title: Differential genotoxic and epigenotoxic effects of graphene family nanomaterials (GFNs) in human bronchial epithelial cells.
abstract: The widespread applications of graphene family nanomaterials (GFNs) raised the considerable concern over human health and environment. The cyto-genotoxic potentiality of GFNs has attracted much more attention, albeit the potential effects on the cellular epigenome remain largely unknown. The effects of GFNs on cellular genome were evaluated with single and double stranded DNA damage and DNA repair gene expressions while the effects on epigenome was accomplished by addressing the global DNA methylation and expression of DNA methylation machineries at non-cytotoxic to moderately cytotoxic doses in in vitro system. We used five different representatives of GFNs-pristine (GNP-Prist), carboxylated (GNP-COOH) and aminated (GNP-NH2) graphene nanoplatelets as well as single layer (SLGO) and few layer (FLGO) graphene oxide. The order of single stranded DNA damage was observed as GNP-Prist ≥ GNP-COOH>GNP-NH2≥FLGO>SLGO at 10mg/L and marked dose dependency was found in SLGO. The GFNs possibly caused genotoxicity by affecting nucleotide excision repair and non-homologus end joining repair systems. Besides, dose dependent increase in global DNA methylation (hypermethylation) were observed in SLGO/FLGO exposure and conversely, GNPs treatment caused hypomethylation following the order as GNP-COOH>GNP-NH2 ≥ GNP-Prist. The decrements of DNA methyltransferase (DNMT3B gene) and methyl-CpG binding domain protein (MBD1) genes were probably the cause of global hypomethylation induced by GNPs. Conversely, the de novo methylation through the up-regulation of DNMT3B and MBD1 genes gave rise to the global DNA hypermethylation in SLGO/FLGO treated cells. In general, the GFNs induced genotoxicity and alterations of global DNA methylation exhibited compounds type specificity with differential physico-chemical properties. Taken together, our study suggests that the GFNs could cause more subtle changes in gene expression programming by modulating DNA methylation status and this information would be helpful for their prospective use in biomedical field.
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.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: JiSu
authors.initials: J
authors.lastname: Yang
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. Electronic address: jinhchoi@uos.ac.kr.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
mesh_terms: D001980:Bronchi / Q000187:drug effects*; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D005809:Genes, Regulator / Q000187:drug effects; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D049329:Nanostructures / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000187:drug effects*; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D006108:Graphite; D009153:Mutagens; D000097584:DNA Methyltransferase 3B
keywords: DNA damage-repair; DNA demethylases (TETs); DNA methyltransferases (DNMTs); Global DNA methylation; Graphene family nanomaterials (GFNs)