Particulate Matter Air Pollution Induces Hypermethylation of the p16 Promoter Via a Mitochondrial ROS-JNK-DNMT1 Pathway

From: http://www.nature.com/srep/2012/120217/srep00275/full/srep00275.html

Nature

Scientific Reports 2, Article number: 275 doi:10.1038/srep00275 Received 23 September 2011; Accepted 20 January 2012; Published 17 February 2012

Particulate matter Air Pollution induces hypermethylation of the p16 promoter Via a mitochondrial ROS-JNK-DNMT1 pathway

Saul Soberanes, Angel Gonzalez, Daniela Urich, Sergio E. Chiarella, Kathryn A. Radigan, Alvaro Osornio-Vargas, Joy Joseph, Balaraman Kalyanaraman, Karen M. Ridge, Navdeep S. Chandel, Gökhan M. Mutlu, Andrea De Vizcaya-Ruiz & G. R. Scott Budinger

The authors provide a background for their study: “Exposure of human populations to chronically elevated levels of ambient particulate matter air pollution < 2.5 μm in diameter (PM2.5) 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.”

The results of the study were as follows: “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. “

The authors conclude, “These findings provide a potential mechanism by which PM exposure increases the risk of lung cancer.”

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