title: 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.
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mytych
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Department of Biochemistry and Cell Biology, University of Rzeszow, Zelwerowicza 4, 35-601 Rzeszow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewinska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielak-Zmijewska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Grabowska
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Department of Plant Physiology, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zebrowski
authors.affiliation: Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland. Electronic address: mawnuk@gmail.com.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wnuk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002466:Cell Nucleolus / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D058612:Nanodiamonds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D058612:Nanodiamonds; D000255:Adenosine Triphosphate; D004248:DNA (Cytosine-5-)-Methyltransferases; C112218:TRDMT1 protein, human
keywords: Cytotoxicity; DNMT2; Nanodiamond; Nucleolar stress; ROS