Rapid DNA Methylation Changes after Exposure to Traffic Particles

Abstract

Rationale: Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis. Objectives: We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. Methods: We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction-pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter < 2.5 mm [PM 2.5 ], or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (b) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure. Measurements and Main Results: Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (b 5 20.11; 95% confidence interval [CI], 20.18 to 20.04; P 5 0.002) and PM 2.5 (b 5 20.13; 95% CI, 20.19 to 20.06; P , 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (b 5 20.09; 95% CI, 20.17 to 20.01; P 5 0.03). No association was found with Alu methylation (P . 0.12). Conclusions: We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined.

Differential DNA methylation and PM2.5 species in a 450K epigenome-wide association study

“…6 Baccarelli et al 41 found decreased LINE-1 methylation in association with 7-day moving average black carbon and PM 2.5 levels, whereas no association was observed for Alu methylation. A controlled human exposure experiment observed hypomethylation of Alu and the toll-like receptor 4 (TLR4) gene among 15 healthy adults exposed to fine concentrated ambient particles (CAPs) for 130 min.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…In this sense, particulate air pollution has been associated with increased cardiovascular events, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity . Lower blood DNA methylation has been also found after exposure to traffic particles (Baccarelli et al, 2009) and after prolonged exposure to black carbon and SO 4 particles (Madrigano et al, 2011). Other toxics associated with carcinogenesis, including asbestos, alcohol, radiation and arsenic, are known to act also by epigenetic mechanisms (Christensen and Marsit, 2011).…”

Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries

“…CGIs were considered to be hypermethylated if the Alexa647/Alexa555 ratio was >3, corresponding to log 2 r/g >1. 6. Intermediate values were considered as partial hypo-or hypermethylation (Fig.…”

“…Furthermore, human and animal studies consistently indicate that global DNA hypomethylation accompanies advanced atherosclerosis (3,4). Importantly, 2 recent human studies have indicated that circulating levels of inflammation markers and exposure to environmental risk factors for atherosclerosis were associated with hypomethylation of highly repeated elements of leukocyte DNA (5,6). Identifying the sequences undergoing demethylation in atherosclerosis could provide important insights into the molecular mechanisms of atherogenesis and possibly of diet-or environment-gene interactions (7).…”