Evaluation of Graphene Oxide Induced Cellular Toxicity and Transcriptome Analysis in Human Embryonic Kidney Cells

作者：Sangiliyandi Gurunathan, Muhammad Arsalan Iqbal, Muhammad Qasim, Chanhyeok Park, Hyunjin Yoo, Jeong Ho Hwang, Sang Jun Uhm, Hyuk Song, Chankyu Park, Jeong Tae, Youngsok Choi, Jin‐Hoi Kim, Kwonho Hong · 发表于：Nanomaterials · 年份：2019 · DOI：10.3390/nano9070969 · 被引用次数：127 · 研究领域：Graphene and Nanomaterials Applications、Nanoparticles: synthesis and applications、Carbon and Quantum Dots Applications

Graphene, a two-dimensional carbon sheet with single-atom thickness, shows immense promise in several nanoscientific and nanotechnological applications, including in sensors, catalysis, and biomedicine. Although several studies have shown the cytotoxicity of graphene oxide in different cell types, there are no comprehensive studies on human embryonic kidney (HEK293) cells that include transcriptomic analysis and an in vitro investigation into the mechanisms of cytotoxicity following exposure to graphene oxide. Therefore, we exposed HEK293 cells to different concentrations of graphene oxide for 24 h and performed several cellular assays. Cell viability and proliferation assays revealed a significant dose-dependent cytotoxic effect on HEK293 cells. Cytotoxicity assays showed increased lactate dehydrogenase (LDH) leakage and reactive oxygen species (ROS) generation, and decreased levels of reduced glutathione (GSH) and increased level of oxidized glutathione indicative of oxidative stress. This detailed mechanistic approach showed that graphene oxide exposure elicits significant decreases in mitochondrial membrane potential and ATP synthesis, as well as in DNA damage and caspase 3 activity. Furthermore, our RNA-Seq analysis revealed that HEK293 cells exposed to graphene oxide significantly altered the expression of genes involved in multiple apoptosis-related biological pathways. Moreover, graphene oxide exposure perturbed the expression of key transcription factors, promoting t...