p53-competent cells and p53-deficient cells display different susceptibility to oxygen functionalized graphene cytotoxicity and genotoxicity

J Appl Toxicol. 2017 Nov;37(11):1333-1345. doi: 10.1002/jat.3472. Epub 2017 Apr 20.

Abstract

Due to the distinctive physical, electrical, and chemical properties of graphene nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial applications are underway. Oxidation of pristine graphene surfaces mitigates its otherwise hydrophobic characteristic thereby improving its biocompatibility and functionality. Yet, the potential widespread use of oxidized graphene derivatives raises concern about adverse impacts on human health. The p53 tumor suppressor protein maintains cellular and genetic stability after toxic exposures. Here, we show that p53 functional status correlates with oxygen functionalized graphene (f-G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells, but not p53-deficient cells, initiated G0 /G1 phase cell cycle arrest, suppressed reactive oxygen species, and entered apoptosis. There was p53-dependent f-G genotoxicity evident as increased structural chromosome damage, but not increased gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic potential for f-G in exposed cells was dependent on the p53 functional status. These findings have broad implications for the safe and effective implementation of oxidized graphene derivatives into biomedical and industrial applications. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Keywords: TK6 and NH32 cell lines; apoptosis; cell cycle; chromosome damage; cytotoxicity; graphene; p53 tumor suppressor; reactive oxygen species.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis / drug effects
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Transformed
  • Chromosome Aberrations / chemically induced
  • Dose-Response Relationship, Drug
  • Graphite / chemistry
  • Graphite / toxicity*
  • Humans
  • Loss of Heterozygosity
  • Nanoparticles / toxicity*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Risk Assessment
  • Time Factors
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Graphite