In vitro toxicity and epigenotoxicity of different types of ambient particulate matter

Isabelle R. Miousse, Marie Cecile G. Chalbot, Rupak Pathak, Xiaoyan Lu, Etienne Nzabarushimana, Kimberly Krager, Nukhet Aykin-Burns, Martin Hauer-Jensen, Philip Demokritou, Ilias G. Kavouras, Igor Koturbash

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-μg/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.

Original languageEnglish (US)
Pages (from-to)473-487
Number of pages15
JournalToxicological Sciences
Volume148
Issue number2
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology

Keywords

  • Ambient particulate matter
  • Chromosomal aberrations
  • DNA methylation
  • Satellite DNA
  • Transposable elements

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