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纳米和微米尺寸的三价铬颗粒对人角质形成细胞和肺泡上皮细胞中与基因组稳定性相关的细胞毒性和基因表达谱的影响。

Impact of Nano- and Micro-Sized Chromium(III) Particles on Cytotoxicity and Gene Expression Profiles Related to Genomic Stability in Human Keratinocytes and Alveolar Epithelial Cells.

作者信息

Schumacher Paul, Fischer Franziska, Sann Joachim, Walter Dirk, Hartwig Andrea

机构信息

Department of Food Chemistry and Toxicology, Institute of Applied Biosciences (IAB), Karlsruhe Institute of Technology (KIT), Adenauerring 20a, 76131 Karlsruhe, Germany.

Institute of Physical Chemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.

出版信息

Nanomaterials (Basel). 2022 Apr 11;12(8):1294. doi: 10.3390/nano12081294.

Abstract

Exposure to Cr(VI) compounds has been consistently associated with genotoxicity and carcinogenicity, whereas Cr(III) is far less toxic, due to its poor cellular uptake. However, contradictory results have been published in relation to particulate CrO. The aim of the present study was to investigate whether Cr(III) particles exerted properties comparable to water soluble Cr(III) or to Cr(VI), including two nano-sized and one micro-sized particles. The morphology and size distribution were determined by TEM, while the oxidation state was analyzed by XPS. Chromium release was quantified via AAS, and colorimetrically differentiated between Cr(VI) and Cr(III). Furthermore, the toxicological fingerprints of the CrO particles were established using high-throughput RT-qPCR and then compared to water-soluble Cr(VI) and Cr(III) in A549 and HaCaT cells. Regarding the CrO particles, two out of three exerted only minor or no toxicity, and the gene expression profiles were comparable to Cr(III). However, one particle under investigation released considerable amounts of Cr(VI), and also resembled the toxicity profiles of Cr(VI); this was also evident in the altered gene expression related to DNA damage signaling, oxidative stress response, inflammation, and cell death pathways. Even though the highest toxicity was found in the case of the smallest particle, size did not appear to be the decisive parameter, but rather the purity of the Cr(III) particles with respect to Cr(VI) content.

摘要

接触六价铬化合物一直与遗传毒性和致癌性相关,而三价铬的毒性要小得多,因为其细胞摄取能力较差。然而,关于颗粒状氧化铬的研究结果却相互矛盾。本研究的目的是调查三价铬颗粒是否具有与水溶性三价铬或六价铬相当的性质,包括两种纳米尺寸和一种微米尺寸的颗粒。通过透射电子显微镜(TEM)测定形态和尺寸分布,同时用X射线光电子能谱(XPS)分析氧化态。通过原子吸收光谱法(AAS)对铬的释放进行定量,并通过比色法区分六价铬和三价铬。此外,利用高通量逆转录定量聚合酶链反应(RT-qPCR)建立氧化铬颗粒的毒理学指纹图谱,然后在A549和HaCaT细胞中与水溶性六价铬和三价铬进行比较。对于氧化铬颗粒,三种颗粒中有两种仅表现出轻微毒性或无毒性,其基因表达谱与三价铬相当。然而,一种被研究的颗粒释放出大量六价铬,其毒性特征也与六价铬相似;这在与DNA损伤信号传导、氧化应激反应、炎症和细胞死亡途径相关的基因表达变化中也很明显。尽管在最小颗粒的情况下发现了最高毒性,但尺寸似乎不是决定性参数,而是三价铬颗粒相对于六价铬含量的纯度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08d/9029936/cf507140524a/nanomaterials-12-01294-g001a.jpg

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