Gomaa I O, Kader M Ha, Salah T A, Heikal O A
Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt.
Drug Discov Ther. 2013 Jun;7(3):116-23.
For successful application of nanomaterials in bioscience, it is essential to understand the biological fate and potential toxicity of nanoparticles. The aim of this study is to evaluate the genetic safety of magnetite nanoparticles (MNPs) (Fe(3)O(4)) in order to provide their diverse applications in life sciences, such as drug development, protein detection, and gene delivery. Concentrations of 10 ppm, 30 ppm, and 70 ppm (10-70 μg/mL) of the MNPs of 8.0 ± 2.0 nm were used. Characterization of MNPs was done with transmission electron microscopy (TEM), X-Ray Diffractometry (XRD) and a vibrating sample magnetometer (VSM). The MNPs mutagenic potential was evaluated using the Salmonella Ames test with Salmonella strains TA100, TA2638, TA102, and TA98 in the presence and the absence of metabolic activation with S9-liver extract. Genetic mutations at the chromosomal level and extent of DNA damage using the alkaline Comet assay were applied to peripheral blood lymphocytes and HEK-293 cell lines respectively. There were significant changes in the results of the Salmonella mutagenicity test at the 70 ppm concentration of MNPs which might reflect their mutagenic activity at higher concentrations. Cytogenetic evaluation revealed the absence of genetic mutations at the chromosomal level. The extent of DNA damage quantified by Comet assay and the mutagenicity study using Ames test were significantly correlated for the MNPs. Our results indicated that magnetite nanoparticles with the defined physicochemical properties caused apparent toxicity at higher concentrations of 30 ppm and 70 ppm without chromosomal abnormalities under the experimental conditions of this study.
为了使纳米材料在生物科学中成功应用，了解纳米颗粒的生物学命运和潜在毒性至关重要。本研究的目的是评估磁铁矿纳米颗粒（MNPs）（Fe(3)O(4)）的遗传安全性，以便为其在生命科学中的多种应用提供依据，如药物开发、蛋白质检测和基因传递。使用了浓度为10 ppm、30 ppm和70 ppm（10 - 70μg/mL）、尺寸为8.0±2.0 nm的MNPs。通过透射电子显微镜（TEM）、X射线衍射仪（XRD）和振动样品磁强计（VSM）对MNPs进行了表征。在有和没有S9 - 肝提取物代谢激活的情况下，使用鼠伤寒沙门氏菌TA100、TA2638、TA102和TA98菌株的沙门氏菌Ames试验评估了MNPs的诱变潜力。分别对外周血淋巴细胞和HEK - 293细胞系应用碱性彗星试验检测染色体水平的基因突变和DNA损伤程度。在MNPs浓度为70 ppm时，沙门氏菌诱变性试验结果有显著变化，这可能反映了其在较高浓度下的诱变活性。细胞遗传学评估显示在染色体水平上没有基因突变。通过彗星试验量化的DNA损伤程度与使用Ames试验的诱变性研究结果在MNPs方面显著相关。我们的结果表明，在本研究的实验条件下，具有确定理化性质的磁铁矿纳米颗粒在30 ppm和70 ppm的较高浓度下会引起明显毒性，但无染色体异常。
