Short-term exposure to engineered nanomaterials affects cellular epigenome

Abstract

Extensive incorporation of engineered nanomaterials (ENMs) into industrial and biomedical applications increases the risks of exposure to these potentially hazardous materials. While the geno- and cytotoxic effects of ENMs have been investigated, the potential of ENMs to target the cellular epigenome remains largely unknown. Our goal was to determine whether industry relevant ENMs can affect the epigenome at low cytotoxic doses. A panel of cells relevant to inhalation exposures such as human and murine macrophages (THP-1 and RAW264.7, respectively) and human small airway epithelial cells (SAEC) were exposed to printer-emitted engineered nanoparticles (PEPs), mild steel welding fumes (MS-WF), copper oxide (CuO) and titanium dioxide nanoparticles. Toxicological effects, including cytotoxicity, oxidative stress and inflammatory responses were assessed, taking into consideration in vitro dosimetry. The effects of ENMs on cellular epigenome were determined by addressing the global and transposable elements (TEs)-associated DNA methylation and expression of DNA methylation machinery and TEs. The percentage of ENMs-induced cytotoxicity for all cell lines was in the range of 0–15%. Oxidative stress was evident in SAEC after exposure to PEPs and in THP-1 when exposed to CuO. In addition, exposure to ENMs resulted in modest alterations in DNA methylation of two most abundant TEs in mammalian genomes, LINE-1 and Alu/SINE, their transcriptional reactivation, and decreased expression of DNA methylation machinery in a cell-, dose- and ENM-dependent manner. These results indicate that exposure to ENMs at environmentally relevant concentrations, aside from the geno- and cytotoxic effects, can also affect the epigenome of target cells.

• DNA methylation
• engineered nanomaterials
• epigenetics
• printer-emitted particles
• transposable elements

Acknowledgements

We would like to thank Dilpreet Singh for his assistance in TEM analysis, Oleksandra Pavliv for her assistance with DNA methylation analysis, Dr. Andrea Baccarelli and Jia Zhong for their help in reviewing the epigenetic results. We are thankful to Dr. Rebecca Helm for editing the manuscript.

Declaration of interest

This work was supported by the funding from NIEHS Center (Grant# ES-000002), NIOSH, CPSC (Grant # 212-2012-M-51174), NIH UL1TR000039 and KL2TR000063, and the Arkansas Biosciences Institute. The authors report no competing financial interests. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Tables 1-5 and Figures 1-7.