Abstract:
Metal oxide nanoparticles (MONP/s) induce DNA damage, which is influenced by their physicochemical properties. In this study, the high-throughput CometChip and micronucleus (MicroFlow) assays were used to investigate DNA and chromosomal damage in mouse lung epithelial cells induced by nano and bulk sizes of zinc oxide, copper oxide, manganese oxide, nickel oxide, aluminum oxide, cerium oxide, titanium dioxide, and iron oxide. Ionic forms of MONPs were also included. The study evaluated the impact of solubility, surface coating, and particle size on response. Correlation analysis showed that solubility in the cell culture medium was positively associated with response in both assays, with the nano form showing the same or higher response than larger particles. A subtle reduction in DNA damage response was observed post-exposure to some surface-coated MONPs. The observed difference in genotoxicity highlighted the mechanistic differences in the MONP-induced response, possibly influenced by both particle stability and chemical composition. The results highlight that combinations of properties influence response to MONPs and that solubility alone, while playing an important role, is not enough to explain the observed toxicity. The results have implications on the potential application of read-across strategies in support of human health risk assessment of MONPs.
摘要:
金属氧化物纳米颗粒(MONP/s)诱导DNA损伤,这受到它们的物理化学性质的影响。在这项研究中,高通量CometChip和微核(MicroFlow)分析用于研究纳米和体积大小的氧化锌诱导的小鼠肺上皮细胞的DNA和染色体损伤,氧化铜,氧化锰,氧化镍,氧化铝,氧化铈,二氧化钛,和氧化铁。还包括离子形式的MONP。该研究评估了溶解度的影响,表面涂层,和响应的颗粒大小。相关分析表明,在细胞培养基中的溶解度与反应呈正相关。与纳米形式显示相同或更高的响应比较大的颗粒。在暴露于一些表面涂覆的MONP后观察到DNA损伤响应的细微降低。观察到的遗传毒性差异突出了MONP诱导反应的机制差异,可能受到颗粒稳定性和化学成分的影响。结果突出表明,性质的组合会影响对MONP的反应,并且单独的溶解度,在发挥重要作用的同时,不足以解释观察到的毒性。结果对阅读策略在支持MONP人类健康风险评估中的潜在应用具有影响。