Evaluating the effect of ambient particulate pollution on DNA methylation in Alaskan sled dogs: Potential applications for a sentinel model of human health

Background: Exposure to ambient particulate matter (PM) is known to be associated with increased morbidity and mortality in human populations. During the winter months in Fairbanks, Alaska, severe temperature inversions lead to elevated concentrations of ambient PM smaller than 2.5 mu m (PM2.5). Sled dogs represent an easily accessible environmentally exposed population that may yield findings informative for human health risk assessment. Objectives: In this pilot study, we evaluated whether ambient PM was associated with markers of global methylation in sled dogs. Methods: Kennels were strategically recruited to provide a wide PM2.5 exposure gradient for the Fairbanks area. Continuous monitoring of ambient PM2.5 was conducted at each kennel during the winter of 2012/13 using a DustTrak 8530. Dogs received a physical examination and assessment of standard hematology and clinical chemistries. Global methylation was determined using the LUminometric Methylation Assay (LUMA) and 5-Methycytosine (5-mC) quantification. Results: Three sled dog kennels (n similar to 30 dogs/kennel) were evaluated and sampled. The average PM2.5 concentrations measured for kennels A, B, and C were 90 mu g/m(3), 48 mu g/m(3), 16 mu g/m(3) (p <0.0001), respectively. The average (standard deviation) global methylation percentage for each kennel measured by LUMA was 76.22 (1.85), 76.52 (1.82), and 76.72 (2.26), respectively. The average (standard deviation) global methylation percentage for each kennel measured by 5-mC was 0.16 (0.04), 0.15 (0.04), and 0.15 (0.05), respectively. There was no statistically significant difference between the three kennels and their average global methylation percentage either by LUMA or 5-mC. Conclusions: In this study we evaluated global methylation using LUMA and 5-mC and found no differences between kennels, though exposure to ambient PM2.5 was significantly different between kennels. As more information becomes available regarding immunologically-related canine genes and functionally active promoter subunits, the utility of this surrogate could increase. (C) 2014 Elsevier B.V. All rights reserved.