Oxygen content-related DNA damage of graphene oxide on human retinal pigment epithelium cells

Abstract

Arguments regarding the biocompatibility of graphene-based materials (GBMs) have never ceased. Particularly, the genotoxicity (e.g., DNA damage) of GBMs has been considered the greatest risk to healthy cells. Detailed genotoxicity studies of GBMs are necessary and essential. Herein, we present our recent studies on the genotoxicity of most widely used GBMs such as graphene oxide (GO) and the chemically reduced graphene oxide (RGO) toward human retinal pigment epithelium (RPE) cells. The genotoxicity of GO and RGOs against ARPE-19 (a typical RPE cell line) cells was investigated using the alkaline comet assay, the expression level of phosphorylated p53 determined via Western blots, and the release level of reactive oxygen species (ROS). Our results suggested that both GO and RGOs induced ROS-dependent DNA damage. However, the DNA damage was enhanced following the reduction of the saturated C–O bonds in GO, suggesting that surface oxygen-containing groups played essential roles in the reduced genotoxicity of graphene and had the potential possibility to reduce the toxicity of GBMs via chemical modification.

Genotoxicity of Graphene-Based Materials

“…The main PC parameters measured in the reviewed articles were thickness, lateral size, zeta potential, and hydrodynamic diameter. However, although not so commonly, other parameters such as surface area [ 54 , 55 , 56 ], chemical composition [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], impurity concentration [ 56 , 57 , 63 , 64 , 67 , 68 ], aggregation/agglomeration [ 54 , 60 , 63 , 64 , 69 , 70 ], morphology and/or surface characteristics [ 55 , 57 , 71 , 72 ], thermal stability [ 67 ], elasticity [ 56 ], precipitation in suspension [ 65 ], number of layers [ 54 , 57 , 60 , 61 , 63 , 64 , 71 , 73 , 74 , 75 , 76 , 77 ] hydrophobicity [ …”

“…In two of the articles, a size-dependent effect was observed, showing particles with smaller lateral size having the strongest genotoxic effect [ 73 , 77 ]. Ou and colleagues [ 68 ] observed that GO induced lower levels of DNA damage than rGO, although at high cytotoxic doses. The authors suggested that oxygen-containing functional groups play an essential role, with saturated C-O bonds reducing genotoxicity in comparison with unsaturated C=O bonds.…”

Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review

“…Indirect genotoxicity of GFNs mediated by oxidative stress has been explored in vivo and in vitro. For instance, ROS generation and ROS-dependent DNA damage and genotoxicity were observed in human retinal pigment epithelium (ARPE-19) cells after 24 h exposure to GO and rGO [81]. Similarly, GO and rGO can also trigger genotoxicity of female C57BL/6J mice by induction of oxidative stress [82].…”

“…The oxygen-containing functional groups play a key role in the genotoxicity of GFNs [58,[81][82][83]119]. For example, the rGO with lower oxygen content can induce stronger genotoxicity on ARPE-19 cells than these GO with higher oxygen content, suggesting that GO has a better biocompatibility owing to more saturated C-O bonds [81]. The remove of epoxy groups from the GO surface mitigates GO in vivo genotoxicity toward Xenopus laevis tadpoles [58].…”

Adsorption Properties and Mechanism of Attapulgite to Graphene Oxide in Aqueous Solution

“…For mammals, GO enters various tissues and organs such as the blood, the gastrointestinal tract, heart, kidney, lung, etc., causing damage to these tissues and organs, resulting in various inflammations, acute allergies and even death [ 14 ]. Due to the unique size and morphology of GO, it easily passes through the cell membrane, leading to the destruction of biomolecules such as nucleic acids, lipids and proteins, which in turn leads to DNA damage and induces genotoxicity [ 15 ]. Therefore, in view of the popularity of GO and the possibility of leakage, the research on GO adsorption is urgently needed.…”