Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study

Background: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications.

Methods: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM₁₀ (both day-of and 14-day average exposures), personal PM_2.5, black carbon (BC), and elemental components (potassium, sulfur, iron, silicon, aluminum, zinc, calcium, and titanium). For both PM₁₀ measures, we obtained hourly ambient PM₁₀ data for the study period from the Beijing Municipal Environmental Bureau's 27 representatively distributed monitoring stations. We then calculated a 24h average for each examination day and a moving average of ambient PM₁₀ measured in the 14 days prior to each examination. Examinations measured global levels of H3 lysine 9 acetylation (H3K9ac), H3 lysine 9 tri-methylation (H3K9me3), H3 lysine 27 tri-methylation (H3K27me3), and H3 lysine 36 tri-methylation (H3K36me3) in blood leukocytes collected after work. We used adjusted linear mixed-effect models to examine percent changes in histone modifications per each μg/m³ increase in PM exposure.

Results: In all participants each μg/m³ increase in 14-day average ambient PM₁₀ exposure was associated with lower H3K27me3 (β=-1.1%, 95% CI: -1.6, -0.6) and H3K36me3 levels (β=-0.8%, 95% CI: -1.4, -0.1). Occupation-stratified analyses showed associations between BC and both H3K9ac and H3K36me3 that were stronger in office workers (β=4.6%, 95% CI: 0.9, 8.4; and β=4.1%, 95% CI: 1.3; 7.0 respectively) than in truck drivers (β=0.1%, 95% CI: -1.3, 1.5; and β=0.9%, 95% CI: -0.9, 2.7, respectively; both p_interaction <0.05). Sex-stratified analyses showed associations between examination-day PM₁₀ and H3K9ac, and between BC and H3K9me3, were stronger in women (β=10.7%, 95% CI: 5.4, 16.2; and β=7.5%, 95% CI: 1.2, 14.2, respectively) than in men (β=1.4%, 95% CI: -0.9, 3.7; and β=0.9%, 95% CI: -0.9, 2.7, respectively; both p_interaction <0.05). We observed no associations between personal PM_2.5 or elemental components and histone modifications.

Conclusions: Our results suggest a possible role of global histone H3 modifications in effects of traffic-derived PM exposures, particularly BC exposure. Future studies should assess the roles of these modifications in human diseases and as potential mediators of air pollution-induced disease, in particular BC exposure.