Ma et al , 2015; Pirela et al , 2016a; Pirela et al , 2016b; Sisler et al , 2015; Sotiriou et al , 2014; Watson et al , 2014; Yokel et al , 2014; Zhou et al , 2014). These changes are associated with the smaller particle dimensions and higher surface areas of nanoparticles compared to larger particles, as well as to quantum effects taking place in the nanoscale (Pyrgiotakis et al , 2014; Pyrgiotakis et al , 2013).…”