Current understanding of toxicity mechanisms of nanoparticles is still far from comprehensive, partly because of the neglect of control factors such as the dependence of mechanism activation on the exposure dosage and particle size. To reveal molecular mechanisms of silver nanoparticle (AgNP) toxicity, the model ciliate Paramecium multimicronucleatum was exposed for 12 h to different concentrations of AgNPs with particle size of 20 nm (0.08, 0.12, and 0.30 mg/l) and 40 nm (0.08 and 0.30 mg/l). Transcriptomes of the tested ciliates were then analyzed based on dendrograms of gene expression, Gene Ontology (GO) terms, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, and up- and down-regulated genes. Results showed that: (1) toxicity mechanisms of AgNP revealed by analyses of GO and KEEG were significantly involved in the metabolic pathways of nutrients and the biosynthesis of macromolecules; (2) the top five up-regulated genes were mainly related to biological oxidation, biosynthesis, and oxidative stress, while top five down-regulated genes were mainly related to glycolysis; (3) activated mechanisms varied both in quantity and in type with dosages and particle sizes of AgNPs; (4) AgNP-treatments with different exposure dosages and particle sizes can produce the same toxicity in terms of 12 h-EC₅₀, but the underlying molecular mechanisms differed significantly. In brief, this study provides insights into the molecular mechanisms of AgNP toxicity through transcriptome analyses and confirmed their dependence of activation on the exposure dosage and particle size of AgNPs.

目前对纳米颗粒毒性机制的理解还远未全面，部分原因是忽略了机制激活对暴露剂量和粒径的依赖性等控制因素。为了揭示银纳米颗粒 (AgNP) 毒性的分子机制，模型纤毛虫草履虫多微核暴露于不同浓度的 AgNPs 12 小时，粒径分别为 20 nm（0.08、0.12 和 0.30 mg/l）和 40 nm（0.08 和 0.30 mg/l）。然后基于基因表达的树状图、基因本体论 (GO) 术语、KEGG（京都基因和基因组百科全书）途径以及上调和下调基因分析测试的纤毛虫的转录组。结果表明：（1）GO和KEEG分析揭示的AgNP毒性机制显着参与了营养物质的代谢途径和大分子的生物合成；(2)前5位上调基因主要与生物氧化、生物合成和氧化应激有关，而前5位下调基因主要与糖酵解有关；(3) 激活机制在数量和类型上随 AgNPs 的剂量和粒径而变化；₅₀，但潜在的分子机制存在显着差异。简而言之，本研究通过转录组分析提供了对 AgNP 毒性分子机制的见解，并证实了它们的活化对 AgNPs 的暴露剂量和粒径的依赖性。