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Oxidative stress, DNA methylation, and telomere length changes in peripheral blood mononuclear cells after pulmonary exposure to metal-rich welding nanoparticles
NanoImpact ( IF 4.9 ) Pub Date : 2017-01-01 , DOI: 10.1016/j.impact.2017.01.001
Mohammad Shoeb 1 , Vamsi K Kodali 1 , Breanne Y Farris 1 , Lindsey M Bishop 1 , Terence G Meighan 1 , Rebecca Salmen 1 , Tracy Eye 1 , Sherri Friend 1 , Diane Schwegler-Berry 1 , Jenny R Roberts 1 , Patti C Zeidler-Erdely 1 , Aaron Erdely 1 , James M Antonini 1
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Welding fume is a complex mixture of different potentially cytotoxic and genotoxic metals, such as chromium (Cr), manganese (Mn), nickel (Ni), and iron (Fe). Documented health effects have been observed in workers exposed to welding fume. The objective of the study was to use an animal model to identify potential biomarkers of epigenetic changes (e.g., changes in telomere length, DNA methylation) in isolated peripheral blood mononuclear cells (PBMCs) after exposure to different welding fumes. Male Sprague-Dawley rats were exposed by intratracheal instillation (ITI) of 2.0 mg/rat of gas metal arc-mild steel (GMA-MS) or manual metal arc-stainless steel (MMA-SS) welding fume. Vehicle controls received sterile saline by ITI. At 4 h, 14 h, 1 d, 3 d, 10 d, and 30 d, bronchoalveolar lavage (BAL) was performed to assess lung inflammation. Whole blood was collected, and PBMCs were isolated. Dihydroethidium (DHE) fluorescence and 4-hydroxylnonenal protein adduct (P-HNE) formation were measured in PBMCs to assess reactive oxygen species (ROS) production. DNA alterations in PBMCs were determined by evaluating changes in DNA methylation and telomere length. Metal composition of the two fumes was different: MMA-SS (41 % Fe, 29 % Cr, 17 % Mn, 3 % Ni) versus GMA-MS (85 % Fe, 14 % Mn). The more soluble and chemically complex MMA-SS sample induced a more persistent and greater inflammatory response compared to the other groups. Also, oxidative stress markers increased at 24 h in the PBMCs recovered from the MMA-SS group compared to other group. No significant differences were observed when comparing DNA methylation between the welding fume and control groups at any of the time points, whereas the MMA-SS sample significantly increased telomere length at 1 and 30 d after a single exposure compared to the other groups. These findings suggest that genotoxic metals in MMA-SS fume (e.g., Cr and Ni), that are absent in the GMA-MS fume, may enhance lung toxicity, as well as induce markers of oxidative stress and increase telomere length in PBMCs. Importantly, the measurement of telomere length in cells isolated from peripheral blood may serve as a potential biomarker of response in the assessment of toxicity associated with welding fumes.

中文翻译:

肺暴露于富金属焊接纳米粒子后外周血单核细胞的氧化应激、DNA 甲基化和端粒长度变化

焊接烟尘是不同潜在细胞毒性和基因毒性金属的复杂混合物,例如铬 (Cr)、锰 (Mn)、镍 (Ni) 和铁 (Fe)。在暴露于焊接烟尘的工人中观察到有记录的健康影响。该研究的目的是使用动物模型来鉴定暴露于不同焊接烟雾后分离的外周血单核细胞 (PBMC) 中表观遗传变化(例如,端粒长度的变化、DNA 甲基化)的潜在生物标志物。雄性 Sprague-Dawley 大鼠通过气管内滴注 (ITI) 2.0 毫克/大鼠的气体金属电弧-低碳钢 (GMA-MS) 或手工金属电弧-不锈钢 (MMA-SS) 焊接烟雾暴露。媒介物对照由ITI接受无菌盐水。在 4 h、14 h、1 d、3 d、10 d 和 30 d 时,进行支气管肺泡灌洗 (BAL) 以评估肺部炎症。收集全血并分离PBMC。在 PBMC 中测量二氢乙锭 (DHE) 荧光和 4-羟基壬烯醛蛋白加合物 (P-HNE) 的形成,以评估活性氧 (ROS) 的产生。PBMC 中的 DNA 改变是通过评估 DNA 甲基化和端粒长度的变化来确定的。两种烟气的金属成分不同:MMA-SS(41% Fe、29% Cr、17% Mn、3% Ni)与 GMA-MS(85% Fe、14% Mn)。与其他组相比,更易溶解和化学复杂的 MMA-SS 样品诱导了更持久和更大的炎症反应。此外,与其他组相比,从 MMA-SS 组恢复的 PBMC 中的氧化应激标志物在 24 小时时增加。在任何时间点比较焊接烟雾和对照组之间的 DNA 甲基化时,均未观察到显着差异,而与其他组相比,MMA-SS 样品在单次暴露后 1 天和 30 天时显着增加了端粒长度。这些发现表明 MMA-SS 烟气中的基因毒性金属(例如,Cr 和 Ni),在 GMA-MS 烟气中不存在,可能会增强肺毒性,并诱导氧化应激标志物并增加 PBMC 中的端粒长度。重要的是,从外周血中分离出的细胞中端粒长度的测量可作为潜在的反应生物标志物,用于评估与焊接烟雾相关的毒性。以及诱导氧化应激标志物并增加 PBMC 中的端粒长度。重要的是,从外周血中分离出的细胞中端粒长度的测量可作为潜在的反应生物标志物,用于评估与焊接烟雾相关的毒性。以及诱导氧化应激标志物并增加 PBMC 中的端粒长度。重要的是,从外周血中分离出的细胞中端粒长度的测量可作为潜在的反应生物标志物,用于评估与焊接烟雾相关的毒性。
更新日期:2017-01-01
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