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The cadmium-mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots.

Tang W, Fan J, He Y, Huang B, Liu H, Pang D, Xie Z - Int J Nanomedicine (2012)

Bottom Line: Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes.However, the genotoxicity potential of QDs still remains unclear.The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium-mercaptoacetic acid complex (Cd-MAA) that is formed in the solution of MAA-QDs.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.

ABSTRACT
Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA-QDs) were investigated. After incubation with different concentrations of MAA-QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA-QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium-mercaptoacetic acid complex (Cd-MAA) that is formed in the solution of MAA-QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd-MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.

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Effects of QDs on the plasmids with different GC contents.Notes: Plasmids with the same size and dose but contained different GC contents (41.5%, 59.55%) and were incubated with MAA-coated CdSe QDs (3 μmol/L) for 2 hours at 4°C in the dark. P < 0.001.Abbreviations: QDs, quantum dots; GC content, guanine + cytosine content.
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f8-ijn-7-2631: Effects of QDs on the plasmids with different GC contents.Notes: Plasmids with the same size and dose but contained different GC contents (41.5%, 59.55%) and were incubated with MAA-coated CdSe QDs (3 μmol/L) for 2 hours at 4°C in the dark. P < 0.001.Abbreviations: QDs, quantum dots; GC content, guanine + cytosine content.

Mentions: Groove-binding compounds, such as the Cu–methyl thiophanate complex and amsacrine, prefer binding to the AT-rich region or to poly(dA-dT).24,26,32 Therefore, DNA containing higher contents of AT could receive more damage from the groove-binding compounds. To examine whether the Cd–MAA complex is a groove-binding compound, experiments evaluating the biological damage to plasmids with different GC percentage (41.5%, 59.55%) were performed. After incubation with the same concentration of MAA–QDs (3.6 μmol/L) at 4°C for 12 hours in the dark, a significantly higher residual transformation activity of the high GC% plasmid was observed compared to the low GC% one (P < 0.001, Figure 8), indicating that the Cd–MAA complex is a groove-binding compound and has an innate tendency to damage plasmids with high content of AT.


The cadmium-mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots.

Tang W, Fan J, He Y, Huang B, Liu H, Pang D, Xie Z - Int J Nanomedicine (2012)

Effects of QDs on the plasmids with different GC contents.Notes: Plasmids with the same size and dose but contained different GC contents (41.5%, 59.55%) and were incubated with MAA-coated CdSe QDs (3 μmol/L) for 2 hours at 4°C in the dark. P < 0.001.Abbreviations: QDs, quantum dots; GC content, guanine + cytosine content.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368512&req=5

f8-ijn-7-2631: Effects of QDs on the plasmids with different GC contents.Notes: Plasmids with the same size and dose but contained different GC contents (41.5%, 59.55%) and were incubated with MAA-coated CdSe QDs (3 μmol/L) for 2 hours at 4°C in the dark. P < 0.001.Abbreviations: QDs, quantum dots; GC content, guanine + cytosine content.
Mentions: Groove-binding compounds, such as the Cu–methyl thiophanate complex and amsacrine, prefer binding to the AT-rich region or to poly(dA-dT).24,26,32 Therefore, DNA containing higher contents of AT could receive more damage from the groove-binding compounds. To examine whether the Cd–MAA complex is a groove-binding compound, experiments evaluating the biological damage to plasmids with different GC percentage (41.5%, 59.55%) were performed. After incubation with the same concentration of MAA–QDs (3.6 μmol/L) at 4°C for 12 hours in the dark, a significantly higher residual transformation activity of the high GC% plasmid was observed compared to the low GC% one (P < 0.001, Figure 8), indicating that the Cd–MAA complex is a groove-binding compound and has an innate tendency to damage plasmids with high content of AT.

Bottom Line: Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes.However, the genotoxicity potential of QDs still remains unclear.The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium-mercaptoacetic acid complex (Cd-MAA) that is formed in the solution of MAA-QDs.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.

ABSTRACT
Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA-QDs) were investigated. After incubation with different concentrations of MAA-QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA-QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium-mercaptoacetic acid complex (Cd-MAA) that is formed in the solution of MAA-QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd-MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.

Show MeSH
Related in: MedlinePlus