TY - JOUR
T1 - Particulate matter air pollution induces hypermethylation of the p16 promoter Via a mitochondrial ROS-JNK-DNMT1 pathway
AU - Soberanes, Saul
AU - Gonzalez, Angel
AU - Urich, Daniela
AU - Chiarella, Sergio E.
AU - Radigan, Kathryn A.
AU - Osornio-Vargas, Alvaro
AU - Joseph, Joy
AU - Kalyanaraman, Balaraman
AU - Ridge, Karen M.
AU - Chandel, Navdeep S.
AU - Mutlu, Gökhan M.
AU - De Vizcaya-Ruiz, Andrea
AU - Budinger, G. R Scott
N1 - Funding Information:
This work was supported by National Institute of Health ES015024, ES013995, HL071643, HL092963 and Training Grant T32HL076139, the Northwestern University Clinical and Translational Sciences Institute (NUCATS) Center for Translational Innovation (CTI) Pilot Award (UL1 RR025741 from the National Center for Research Resources (NCCR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research), The Veterans Administration and the American Lung Association.
PY - 2012
Y1 - 2012
N2 - Exposure of human populations to chronically elevated levels of ambient particulate matter air pollution < 2.5 mm in diameter (PM 2.5) has been associated with an increase in lung cancer incidence. Over 70% of lung cancer cell lines exhibit promoter methylation of the tumor suppressor p16, an epigenetic modification that reduces its expression.Weexposed mice to concentrated ambientPM 2.5 via inhalation, 8 hours daily for 3 weeks and exposed primary murine alveolar epithelial cells to daily doses of fine urban PM (5 μg/cm 2). In both mice and alveolar epithelial cells, PM exposure increased ROS production, expression of the DNA methyltransferase 1 (DNMT1), and methylation of the p16 promoter. In alveolar epithelial cells, increased transcription of DNMT1 and methylation of the p16 promoter were inhibited by a mitochondrially targeted antioxidant and a JNK inhibitor. These findings provide a potential mechanism by which PM exposure increases the risk of lung cancer.
AB - Exposure of human populations to chronically elevated levels of ambient particulate matter air pollution < 2.5 mm in diameter (PM 2.5) has been associated with an increase in lung cancer incidence. Over 70% of lung cancer cell lines exhibit promoter methylation of the tumor suppressor p16, an epigenetic modification that reduces its expression.Weexposed mice to concentrated ambientPM 2.5 via inhalation, 8 hours daily for 3 weeks and exposed primary murine alveolar epithelial cells to daily doses of fine urban PM (5 μg/cm 2). In both mice and alveolar epithelial cells, PM exposure increased ROS production, expression of the DNA methyltransferase 1 (DNMT1), and methylation of the p16 promoter. In alveolar epithelial cells, increased transcription of DNMT1 and methylation of the p16 promoter were inhibited by a mitochondrially targeted antioxidant and a JNK inhibitor. These findings provide a potential mechanism by which PM exposure increases the risk of lung cancer.
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U2 - 10.1038/srep00275
DO - 10.1038/srep00275
M3 - Article
C2 - 22355787
AN - SCOPUS:84859771300
SN - 2045-2322
VL - 2
JO - Scientific Reports
JF - Scientific Reports
M1 - 275
ER -
