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Between strain and tissue differences exist in global hydroxymethylation after acute ozone exposure.
Citation:
Miller, C., M. Schladweiler, J. Dye, M. Hazari, U. Kodavanti, AND Ian Gilmour. Between strain and tissue differences exist in global hydroxymethylation after acute ozone exposure. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
Our study provides the first causal evidence that an inhaled pollutant induces systemic changes to 5hmC levels in both a tissue and strain-dependent manner.
Description:
Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression with both normal physiologic function as well as disease states. Demethylation of cysteine residues, generally leading to gene activation, is an oxygen-dependent reaction and creates the semi-stable intermediate 5-hydroxymethyl cytosine (5hmC). As air pollutants, in particular ozone, produce a strong oxidative stress response, it has been hypothesized that changes in 5hmC will occur not only in response to ozone but may also provide a novel biosensor of exposure. In the current study 12 week old, male Long-Evans and Wistar Kyoto (WKY) rats (n=32) were exposed to 6 hours of whole-body 1.0 ppm ozone or air and immediately euthanized. Global 5hmC levels were determined using an ELISA. Both WKY and Long-Evans exposed to ozone increased hydroxymethylation within the liver compared to air controls (p<0.05). In adipose tissue, an acute ozone exposure resulted in global reductions in 5hmC within both strains compared to their air controls (p<0.06). A strain difference became apparent in the response within the lung. Long-Evans rats increased global 5hmC levels in the lung compared to controls, with no difference measured in the WKY rats. Previous work has shown that relative to many other strains, ozone increases bronchoconstriction and vitamin C sequestration in the WKY strain. These findings suggest that total ozone dose and oxidative damage may be reduced in WKY rats. Our study provides the first causal evidence that an inhaled pollutant induces systemic changes to 5hmC levels in both a tissue and strain-dependent manner. Further, we suggest strain differences may be due to differing antioxidant defense systems within the lung. Lastly, we recommend that researchers adopt a broad approach to tissue screens when considering 5hmC as a biomarker of exposure due to the inherent differences we measured. This abstract does not reflect US EPA policy.