Inhalable Metal-Rich Air Particles and Histone H3K4 Dimethylation and H3K9 Acetylation in a Cross-sectional Study of Steel Workers

被引：114

作者：

Cantone, Laura ^{[2
,3
,4
]}

Nordio, Francesco ^{[2
,3
,4
,5
]}

Hou, Lifang ^{[6
]}

Apostoli, Pietro ^{[7
]}

Bonzini, Matteo ^{[8
]}

Tarantini, Letizia ^{[2
,3
,4
]}

Angelici, Laura ^{[2
,3
,4
]}

Bollati, Valentina ^{[2
,3
,4
]}

Zanobetti, Antonella ^{[1
]}

Schwartz, Joel ^{[1
]}

Bertazzi, Pier A. ^{[2
,3
,4
]}

Baccarelli, Andrea ^{[1
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program,Lab Environm Ep, Boston, MA 02215 USA

[2] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy

[3] Ist Ricovero & Cura Carattere Sci, Milan, Italy

[4] Maggiore Hosp, Mangiagalli & Regina Elena Fdn, Milan, Italy

[5] Univ Parma, Sch Med, Dept Clin Med Nephrol & Hlth Sci, I-43100 Parma, Italy

[6] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA

[7] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy

[8] Univ Insubria, Dept Clin & Biol Sci, Varese, Italy

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2011年 / 119卷 / 07期

关键词：

environmental carcinogens; epigenetics; histone modifications; metals; particulate matter; CONCENTRATED AMBIENT PARTICLES; HEART-RATE-VARIABILITY; PARTICULATE MATTER; DNA METHYLATION; LUNG-CANCER; OXIDATIVE STRESS; UTAH VALLEY; NICKEL; EXPOSURE; ASSOCIATION;

D O I：

10.1289/ehp.1002955

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

BACKGROUND: Epidemiology investigations have linked exposure to ambient and occupational air particulate matter (PM) with increased risk of lung cancer. PM contains carcinogenic and toxic metals, including arsenic and nickel, which have been shown in in vitro studies to induce histone modifications that activate gene expression by inducing open-chromatin states. Whether inhalation of metal components of PM induces histone modifications in human subjects is undetermined. OBJECTIVES: We investigated whether the metal components of PM determined activating histone modifications in 63 steel workers with well-characterized exposure to metal-rich PM. METHODS: We determined histone 3 lysine 4 dimethylation (H3K4me2) and histone 3 lysine 9 acetylation (H3K9ac) on histones from blood leukocytes. Exposure to inhalable metal components (aluminum, manganese, nickel, zinc, arsenic, lead, iron) and to total PM was estimated for each study subject. RESULTS: Both H3K4me2 and H3K9ac increased in association with years of employment in the plant (p-trend = 0.04 and 0.006, respectively). H3K4me2 increased in association with air levels of nickel [beta = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (beta = 0.16; 95% CI, 0.02-0.3), and iron (beta = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (beta = 0.24; 95% CI, -0.02 to 0.51), arsenic (beta = 0.21; 95% CI, -0.06 to 0.48), and iron (beta = 0.22; 95% CI, -0.03 to 0.47). Cumulative exposures to nickel and arsenic, defined as the product of years of employment by metal air levels, were positively correlated with both H3K4me2 (nickel: beta = 0.16; 95% CI, 0.01-0.3; arsenic: beta = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: beta = 0.27; 95% CI, 0.01-0.54; arsenic: beta = 0.28; 95% CI, 0.04-0.51). CONCLUSIONS: Our results indicate histone modifications as a novel epigenetic mechanism induced in human subjects by long-term exposure to inhalable nickel and arsenic.

引用

页码：964 / 969

页数：6

共 49 条

[21] Inflammatory lung injury after bronchial instillation of air pollution particles [J].