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Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Short-term exposure to engineered nanomaterials affects cellular epigenome.

Xiaoyan Lu1, Isabelle R Miousse2, Sandra V Pirela1

  • 1a Center for Nanotechnology and Nanotoxicology , Department of Environmental Health , Harvard School of Public Health , Boston , MA , USA .

Nanotoxicology
|May 5, 2015
PubMed
Summary

Engineered nanomaterials (ENMs) can alter the cellular epigenome, affecting DNA methylation and gene expression even at low, non-cytotoxic doses. This epigenetic impact is crucial for understanding ENM health risks.

Keywords:
DNA methylationengineered nanomaterialsepigeneticsprinter-emitted particlestransposable elements

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Area of Science:

  • Environmental Health
  • Toxicology
  • Epigenetics

Background:

  • Engineered nanomaterials (ENMs) are increasingly used, raising concerns about potential health risks.
  • While genotoxicity and cytotoxicity of ENMs are studied, their impact on the epigenome is largely unknown.
  • Understanding ENM effects on the epigenome is vital for assessing low-dose exposure risks.

Purpose of the Study:

  • To investigate if industry-relevant ENMs can impact the cellular epigenome at low, non-cytotoxic doses.
  • To assess epigenetic alterations including DNA methylation and gene expression of key genomic elements.
  • To evaluate these effects in relevant human and murine cell models.

Main Methods:

  • Exposure of human macrophages (THP-1), murine macrophages (RAW264.7), and human small airway epithelial cells (SAEC) to various ENMs (PEPs, MS-WF, CuO, TiO2).
  • Assessment of cytotoxicity, oxidative stress, and inflammatory responses with in vitro dosimetry.
  • Analysis of global DNA methylation, transposable element (TE) methylation (LINE-1, Alu/SINE), and expression of DNA methylation machinery and TEs.

Main Results:

  • ENM-induced cytotoxicity was low (0-15%) across cell lines.
  • Oxidative stress was observed in specific cell-ENM combinations (SAEC-PEPs, THP-1-CuO).
  • ENMs induced modest alterations in LINE-1 and Alu/SINE DNA methylation, reactivated TEs, and decreased DNA methylation machinery expression.

Conclusions:

  • Environmentally relevant concentrations of ENMs can affect the cellular epigenome.
  • Epigenetic changes occur independently of significant cytotoxic effects.
  • Findings highlight the need to consider epigenetic modifications in ENM risk assessment.