Induction of chromosomal and DNA damage and histological alterations by graphene oxide nanoparticles in Swiss mice.

The unique physicochemical properties of graphene oxide (GO) nanoparticles increase their uses in a wide range of applications that increase their release into the environment, and thus human exposure. However, the in vivo clastogenicity and genotoxicity of GO nanoparticles have not been well investigated. The current study was, therefore, designed to investigate the possible induction of chromosomal and DNA damage by GO nanoparticles and their impact on the tissue architecture in mice. Oral administration of GO nanoparticles for one or five consecutive days at the three dose levels 10, 20 or 40 mg/kg significantly increased the micronuclei and DNA damage levels in a dose-dependent manner in mice bone marrow cells, as well as caused, histological lesions including apoptosis, necrosis, inflammations and cells degeneration in the mice liver and brain tissue sections compared to the normal control mice. Thus, we concluded that oral administration of GO nanoparticles induced chromosomal and DNA damage in a dose-dependent manner as well as histological injuries in both acute and subacute treatments.

Estimation of genomic instability and mutation induction by graphene oxide nanoparticles in mice liver and brain tissues.

The rapidly growing interest in using graphene-based nanoparticles in a wide range of applications increases human exposure and risk. However, very few studies have investigated the genotoxicity and mutagenicity of the widely used graphene oxide (GO) nanoparticles in vivo. Consequently, this study estimated the possible genotoxicity and mutagenicity of GO nanoparticles as well as possible oxidative stress induction in the mice liver and brain tissues. Nano-GO particles administration at the dose levels of 10, 20, or 40 mg/kg for one or five consecutive days significantly increased the DNA breakages in a dose-dependent manner that disrupts the genetic material and causes genomic instability. GO nanoparticles also induced mutations in the p53 (exons 6&7) and presenilin (exon 5) genes as well as increasing the expression of p53 protein. Positive p53 reaction in the liver (hepatic parenchyma) and brain (cerebrum, cerebellum, and hippocampus) sections showed significant increase of p53 immunostaining. Additionally, induction of oxidative stress was proven by the significant dose-dependent increases in the malondialdehyde level and reductions in both the level of reduced glutathione and activity of glutathione peroxidase observed in GO nanoparticles administered groups. Acute and subacute oral administration of GO nanoparticles induced genomic instability and mutagenicity by induction of oxidative stress in the mice liver and brain tissues.