TY - JOUR
T1 - Real-world PM2.5 exposure induces pathological injury and DNA damage associated with miRNAs and DNA methylation alteration in rat lungs
AU - Zhao, Lifang
AU - Zhang, Mei
AU - Zhao, Lirong
AU - Zhao, Yufei
AU - CAI, Zongwei
AU - YUNG, Kin Lam
AU - Chuan, Dong
AU - Li, Ruijin
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (91843301), Project on Social Development by the Shanxi Science and Technology Department (201903D321079), Nature Science Foundation of Shanxi Province in China (201801D121260), Training Program of Outstanding Achievement of Higher Education Institutions in Shanxi (2019KJ003), and Hundred Talents Program of Shanxi Province in China (2017-07).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - DNA damage
KW - DNA methylation
KW - Pathological injury
KW - Rats
KW - Real-world PM2.5 exposure
KW - miRNAs
KW - Real-world PM exposure
UR - http://www.scopus.com/inward/record.url?scp=85122279348&partnerID=8YFLogxK
U2 - 10.1007/s11356-021-17779-7
DO - 10.1007/s11356-021-17779-7
M3 - Journal article
SN - 0944-1344
VL - 29
SP - 28788
EP - 28803
JO - Environmental Science and Pollution Research
JF - Environmental Science and Pollution Research
IS - 19
ER -
