Xia Qiyue, Li Hongxia, Liu Ying, Zhang Shuyang, Feng Qiyi, Xiao Kai
National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
West China School of Public Health, Sichuan University, Chengdu, 610041, People's Republic of China.
J Biomed Mater Res A. 2017 Mar;105(3):710-719. doi: 10.1002/jbm.a.35944. Epub 2016 Nov 7.
Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24-h exposure. Furthermore, 5 nm AuNPs induced cell cycle arrest in G1 phase in response to DNA damage, and promoted the production of reactive oxygen species (ROS). In the chromosomal aberration test, AuNPs exposure did not increase in the frequency of chromosomal aberrations in Chinese hamster lung (CHL) cells. In the standard in vivo micronucleus test, no obvious increase in the frequency of micronucleus formation was found in mice after 4 day exposure of AuNPs. However, when the exposure period was extended to 14 days, 5 nm AuNPs presented significant clastogenic damage, with a dose-dependent increase of micronuclei frequencies. This finding suggests that particle size plays an important role in determining the genotoxicity of AuNPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 710-719, 2017.
尽管金纳米颗粒(AuNPs)在生物医学领域的应用日益广泛,但其毒理学效应仍需深入了解。在本研究中,我们使用一系列体外和体内遗传毒性试验,评估了市售不同尺寸(5、20和50纳米)的AuNPs的遗传毒性潜力。在彗星试验中,在测试浓度下,20纳米和50纳米的AuNPs未在HepG2细胞中诱导明显的DNA损伤,而5纳米的纳米颗粒在暴露24小时后诱导了剂量依赖性的DNA损伤增加。此外,5纳米的AuNPs响应DNA损伤诱导细胞周期停滞在G1期,并促进活性氧(ROS)的产生。在染色体畸变试验中,AuNPs暴露未增加中国仓鼠肺(CHL)细胞中的染色体畸变频率。在标准的体内微核试验中,AuNPs暴露4天后,小鼠微核形成频率未明显增加。然而,当暴露期延长至14天时,5纳米的AuNPs表现出明显的致断裂损伤,微核频率呈剂量依赖性增加。这一发现表明,颗粒大小在决定AuNPs的遗传毒性方面起着重要作用。©2016威利期刊公司。《生物医学材料研究杂志》A部分:105A:710 - 719,2017年。