可吸入富金属空气颗粒与组蛋白 H3K4 二甲基化和 H3K9 乙酰化在钢铁工人的横断面研究中的关系
Inhalable metal-rich air particles and histone H3K4 dimethylation and H3K9 acetylation in a cross-sectional study of steel workers.
机构信息
Department of Environmental and Occupational Health, Università di Milano and Istituto Di Ricovero e Cura a Carattere Scientifico, and Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy.
出版信息
Environ Health Perspect. 2011 Jul;119(7):964-9. doi: 10.1289/ehp.1002955. Epub 2011 Mar 8.
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 [β = 0.16; 95% confidence interval (CI), 0.03-0.3], arsenic (β = 0.16; 95% CI, 0.02-0.3), and iron (β = 0.14; 95% CI, 0.01-0.26). H3K9ac showed nonsignificant positive associations with air levels of nickel (β = 0.24; 95% CI, -0.02 to 0.51), arsenic (β = 0.21; 95% CI, -0.06 to 0.48), and iron (β = 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: β = 0.16; 95% CI, 0.01-0.3; arsenic: β = 0.16; 95% CI, 0.03-0.29) and H3K9ac (nickel: β = 0.27; 95% CI, 0.01-0.54; arsenic: β = 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.
背景
流行病学研究表明，暴露于环境和职业空气颗粒物（PM）与肺癌风险增加有关。PM 含有致癌和有毒金属，包括砷和镍，体外研究表明，这些金属会诱导组蛋白修饰，通过诱导开放染色质状态来激活基因表达。吸入 PM 中的金属成分是否会在人体中诱导组蛋白修饰尚不确定。
目的
我们研究了在 63 名具有明确富金属 PM 暴露史的钢铁工人中，PM 的金属成分是否会诱导组蛋白发生激活修饰。
方法
我们测定了血液白细胞中组蛋白的组蛋白 3 赖氨酸 4 二甲基化（H3K4me2）和组蛋白 3 赖氨酸 9 乙酰化（H3K9ac）。为每位研究对象估计了可吸入金属成分（铝、锰、镍、锌、砷、铅、铁）和总 PM 的暴露情况。
结果
在工厂工作年限与 H3K4me2 和 H3K9ac 均呈正相关（p-trend=0.04 和 0.006，分别）。H3K4me2 与空气中的镍[β=0.16；95%置信区间（CI），0.03-0.3]、砷（β=0.16；95% CI，0.02-0.3）和铁（β=0.14；95% CI，0.01-0.26）水平呈正相关。H3K9ac 与空气中的镍（β=0.24；95% CI，-0.02 至 0.51）、砷（β=0.21；95% CI，-0.06 至 0.48）和铁（β=0.22；95% CI，-0.03 至 0.47）水平呈正相关，但无统计学意义。镍和砷的累积暴露量，定义为工作年限与金属空气水平的乘积，与 H3K4me2（镍：β=0.16；95% CI，0.01-0.3；砷：β=0.16；95% CI，0.03-0.29）和 H3K9ac（镍：β=0.27；95% CI，0.01-0.54；砷：β=0.28；95% CI，0.04-0.51）均呈正相关。
结论
我们的结果表明，组蛋白修饰是一种新的表观遗传机制，可在人体中诱导长期吸入可吸入镍和砷。
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