Short-term exposure to engineered nanomaterials affects cellular epigenome.
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.
a Center for Nanotechnology and Nanotoxicology , Department of Environmental Health , Harvard School of Public Health , Boston , MA , USA .
Xiaoyan
X
Lu
b Department of Environmental and Occupational Health , College of Public Health, University of Arkansas for Medical Sciences , Little Rock , AR , USA , and.
Isabelle R
IR
Miousse
a Center for Nanotechnology and Nanotoxicology , Department of Environmental Health , Harvard School of Public Health , Boston , MA , USA .
Sandra V
SV
Pirela
c Department of Pediatrics , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
Stepan
S
Melnyk
b Department of Environmental and Occupational Health , College of Public Health, University of Arkansas for Medical Sciences , Little Rock , AR , USA , and.
Igor
I
Koturbash
a Center for Nanotechnology and Nanotoxicology , Department of Environmental Health , Harvard School of Public Health , Boston , MA , USA .
Philip
P
Demokritou
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004251:DNA Transposable Elements / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D013232:Steel / Q000633:toxicity; D014025:Titanium / Q000737:chemistry / Q000633:toxicity; D014896:Welding
D016207:Cytokines; D004251:DNA Transposable Elements; D013232:Steel; C009495:titanium dioxide; D003300:Copper; D014025:Titanium; C000520:cuprous oxide
DNA methylation; engineered nanomaterials; epigenetics; printer-emitted particles; transposable elements