Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel.
Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel.
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DOI：
10.1289/ehp.1104140
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发表时间：
2012-02
影响因子：
10.4
通讯作者：
Costa M
中科院分区：
文献类型：
--
作者：
Arita A;Niu J;Qu Q;Zhao N;Ruan Y;Nadas A;Chervona Y;Wu F;Sun H;Hayes RB;Costa M
背景：职业性镍暴露与肺癌和鼻癌的风险增加有关。镍化合物表现出弱的诱变活性，引起基因扩增，并破坏细胞的表观遗传动态平衡。然而，镍诱导的全球组蛋白修饰水平的变化只在体外进行了测试。目的：这项研究是在中国人群中进行的，目的是确定职业性镍暴露是否与全球组蛋白修饰水平的改变有关，并评估全球组蛋白修饰水平的个体间和个体内差异。方法：入选45名职业性镍接触者和75名参照者。检测受试者外周血单个核细胞(PBMC)中尿镍和总H3K4三甲基化、H3K9乙酰化和H3K9二甲基化水平。结果：镍接触组H3K4me3升高(0.25%±0.11%)，显著低于对照组(0.15%±0.04%；p=0.0004)，H3K9me2降低(0.11%±0.05%；对照组0.15%±0.04%，p=0.003)。H3K4me3与尿镍呈正相关(r=0.0008.4，p=0.0 1)，H3K9ac与尿镍呈负相关(r=0.1，p=0.0 1)。在两个暴露测试组中，H3K4me3、H3K9ac和H3K9me2的个体间变异大于个体内变异，导致可靠性系数(一组测量的一致性估计)对于镍暴露受试者分别为0.60、0.67和0.79，对于参照受试者分别为0.75、0.74和0.97。结论：本研究结果表明，职业性镍暴露与整体组蛋白修饰水平的改变有关，并且随着时间的推移，组蛋白修饰整体水平的测量相对稳定。
Background: Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro. Objective: This study was conducted in a Chinese population to determine whether occupational exposure to Ni is associated with alterations of global histone modification levels and to evaluate the inter- and intraindividual variance of global histone modification levels. Method: Forty-five subjects with occupational exposure to Ni and 75 referents were recruited. Urinary Ni and global H3K4 trimethylation, H3K9 acetylation, and H3K9 dimethylation levels were measured in peripheral blood mononuclear cells (PBMCs) of subjects. Results: H3K4me3 was elevated in Ni-exposed subjects (0.25% ± 0.11%) compared with referents (0.15% ± 0.04%; p = 0.0004), and H3K9me2 was decreased (Ni-exposed subjects, 0.11% ± 0.05%; referents, 0.15% ± 0.04%; p = 0.003). H3K4me3 was positively (r = 0.4, p = 0.0008) and H3K9ac was negatively (r = 0.1, p = 0.01) associated with urinary Ni. Interindividual variances of H3K4me3, H3K9ac, and H3K9me2 were larger compared with intraindividual variance in both exposure test groups, resulting in reliability coefficients (an estimate of consistency of a set of measurements) of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2, respectively, for Ni-exposed subjects and of 0.75, 0.74, and 0.97, respectively, for referent subjects. Conclusion: The results of this study indicate that occupational exposure to Ni is associated with alterations of global histone modification levels and that measurements of global levels of histone modifications are relatively stable over time in human PBMCs.
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影响因子：
64.8
作者：
Santos-Rosa, H;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
DOI：
10.1007/pl00007940
发表时间：
2000-01-01
影响因子：
3
作者：
Oliveira, JP;de Siqueira, MEPB;da Silva, CS
通讯作者：
da Silva, CS
影响因子：
30.8
作者：
Tamaru, H;Zhang, X;Selker, EU
通讯作者：
Selker, EU
DOI：
10.1073/pnas.51.5.786
发表时间：
1964-01-01
影响因子：
11.1
作者：
ALLFREY, VG;FAULKNER, R;MIRSKY, AE
通讯作者：
MIRSKY, AE
影响因子：
2.6
作者：
Hu, Yu;Li, Gang;Qu, Qingshan
通讯作者：
Qu, Qingshan