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

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

Published In Sci Rep, (2012)

Abstract: Exposure of human populations to chronically elevated levels of ambient particulate matter air pollution < 2.5 μm 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. We exposed mice to concentrated ambient PM(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.

PubMed ID: 22355787 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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