title: Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells.
abstract: Despite graphene being proposed for a multitude of biomedical applications, there is a dearth in the fundamental cellular and molecular level understanding of how few-layer graphene (FLG) interacts with human primary cells. Herein, using human primary umbilical vein endothelial cells as model of vascular transport, we investigated the basic mechanism underlying the biological behavior of graphene. Mechanistic toxicity studies using a battery of cell based assays revealed an organized oxidative stress paradigm involving cytosolic reactive oxygen stress, mitochondrial superoxide generation, lipid peroxidation, glutathione oxidation, mitochondrial membrane depolarization, enhanced calcium efflux, all leading to cell death by apoptosis/necrosis. We further investigated the effect of graphene interactions using cDNA microarray analysis and identified potential adverse effects by down regulating key genes involved in DNA damage response and repair mechanisms. Single cell gel electrophoresis assay/Comet assay confirmed the DNA damaging potential of graphene towards human primary cells.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin, Kerala, India.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Sasidharan
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin, Kerala, India.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Swaroop
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin, Kerala, India.
authors.forename: Parwathy
authors.initials: P
authors.lastname: Chandran
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin, Kerala, India.
authors.forename: Shantikumar
authors.initials: S
authors.lastname: Nair
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Cochin, Kerala, India. Electronic address: manzoork@aims.amrita.edu.
authors.forename: Manzoor
authors.initials: M
authors.lastname: Koyakutty
mesh_terms: D017209:Apoptosis; D004247:DNA; D004249:DNA Damage; D000091344:Filaggrin Proteins; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D017382:Reactive Oxygen Species; D006108:Graphite; D004247:DNA
keywords: DNA damage; Few-layer graphene; Human primary cells; Microarray; Oxidative stress