title: A systems toxicology approach to the surface functionality control of graphene-cell interactions.
abstract: The raised considerable concerns about the possible environmental health and safety impacts of graphene nanomaterials and their derivatives originated from their potential widespread applications. We performed a comprehensive study about biological interaction of grapheme nanomaterials, specifically in regard to its differential surface functionalization (oxidation status), by using OMICS in graphene oxide (GO) and reduced graphene oxide (rGO) treated HepG2 cells. Differential surface chemistry (particularly, oxidation - O/C ratio) modulates hydrophobicity/philicity of GO/rGO which in turn governs their biological interaction potentiality. Similar toxic responses (cytotoxicity, DNA damage, oxidative stress) with differential dose dependency were observed for both GO and rGO but they exhibited distinct mechanism, such as, hydrophilic GO showed cellular uptake, NADPH oxidase dependent ROS formation, high deregulation of antioxidant/DNA repair/apoptosis related genes, conversely, hydrophobic rGO was found to mostly adsorbed at cell surface without internalization, ROS generation by physical interaction, poor gene regulation etc. Global gene expression and pathway analysis displayed that TGFβ1 mediated signaling played the central role in GO induced biological/toxicological effect whereas rGO might elicited host-pathogen (viral) interaction and innate immune response through TLR4-NFkB pathway. In brief, the distinct biological and molecular mechanisms of GO/rGO were attributed to their differential surface oxidation status.
authors.affiliation: School of Environmental Engineering, Graduate School of Energy and Environmental system Engineering, University of Seoul, 163 Siripdaero, Dongdaemun-gu, Seoul 130-743, Republic of Korea.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Eom
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D020869:Gene Expression Profiling; D023281:Genomics; D006108:Graphite / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013499:Surface Properties; D049490:Systems Biology
chemical_list: D001672:Biocompatible Materials; D010087:Oxides; D017382:Reactive Oxygen Species; D006108:Graphite
keywords: Graphene oxide (GO); Reduced graphene oxide (rGO); Surface oxidation state; Systems toxicology; TGFβ1 pathway; TLR4–NFkB pathway