Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy

Abstract

After exposing rat embryonic cells to 20 μg/mL of silver nanoparticle (NP) suspension and their released ions for different time periods, silver nanoparticles were found in cellular nuclei, mitochondria, cytoplasm and lysosomes by transmission electron microscopy (TEM). We also observed mitochondrial destruction, distension of endoplasmic reticulum and apoptotic bodies. Global gene expression analysis showed a total of 279 genes that were up-regulated and 389 genes that were down-regulated in the silver-NP suspension exposure group, while 3 genes were up-regulated and 41 genes were down-regulated in the silver ion exposure group. Further, the GO pathway analysis suggested that these differentially expressed genes are involved in several biological processes, such as energy metabolism, oxygen transport, enzyme activities, molecular binding, etc. It is possible that inhibition of oxygen transport is mediated by the significant down-regulation of genes of the globin family, which might play an important role in silver ion-induced toxicity. KEGG pathway analysis showed that there were 23 signal pathways that were affected in the cells after exposure to silver-NP suspension, but not silver ion alone. The most significant change concerned inflammatory signal pathways, which were only found in silver-NP suspension exposed cells, indicating that inflammatory response might play an important role in the mechanism(s) of silver-NP-induced toxicity. The significant up-regulation of matrix metalloproteinases 3 and 9 suggests that silver NPs could induce extracellular matrix degradation via an inflammatory signaling pathway. The significant up-regulation of secretory leukocyte peptidase inhibitor and serine protease inhibitor 2c was considered to be an embryonic cellular defense mechanism in response to silver-NP-induced inflammation.

• Embryonic cells
• global gene expression
• inflammatory effects
• silver nanoparticles
• ultrastructural damages

Acknowledgements

We would like to thank Dr. Mo Dan (Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control) for her comments and dicussion; and thanks Dr. Chunying Chen and Dr. Ru Bai (National Center for Nanoscience and Nanotechnology, China) for their technical supports for XRD characterization of silver nanoparticles.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was financially supported by the Beijing Natural Science Foundation of China (No. 3112024); National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2012BAK26B00); Principal Scientists Training Fund, National Institutes for Food and Drug Control (2012X2).

Supplementary material available online

Supplemental Figure S1 and Supplemental Tables S1–S8