Hu Moyan, Palić Dušan
Chair for Fish Diseases and Fisheries Biology, Faculty of Veterinary Medicine, Ludwig Maximilian University of Munich, Munich, Germany.
Toxicol Rep. 2020 Jun 3;7:743-751. doi: 10.1016/j.toxrep.2020.05.007. eCollection 2020.
The release of nanoparticles into the environment can interfere with the health of the exposed organisms. MicroRNAs have been suggested as potential toxicology biomarkers. The expression of potential zebrafish nano-toxicity biomarker miRNAs in our previous study was validated in THP-1 human monocytic cell line after exposure to polystyrene (PSNPs) and ARS labeled Titanium dioxide nanoparticles (nano-TiO-ARS). miRNAs expression post exposure to PLGA nanoparticles and BioParticles was used to exclude potential activation and engagement of miRNAs through phagocytosis or pro-inflammatory specific responses. miR-155-5p showed the highest potential to be used as biomarker for PSNPs and nano-TiO-ARS induced toxicity. To determine effects of PSNPs and nano-TiO-ARS on genotoxicity, time and dose dependent DNA damage profile was established. Severe DNA damage was triggered by both nanoparticles, and expression of DNA damage repairing genes was elevated post nano-TiO-ARS, but not post PSNPs exposure, questioning the utility of the comet assay as universal assessment tool for genotoxicity induced by nanoparticles in general. Transfection of miR-155-5p mimic influenced the expression of miR-155-5p related, DNA damage responsible genes post both nano-TiO-ARS and PSNPs exposure. Transfection results suggest significant involvement of miR-155-5p in gene repair mechanisms triggered by adverse effects of PSNPs and nano-TiO-ARS on monocytes.
纳米颗粒释放到环境中会干扰暴露生物体的健康。微小RNA已被认为是潜在的毒理学生物标志物。在我们之前的研究中，斑马鱼潜在纳米毒性生物标志物微小RNA的表达在暴露于聚苯乙烯（PSNPs）和ARS标记的二氧化钛纳米颗粒（纳米TiO₂-ARS）后的THP-1人单核细胞系中得到了验证。暴露于PLGA纳米颗粒和生物颗粒后的微小RNA表达用于排除通过吞噬作用或促炎特异性反应对微小RNA的潜在激活和参与。miR-155-5p显示出作为PSNPs和纳米TiO₂-ARS诱导毒性生物标志物的最大潜力。为了确定PSNPs和纳米TiO₂-ARS对遗传毒性的影响，建立了时间和剂量依赖性DNA损伤图谱。两种纳米颗粒均引发了严重的DNA损伤，纳米TiO₂-ARS暴露后DNA损伤修复基因的表达升高，但PSNPs暴露后未升高，这对彗星试验作为纳米颗粒诱导遗传毒性的通用评估工具的实用性提出了质疑。miR-155-5p模拟物的转染影响了纳米TiO₂-ARS和PSNPs暴露后与miR-155-5p相关的、负责DNA损伤的基因的表达。转染结果表明，miR-155-5p在PSNPs和纳米TiO₂-ARS对单核细胞的不利影响引发的基因修复机制中起重要作用。
