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.

• Copper oxide
• DNA methylation
• epigenetics
• printer-emitted engineered nanoparticles
• transposable elements

Acknowledgements

We would like to thank Oleksandra Pavliv for her assistance with the DNA methylation analysis and Dr. Rebecca Helm for editing the manuscript.

Declaration of interest

This work was supported by the funding from NIEHS grant (grant number ES-000002), NIOSH/CPSC (grant number 212-2012-M-51174), NIH 1P20GM109005, UL1TR000039 and KL2TR000063, and the Arkansas Biosciences Institute. Dr. Pirela was supported by NIH training grant (grant number HL007118). The authors alone are responsible for the content and writing of the paper and report no competing financial interests.

Supplementary material available online.

Supplementary Tables 1-4