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羟基化石墨烯量子点诱导人食管上皮细胞 DNA 损伤并破坏微管结构。

Hydroxylated-Graphene Quantum Dots Induce DNA Damage and Disrupt Microtubule Structure in Human Esophageal Epithelial Cells.

机构信息

State Key Laboratory of Radiation Medicine and Protection, Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, People's Republic of China.

Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, People's Republic of China.

出版信息

Toxicol Sci. 2018 Jul 1;164(1):339-352. doi: 10.1093/toxsci/kfy090.

Abstract

Graphene quantum dots (GQDs) have attracted significant interests due to their unique chemical and physical properties. In this study, we investigated the potential effects of hydroxyl-modified GQDs (OH-GQDs) on the human esophageal epithelial cell line HET-1A. Our data revealed significant cytotoxicity of OH-GQDs which decreased the viability of HET-1A in a dose and time-dependent manner. The moderate concentration (25 or 50 µg/ml) of OH-GQDs significantly blocked HET-1A cells in G0/G1 cell cycle phase. An increased percentage of γH2AX-positive and genomically unstable cells were also detected in cells treated with different doses of OH-GQDs (25, 50, and 100 µg/ml). Microarray data revealed that OH-GQDs treatment down-regulated genes related to DNA damage repair, cell cycle regulation and cytoskeleton signal pathways indicating a novel role of OH-GQDs. Consistent with the microarray data, OH-GQDs disrupted microtubule structure and inhibited microtubule regrowth around centrosomes in HET-1A cells. In conclusion, our findings provide important evidence for considering the application of OH-GQDs in biomedical fields.

摘要

石墨烯量子点(GQDs)由于其独特的化学和物理性质而引起了广泛关注。在本研究中,我们研究了羟基修饰的 GQDs(OH-GQDs)对人食管上皮细胞系 HET-1A 的潜在影响。我们的数据显示,OH-GQDs 具有明显的细胞毒性,可剂量和时间依赖性地降低 HET-1A 的活力。中等浓度(25 或 50μg/ml)的 OH-GQDs 可显著将 HET-1A 细胞阻滞在 G0/G1 细胞周期阶段。还检测到用不同剂量的 OH-GQDs(25、50 和 100μg/ml)处理的细胞中γH2AX 阳性和基因组不稳定细胞的比例增加。微阵列数据分析显示,OH-GQDs 处理下调了与 DNA 损伤修复、细胞周期调控和细胞骨架信号通路相关的基因,这表明了 OH-GQDs 的新作用。与微阵列数据一致,OH-GQDs 破坏了 HET-1A 细胞中的微管结构,并抑制了中心体周围微管的再生。总之,我们的研究结果为考虑将 OH-GQDs 应用于生物医学领域提供了重要依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9117/6016703/b353979e367c/kfy090f1.jpg

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