Effects of Exposure to Metal-Rich Air Particles on DNA Methylation

Abstract

ISEE-0225 Background and Objective: Air particles and their metal components induce aberrant gene expression related to their systemic effects, including cardiorespiratory disease and lung cancer. The mechanisms determining particle-related gene deregulation are largely undetermined. In foundry workers with well-characterized exposure to airborne metal-rich particles, we evaluated promoter DNA methylation, a major epigenetic mechanism for expression inhibition, in ten cardiorespiratory and cancer genes. Methods: We measured DNA methylation (expressed as %5-methylcytosine) by PCR-Pyrosequencing on blood DNA from 63 foundry workers on the first day of a workweek (following two days off) and after three days of work (post-exposure). Personal exposures to particulate matter with diameter <10 μm (PM10) or <1 μm (PM1), and their metal components (Cr, Cd, As, Pb, Mn, Ni) were estimated using area-specific measurements. Results: Post-exposure samples exhibited a significant increase in methylation of APC (difference = 0.24, P = 0.005) and p16 (difference = 0.14, P = 0.006), and a decrease in Rassf1A (difference = −1.09; P < 0.001), CDH13 (difference = −0.61; P = 0.001), TNFα (difference = −0.35; P = 0.005), and IFNγ (difference = −0.86; P < 0.001). No differences were found in p53, Il-6, eNOS, and Et1. In post-exposure samples, APC methylation was associated with PM10 (β = 0.65; P < 0.001) and PM1 (β = 0.75; P = 0.002) exposure; Rassf1A methylation with Cr (β = −2.59; P = 0.03), Pb (β = −3.44; P = 0.005), and Cd (β = −2.68; P = 0.01); CDH13 methylation with Cd (β = −2.90; P = 0.02). TNFα methylation was borderline associated with Ni (β = −1.65; P = 0.07) and Mn (β = -0.65; P = 0.06). IFNγ methylation did not show any consistent association with exposure levels. Some of the exposures were associated with methylation in both pre- and post-exposure samples, possibly reflecting effects operating over an extended timeframe. Et1 methylation was associated with Pb (β = −3.03; P = 0.005) and Cd (β = −2.46; P = 0.01), eNOS with PM10 (β-0.71; P = 0.03), Cr (β = −1.37; P = 0.01), Pb (β = −1.20; P = 0.04) and Cd (β = -1.41 P = 0.004). Conclusions: Metal-rich air particles modify the DNA methylation of genes related to cardiorespiratory and cancer outcomes.