Department of Pharmaceutical Sciences, College of Pharmacy, The University of New Mexico, Albuquerque, New Mexico 87131, USA.
College of Nursing, The University of New Mexico, Albuquerque, New Mexico 87131, USA.
Toxicol Sci. 2021 Nov 24;184(2):286-299. doi: 10.1093/toxsci/kfab109.
Inhalation of tungsten particulates is a relevant route of exposure in occupational and military settings. Exposure to tungsten alloys is associated with increased incidence of lung pathologies, including interstitial lung disease and cancer. We have demonstrated, oral exposure to soluble tungsten enhances breast cancer metastasis to the lungs through changes in the surrounding microenvironment. However, more research is required to investigate if changes in the lung microenvironment, following tungsten particulate exposure, can drive tumorigenesis or metastasis to the lung niche. This study examined if inhalation to environmentally relevant concentrations of tungsten particulates caused acute damage to the microenvironment in the lungs and/or systemically using a whole-body inhalation system. Twenty-four female BALB/c mice were exposed to Filtered Air, 0.60 mg/m3, or 1.7 mg/m3 tungsten particulates (<1 µm) for 4 h. Tissue samples were collected at days 1 and 7 post-exposure. Tungsten accumulation in the lungs persisted up to 7 days post-exposure and produced acute changes to the lung microenvironment including increased macrophage and neutrophil infiltration, increased levels of proinflammatory cytokines interleukin 1 beta and C-X-C motif chemokine ligand 1, and an increased percentage of activated fibroblasts (alpha-smooth muscle actin+). Exposure to tungsten also resulted in systemic effects on the bone, including tungsten deposition and transient increases in gene expression of proinflammatory cytokines. Taken together, acute whole-body inhalation of tungsten particulates, at levels commonly observed in occupational and military settings, resulted in changes to the lung and bone microenvironments that may promote tumorigenesis or metastasis and be important molecular drivers of other tungsten-associated lung pathologies such as interstitial lung disease.
吸入钨颗粒是职业和军事环境中暴露的一个相关途径。接触钨合金与肺部病理学发病率的增加有关，包括间质性肺病和癌症。我们已经证明，口服可溶性钨通过改变周围微环境，增强乳腺癌向肺部转移。然而，需要更多的研究来调查在肺部微环境发生变化后，是否会促进肿瘤发生或转移到肺部。本研究通过全身吸入系统，检查吸入环境相关浓度的钨颗粒是否会导致肺部微环境的急性损伤和/或全身性损伤。24 只雌性 BALB/c 小鼠暴露于过滤空气、0.60mg/m3 或 1.7mg/m3 钨颗粒（<1μm）4 小时。在暴露后第 1 天和第 7 天收集组织样本。暴露后 7 天内，肺部的钨积累持续存在，并导致肺部微环境的急性变化，包括巨噬细胞和中性粒细胞浸润增加、促炎细胞因子白细胞介素 1β和 C-X-C 基序趋化因子配体 1 的水平增加，以及激活的成纤维细胞（α-平滑肌肌动蛋白+）的百分比增加。暴露于钨还导致骨骼的全身效应，包括钨沉积和促炎细胞因子基因表达的短暂增加。总之，在职业和军事环境中常见的水平下进行全身急性吸入钨颗粒，会导致肺部和骨骼微环境发生变化，从而促进肿瘤发生或转移，这可能是其他与钨相关的肺部疾病（如间质性肺病）的重要分子驱动因素。
