الفهرس 
Introduction and aim of workOnly 14 pages are availabe for public view
 |  | from | 206 |  |  |
| | | from | 206 | | |
Abstract
The rapidly growing interest in using graphene-based nanoparticles in a wide range of applications increases human exposure and risk; this is due to the unique physicochemical properties of graphene nanoparticles. However, very few studies have investigated the genotoxicity and mutagenicity of the widely used graphene oxide (GO) nanoparticles in vivo. Consequently, the current study was designed to investigate the possible induction of chromosomal and DNA damage by GO nanoparticles and their impact on the tissue architecture in mice. This study estimated also the possible genotoxicity and mutagenicity of GO nanoparticles as well as possible oxidative stress induction in the mice liver and brain tissues. Oral administration of GO nanoparticles for one or five consecutive days at the three dose levels 10, 20 and 40mg/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. GO nanoparticles also induced mutations in the p53gene (exons 6&7) and presenilin gene (exon 5) as well as increasing the expression of p53 protein. Positive p53 reaction in 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. In conclusion, our data explain that oral administration of GO nanoparticles induced chromosomal and DNA damage in a dose-dependent manner as well as histological injuries, oral administration of GO nanoparticles also induced genomic instability and mutagenicity by induction of oxidative stress in the mice liver and brain tissues in both acute and subacute treatments.