4.5 Article

In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter

Journal

TOXICOLOGICAL SCIENCES
Volume 148, Issue 2, Pages 473-487

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfv200

Keywords

chromosomal aberrations; DNA methylation; ambient particulate matter; satellite DNA; transposable elements

Categories

Funding

  1. National Institutes of Health Center of Biological Research Excellence [1P20GM109005-01A1]
  2. National Institutes of Health UAMS Clinical and Translational Science Award [UL1TR000039, KL2TR000063]
  3. National Institute for Occupational Safety and Health and Consumer Product Safety Commission [212-2012-M-51174]
  4. Arkansas Space Grant Consortium through National Aeronautics and Space Administration [NNX13AB29A]
  5. Arkansas Biosciences Institute

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Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in thein vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-mu g/ml doses of the water soluble extract of 6 types of PM: soil dust, road dust, agricultural dust, traffic exhausts, biomass burning, and pollen, collected in January-April of 2014 in the area of Little Rock, Arkansas. Cytotoxicity, oxidative potential, epigenetic endpoints, and chromosomal aberrations were addressed. Exposure to 6 types of PM resulted in induction of cytotoxicity and oxidative stress in a type-, time-, and dose-dependent manner. Epigenetic alterations were characterized by type-, time-, and dose-dependent decreases of DNA methylation/demethylation machinery, increased DNA methyltransferases enzymatic activity and protein levels, and transcriptional activation and subsequent silencing of transposable elements LINE-1, SINE B1/B2. The most pronounced changes were observed after exposure to soil dust that were also characterized by hypomethylation and reactivation of satellite DNA and structural chromosomal aberrations in the exposed cells. The results of our study indicate that the water-soluble fractions of the various types of PM have differential potential to target the cellular epigenome.

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