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|Author(s):||Amber Nagy; Jennifer A. Hollingsworth; Bin Hu; Andrea Steinbruck; Peter C. Stark; Cristina Rios Valdez; Momchilo Vuyisich; Michael H. Stewart; Donald H. Atha; Bryant C. Nelson; Rashi Iyer;|
|Title:||Functionalization-Dependent Induction of Cellular Survival Pathways by CdSe Quantum Dots in Primary Normal Human Bronchial Epithelial Cells|
|Published:||September 05, 2013|
|Abstract:||Quantum dots (QDs) are semiconductor nanocrystals exhibiting unique optical properties which can be exploited for many practical applications ranging from photovoltaics to biomedical imaging and drug delivery. They are increasingly manufactured in large quantities which can lead to incidences of both occupational and consumer exposure. One primary mechanism of exposure is through inhalation of aerosolized particles; consequently, we chose to investigate the cytotoxic and genotoxic effects of CdSe QDs in primary normal human bronchial epithelial cells (NHBEs). Keeping QD core composition and size constant, 3 nm CdSe QDs were functionalized with mercaptopropionic acid (MPA) or cysteamine (CYST) to render QDs with negative or positive charges, respectively. In the current study, CYST-QDs were found to have significantly increased cytotoxic effects on NHBE cells and also induced significant DNA strand breakage compared to media controls. Significant increases in DNA strand breaks were evident in NHBE cells even in the absence of cytotoxicity and reactive oxygen species formation. DNA damage was confirmed by identifying the presence of p53 binding protein 1 (53BP1) in the nuclei of exposed cells, and subsequent diminishment of p53 from cytoplasmic cellular extracts suggesting that DNA damage may be p53 dependent . Further, high throughout real-time PCR analyses revealed upregulation of GADD45A and proinflammatory cytokine gene expression. Expression of genes involved with DNA repair (BRCA1 and BRCA2) were downregulated in response to QD exposure. These data indicate that cytotoxic assays must be supplemented with genotoxic analyses to better understand cellular responses and the full impact of nanoparticles exposure when making recommendations with regard to risk assessment.|
|Pages:||pp. 8397 - 8411|
|Keywords:||Genotoxicity, Nanomaterials, Quantum Dots, Cytotoxicity, Comet Assay|
|Research Areas:||Bioscience & Health, Nanotech/Environment, Health & Safety|
|PDF version:||Click here to retrieve PDF version of paper (3MB)|