title: DNA melting and genotoxicity induced by silver nanoparticles and graphene.
abstract: We have revealed a connection between DNA-nanoparticle (NP) binding and in vitro DNA damage induced by citrate- and branched polyethylenimine-coated silver nanoparticles (c-AgNPs and b-AgNPs) as well as graphene oxide (GO) nanosheets. All three types of nanostructures triggered an early onset of DNA melting, where the extent of the melting point shift depends upon both the type and concentration of the NPs. Specifically, at a DNA/NP weight ratio of 1.1/1, the melting temperature of lambda DNA dropped from 94 °C down to 76 °C, 60 °C, and room temperature for GO, c-AgNPs and b-AgNPs, respectively. Consistently, dynamic light scattering revealed that the largest changes in DNA hydrodynamic size were also associated with the binding of b-AgNPs. Upon introduction to cells, b-AgNPs also exhibited the highest cytotoxicity, at the half-maximal inhibitory (IC50) concentrations of 3.2, 2.9, and 5.2 mg/L for B and T-lymphocyte cell lines and primary lymphocytes, compared to the values of 13.4, 12.2, and 12.5 mg/L for c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets, respectively. At cytotoxic concentrations, all NPs elicited elevated genotoxicities via the increased number of micronuclei in the lymphocyte cells. However, b-AgNPs also induced micronuclei at subtoxic concentrations starting from 0.1 mg/L, likely due to their stronger cellular adhesion and internalization, as well as their subsequent interference with normal DNA synthesis or chromosome segregation during the cell cycle. This study facilitates our understanding of the effects of NP chemical composition, surface charge, and morphology on DNA stability and genotoxicity, with implications ranging from nanotoxicology to nanobiotechnology and nanomedicine.
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Mawson Institute, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Ivask
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Mawson Institute, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia.
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Voelcker
authors.affiliation: ‡CSIRO Manufacturing Flagship, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Seabrook
authors.affiliation: §CSIRO Health Sciences and Nutrition Flagship, Kintore Avenue, Adelaide SA 5000, Australia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hor
authors.affiliation: ∥CSIRO Land and Water Flagship, Waite Road-Gate 4, Glen Osmond, SA 5064, Australia.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kirby
authors.affiliation: §CSIRO Health Sciences and Nutrition Flagship, Kintore Avenue, Adelaide SA 5000, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
authors.affiliation: ⊥ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.|#Department of Chemistry, Warwick University, Gibbet Hill, Coventry, CV4 7AL, United Kingdom.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
authors.affiliation: ⊥ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Pu Chun
authors.initials: PC
authors.lastname: Ke
mesh_terms: D010582:Bacteriophage lambda / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D019169:Jurkat Cells; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009691:Nucleic Acid Denaturation / Q000187:drug effects*; D012834:Silver / Q000633:toxicity*
chemical_list: D004279:DNA, Viral; D009153:Mutagens; D012834:Silver; D006108:Graphite; D004247:DNA