Real-world PM2.5 exposure induces pathological injury and DNA damage associated with miRNAs and DNA methylation alteration in rat lungs

Lifang Zhao, Mei Zhang, Lirong Zhao, Yufei Zhao, Zongwei CAI, Kin Lam YUNG, Dong Chuan*, Ruijin Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Fine particulate matter (PM2.5) has been demonstrated to threaten public health and increase lung cancer risk. DNA damage is involved in the pathogenesis of lung cancer. However, the mechanisms of epigenetic modification of lung DNA damage are still unclear. This study developed a real-world air PM2.5 inhalation system and exposed rats for 1 and 2 months, respectively, and investigated rat lungs pathological changes, inflammation, oxidative stress, and DNA damage effects. OGG1 and MTH1 expression was measured, along with their DNA methylation status and related miRNAs expression. The results showed that PM2.5 exposure led to pathological injury, influenced levels of inflammatory cytokines and oxidative stress factors in rat lungs. Of note, 2-month PM2.5 exposure aggravated pathological injury. Besides, PM2.5 significantly elevated OGG1 expression and suppressed MTH1 expression, which was correlated to oxidative stress and partially mediated by reducing OGG1 DNA methylation status and increasing miRNAs expression related to MTH1 in DNA damage with increases of γ-H2AX, 8-OHdG and GADD153. PM2.5 also activated c-fos and c-jun levels and inactivated PTEN levels in rat lungs. These suggested that epigenetic modification was probably a potential mechanism by which PM2.5-induced genotoxicity in rat lungs.
Original languageEnglish
Pages (from-to)28788-28803
Number of pages16
JournalEnvironmental Science and Pollution Research
Volume29
Issue number19
Early online date6 Jan 2022
DOIs
Publication statusPublished - Apr 2022

Scopus Subject Areas

  • Environmental Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pollution
  • Health, Toxicology and Mutagenesis
  • Environmental Chemistry

User-Defined Keywords

  • DNA damage
  • DNA methylation
  • Pathological injury
  • Rats
  • Real-world PM2.5 exposure
  • miRNAs
  • Real-world PM exposure

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