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对仓鼠肺部暴露于滑石粉后颗粒的分析:对致病性的影响。

Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity.

机构信息

Penn State DuBois, Pennsylvania State University, Dubois, PA, 15801, USA.

John J. Godleski MD PLLC, 304 Central Ave, Milton, MA, 02186, USA.

出版信息

Part Fibre Toxicol. 2020 Jun 4;17(1):20. doi: 10.1186/s12989-020-00356-0.

DOI:10.1186/s12989-020-00356-0
PMID:32498698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7271432/
Abstract

BACKGROUND

Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used.

RESULTS

SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals.

CONCLUSION

Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

摘要

背景

滑石,一种含水的镁硅酸盐,常用于生殖器卫生,在病例对照研究中与卵巢癌有关。已经描述了它引起细胞炎症、损伤和功能变化的潜力。这类研究的一个并发症是,滑石制剂可能会被其他物质污染。(Beck 等人的一项先前研究。Toxicol Appl Pharmacol 87:222-34, 1987)使用仓鼠模型研究了滑石和花岗岩粉尘暴露对各种生化和细胞炎症标志物的影响。我们目前的研究访问了该 1987 年研究中使用的关键材料;我们使用现代扫描电子显微镜和能量色散 X 射线分析 (SEM/EDX) 重新分析了原始滑石粉尘,以检测污染物。我们还使用偏光显微镜检查了原始的支气管肺泡灌洗液 (BAL) 细胞,以量化与细胞相关的双折射颗粒,从而深入了解使用的滑石。

结果

SEM/EDX 分析表明,石棉纤维、石英和有毒金属颗粒在原始滑石粉中的含量低于检测限。然而,长宽比≥3:1 的纤维占注入材料的 22%,主要是纤维状滑石。(基于 Mg/Si 原子重量%比)是最丰富的化学特征,其余的则是各种含有其他元素的镁硅酸盐。BAL 细胞计数证实了存在急性炎症,这是在气管内注入后发生的。对与细胞相关的双折射颗粒吞噬作用的测量表明,滑石、花岗岩和对照暴露之间存在显著差异,与花岗岩相比,滑石的初始摄取量较高,但在 14 天的实验中,灌洗细胞对滑石的吞噬作用明显低于花岗岩。观察到巨噬细胞吞噬滑石纤维,并且在暴露于滑石的动物的灌洗细胞中的巨噬细胞、中性粒细胞和多核巨细胞中发现了双折射颗粒。

结论

我们的数据支持这样的论点,即即使没有石棉和其他已知的有毒污染物,滑石也可能引发炎症并导致肺部疾病。我们的发现支持(Beck 等人的结论。Toxicol Appl Pharmacol 87:222-34, 1987)研究。通过偏光显微镜和 SEM/EDX 分析分析颗粒暴露,鉴定出纤维状滑石,并证明了一种独特的颗粒摄入受损模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/2c17b2060b62/12989_2020_356_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/6269df72b83d/12989_2020_356_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/2375cb5c8883/12989_2020_356_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/8a91071f9053/12989_2020_356_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/ccc9a0f677f8/12989_2020_356_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/994c98d248f8/12989_2020_356_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/2c17b2060b62/12989_2020_356_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/6269df72b83d/12989_2020_356_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/2375cb5c8883/12989_2020_356_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/8a91071f9053/12989_2020_356_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/ccc9a0f677f8/12989_2020_356_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/994c98d248f8/12989_2020_356_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00b/7271432/2c17b2060b62/12989_2020_356_Fig6_HTML.jpg

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