Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells

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• 作者：Abhilash Sasidharan ; PhD¹ ; Siddharth Swaroop ; MTech ; Parwathy Chandran ; PhD¹ ; Shantikumar Nair ; PhD ; Manzoor Koyakutty ; PhD ; ^{manzoork@aims.amrita.edu" class="auth_mail" title="E-mail the corresponding author} ; ^{manzoork@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Few-layer graphene ; Human primary cells ; Oxidative stress ; Microarray ; DNA damage
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：12
• 期：5
• 页码：1347-1355
• 全文大小：2002 K

文摘

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.