title: Functionalization-dependent induction of cellular survival pathways by CdSe quantum dots in primary normal human bronchial epithelial cells.
abstract: Quantum dots (QDs) are semiconductor nanocrystals exhibiting unique optical properties that can be exploited for many practical applications ranging from photovoltaics to biomedical imaging and drug delivery. A significant number of studies have alluded to the cytotoxic potential of these materials, implicating Cd-leaching as the causal factor. Here, we investigated the role of heavy metals in biological responses and the potential of CdSe-induced genotoxicity. Our results indicate that, while negatively charged QDs are relatively noncytotoxic compared to positively charged QDs, the same does not hold true for their genotoxic potential. Keeping QD core composition and size constant, 3 nm CdSe QD cores were functionalized with mercaptopropionic acid (MPA) or cysteamine (CYST), resulting in negatively or positively charged surfaces, respectively. CYST-QDs were found to induce significant cytotoxicity accompanied by DNA strand breakage. However, MPA-QDs, even in the absence of cytotoxicity and reactive oxygen species formation, also induced a high number of DNA strand breaks. QD-induced 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. Further, high-throughput real-time PCR analyses revealed upregulation of DNA damage and response genes and several proinflammatory cytokine genes. Most importantly, transcriptome sequencing revealed upregulation of the metallothionein family of genes in cells exposed to MPA-QDs but not CYST-QDs. These data indicate that cytotoxic assays must be supplemented with genotoxic analyses to better understand cellular responses and the full impact of nanoparticle exposure when making recommendations with regard to risk assessment.
authors.affiliation: Bioscience Division, ‡Center for Integrated Nanotechnologies, Materials Physics & Applications Division, and §Chemical Diagnostics and Engineering, Los Alamos National Laboratory , Los Alamos, New Mexico 87545, United States.
authors.forename: Amber
authors.initials: A
authors.lastname: Nagy
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hollingsworth
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Andrea
authors.initials: A
authors.lastname: Steinbrück
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stark
authors.forename: Cristina
authors.initials: C
authors.lastname: Rios Valdez
authors.forename: Momchilo
authors.initials: M
authors.lastname: Vuyisich
authors.forename: Michael H
authors.initials: MH
authors.lastname: Stewart
authors.forename: Donald H
authors.initials: DH
authors.lastname: Atha
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Nelson
authors.forename: Rashi
authors.initials: R
authors.lastname: Iyer
mesh_terms: D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D019187:Cadmium Compounds / Q000737:chemistry*; D002470:Cell Survival; D002478:Cells, Cultured; D004249:DNA Damage; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D045663:Quantum Dots; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry*
chemical_list: D019187:Cadmium Compounds; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; C058667:cadmium selenide