Nanodiamond-mediated impairment of nucleolar activity is accompanied by oxidative stress and DNMT2 upregulation in human cervical carcinoma cells

Abstract

Because applications of nanomaterials in nanomedicine and nanotechnology are rapidly increasing, nanodiamond (ND) health risk assessment is urgently needed. In the present study, we used HeLa cell model to evaluate nanodiamond biocompatibility. We found ND-mediated cytotoxicity, proliferation inhibition and oxidative stress. Conversely, ND-associated genotoxicity was limited to higher concentrations used. Nanodiamond was also recognized as a hypermethylating agent. ND-associated redox imbalance contributed to nucleolar stress: size and number of nucleoli were affected, and release of nucleolar protein RRN3 occurred. Surprisingly, we did not observe stress-induced RNA depletion. In contrast, RNA was stabilized: total RNA level and integrity (28S/18S rRNA ratio) were unaffected. After nanodiamond treatment, upregulation of DNA methyltransferase 2 (DNMT2) was shown. Perhaps, DNMT2, as a part of the regulatory loop of metabolic pathways through RNA methylation, may contribute to RNA stabilization and confer stress resistance after nanodiamond treatment. In conclusion, using HeLa cell model, we showed that ND biocompatibility is limited and special care should be taken when introducing ND-based biomaterials to biological systems.

Keywords: Cytotoxicity; DNMT2; Nanodiamond; Nucleolar stress; ROS.