Park Eun-Jung, Lee Gwang-Hee, Han Beom Seok, Lee Byoung-Seok, Lee Somin, Cho Myung-Haing, Kim Jae-Ho, Kim Dong-Wan
Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea,
Arch Toxicol. 2015 Sep;89(9):1557-68. doi: 10.1007/s00204-014-1303-x. Epub 2014 Jul 1.
With the development of nanotechnology, myriad types of novel materials have been discovered at the nanoscale, among which the most interesting material is graphene. However, the toxicity data available on graphene are extremely limited. In this study, we explored toxic response of commercially available graphene nanoplatelets (GNPs) in vivo and in vitro. The GNPs used in this study had a high surface area and feature considerably few defects. In mice, GNPs (2.5 and 5 mg/kg) remained in the lung until 28 days after a single instillation, and the secretion of inflammatory cytokines reached the maximal level at Day 14 and then decreased over time. In vitro study using BEAS-2B cells, a human bronchial epithelial cell line, GNPs located within autophagosome-like vacuoles 24 h after exposure. The GNPs (2.5, 5, 10, and 20 μg/mL) also dose-dependently reduced cell viability, which was accompanied by an increase in the portion of cells in the subG1 and S phases. Moreover, the GNPs down-regulated the generation of reactive oxygen species, suppressed ATP production, caused mitochondria damage, and elevated the levels of autophagy-related proteins. Based on these results, we suggest that GNPs provoked a subchronic inflammatory response in mice and that GNPs induced autophagy accompanying apoptosis via mitochondria damage in vitro.
随着纳米技术的发展,在纳米尺度上发现了无数种新型材料,其中最有趣的材料是石墨烯。然而,关于石墨烯的毒性数据极其有限。在本研究中,我们探索了市售石墨烯纳米片(GNPs)在体内和体外的毒性反应。本研究中使用的GNPs具有高表面积且缺陷极少。在小鼠中,单次滴注后,GNPs(2.5和5mg/kg)在肺中留存至28天,炎性细胞因子的分泌在第14天达到最高水平,然后随时间下降。使用人支气管上皮细胞系BEAS-2B细胞进行的体外研究表明,暴露24小时后GNPs位于自噬体样液泡内。GNPs(2.5、5、10和20μg/mL)还剂量依赖性地降低细胞活力,同时伴随着亚G1期和S期细胞比例的增加。此外,GNPs下调活性氧的产生,抑制ATP生成,导致线粒体损伤,并提高自噬相关蛋白的水平。基于这些结果,我们认为GNPs在小鼠中引发了亚慢性炎症反应,并且在体外GNPs通过线粒体损伤诱导自噬并伴随细胞凋亡。