Graphene Oxide Negatively Regulates Cell Cycle in Embryonic Fibroblast Cells

Abstract

Ehsan Hashemi,1– 3 Omid Akhavan,4 Mehdi Shamsara,1,2 Saeid Ansari Majd,2 Mohammad Hossein Sanati,5 Morteza Daliri Joupari,1,2 Abbas Farmany6 1Animal Biotechnology Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; 2National Research Center for Transgenic Mouse, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; 3Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Physics, Sharif University of Technology, Tehran, Iran; 5Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; 6Dental Research Center, Hamadan University of Medical Sciences, Hamadan, IranCorrespondence: Morteza Daliri Joupari; Abbas Farmany Tel [phone]Fax [phone]Email [email protected]; [email protected]: Unique properties of graphene and its derivatives make them attractive in the field of nanomedicine. However, the mass application of graphene might lead to side effects, which has not been properly addressed in previous studies, especially with regard to its effect on the cell cycle.Methods: The effect of two concentrations (100 and 200 μg/mL) of nano- and microsized graphene oxide (nGO and mGO) on apoptosis, cell cycle, and ROS generation was studied. The effect of both sizes on viability and genotoxicity of the embryonic fibroblast cell cycle was evaluated. MTT and flow cytometry were applied to evaluate the effects of graphene oxide (GO) nanosheets on viability of cells. Apoptosis and cell cycle were analyzed by flow cytometry.Results: The results of this study showed that GO disturbed the cell cycle and nGO impaired cell viability by inducing cell apoptosis. Interestingly, both nGO and mGO blocked the cell cycle in the S phase, which is a critical phase of the cell cycle. Upregulation of TP53-gene transcripts was also detected in both nGO- and mGO-treated cells compared to the control, especially at 200 μg/mL. DNA content of the treated cells increased; however, because of DNA degradation, its quality was decreased.Conclusion: In conclusion, graphene oxide at both nano- and micro-scale damages cell physiology and increases cell population in the S phase of the cell cycle.Keywords: apoptosis, cell cycle, fibroblast cell, graphene, TP53 gene

Keywords

• apoptosis
• cell cycle
• fibroblast cell
• graphene
• tp53 gene