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The early epigenetic response to ozone: impacts on DNA methylation and hydroxymethylation.
Schladweiler, M., J. Dye, M. Hazari, AND U. Kodavanti. The early epigenetic response to ozone: impacts on DNA methylation and hydroxymethylation. North Carolina Society of Toxicology, Durham, NC, October 25, 2016.
This study provides novel information on the epigenetic response immediately following ozone exposure in the lung.
Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating the direct epigenetic effects following exposure to ambient air pollution. Thus the purpose of this study was to investigate the early epigenetic response to ozone in comparison to the epigenetic modifier 5-aza-2'-deoxycytidine (5-Aza) in rats. 12 week old, male Long-Evans rats (n=16) were exposed to 4 hours of whole-body 1.0 ppm ozone or air and immediately euthanized. A subset of animals were additionally treated with 5-Aza (n=16) to serve as an epigenetic control to ozone exposure. Neither 5-Aza nor ozone by itself induced changes to the global methylome or hydroxmethylome of the lung measured by ELISA. Despite this finding, ozone exposure induced a significant increase in the activity of the DNA methyltransferase enzymes in the lung which was reversed with 5-Aza treatment. Interestingly, a significant interaction between 5-Aza treatment and ozone exposure was found in a large array of data. The interaction between 5-Aza and ozone produced indicators of pulmonary edema and elevated lung damage. Along with these adverse changes, expression of major epigenetic enzymes (Tet 1-3, Dnmt3 a-b) were found to be perturbed in both the lung and hepatic tissues. While ozone exposure appears to induce increases in DNA methyltransferase activity, the relationship between 5-Aza and ozone is a potentially clinically relevant finding. 5-Aza is an approved chemotherapeutic for the treatment of myelodysplastic syndromes. Therefore, evidence from this work may suggest that individuals receiving this drug may be at a unique risk to air pollution or additional lung irritants that has not been previously identified. This abstract does not reflect US EPA policy.
URLs/Downloads:NCSOT ABSTRACT CMILLER.DOCX
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH