Epigenetic alterations induced by ambient particulate matter in mouse macrophages

Environ Mol Mutagen. 2014 Jun;55(5):428-35. doi: 10.1002/em.21855. Epub 2014 Feb 17.

Abstract

Respiratory mortality and morbidity has been associated with exposure to particulate matter (PM). Experimental evidence suggests involvement of cytotoxicity, oxidative stress, and inflammation in the development of PM-associated pathological states; however, the exact mechanisms remain unclear. In the current study, we analyzed short-term epigenetic response to PM10 (particles with aerodynamic diameter less than 10 μm) exposure in mouse ascitic RAW264.7 macrophages (BALB/C Abelson murine leukemia virus-induced tumor). Ambient PM10 was collected using a high volume sampler in Little Rock, AR. Analysis revealed that PM10 was composed mainly of Al and Fe, and the water soluble organic fraction was dominated by aliphatic and carbohydrate fragments and minor quantities of aromatic components. Exposure to PM10 compromised the cellular epigenome at concentrations 10-200 µg/ml. Specifically, epigenetic alterations were evident as changes in the methylation and expression of repetitive element-associated DNA and associated DNA methylation machinery. These results suggest that epigenetic alterations, in concert with cytotoxicity, oxidative stress, and inflammation, might contribute to the pathogenesis of PM-associated respiratory diseases.

Keywords: DNA methylation; air pollution; repetitive elements.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 5-Methylcytosine / analysis
  • Animals
  • Apoptosis / drug effects
  • Cells, Cultured
  • DNA Methylation / drug effects*
  • Epigenesis, Genetic / drug effects*
  • In Situ Nick-End Labeling
  • Inflammation / chemically induced*
  • L-Lactate Dehydrogenase / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Oxidative Stress / drug effects*
  • Particulate Matter / toxicity*
  • Repetitive Sequences, Nucleic Acid / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Particulate Matter
  • Tumor Necrosis Factor-alpha
  • 5-Methylcytosine
  • L-Lactate Dehydrogenase