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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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CD spectra of pUC18 DNA.Notes: The interactions of pUC18 DNA with MAA and Cd–MAA were at a ratio of compound:DNA = 0.4. All the spectra were recorded in Tris-HCl buffer, pH 7.0.Abbreviations: CD, circular dichroism; MAA, mercaptoacetic acid; Cd-MAA, cadmium-mercaptoacetic acid.
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f7-ijn-7-2631: CD spectra of pUC18 DNA.Notes: The interactions of pUC18 DNA with MAA and Cd–MAA were at a ratio of compound:DNA = 0.4. All the spectra were recorded in Tris-HCl buffer, pH 7.0.Abbreviations: CD, circular dichroism; MAA, mercaptoacetic acid; Cd-MAA, cadmium-mercaptoacetic acid.

Mentions: Circular dichroism is a powerful technique to assess whether nucleic acids undergo conformational changes during drug–DNA interactions, as the bands arising from base stacking (275 nm) and from right-handed helicity (248 nm) are quite sensitive to the mode of DNA interactions with small molecules.28,29 In the CD spectra of pUC18 DNA that was treated with MAA and Cd–MAA (compound:DNA = 0.4:1) (Figure 7), the positive (275 nm) band decreased in intensity with the addition of the compound, while the negative (245 nm) band exhibited no significant change. This suggests that MAA and Cd–MAA can unwind the DNA helix and lead to the loss of helicity.30,31 The larger decrease in the CD band intensity, caused by Cd–MAA compared to MAA at the same concentration, implies that Cd–MAA is more effective than MAA in perturbing the secondary structure of DNA.


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)

CD spectra of pUC18 DNA.Notes: The interactions of pUC18 DNA with MAA and Cd–MAA were at a ratio of compound:DNA = 0.4. All the spectra were recorded in Tris-HCl buffer, pH 7.0.Abbreviations: CD, circular dichroism; MAA, mercaptoacetic acid; Cd-MAA, cadmium-mercaptoacetic acid.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368512&req=5

f7-ijn-7-2631: CD spectra of pUC18 DNA.Notes: The interactions of pUC18 DNA with MAA and Cd–MAA were at a ratio of compound:DNA = 0.4. All the spectra were recorded in Tris-HCl buffer, pH 7.0.Abbreviations: CD, circular dichroism; MAA, mercaptoacetic acid; Cd-MAA, cadmium-mercaptoacetic acid.
Mentions: Circular dichroism is a powerful technique to assess whether nucleic acids undergo conformational changes during drug–DNA interactions, as the bands arising from base stacking (275 nm) and from right-handed helicity (248 nm) are quite sensitive to the mode of DNA interactions with small molecules.28,29 In the CD spectra of pUC18 DNA that was treated with MAA and Cd–MAA (compound:DNA = 0.4:1) (Figure 7), the positive (275 nm) band decreased in intensity with the addition of the compound, while the negative (245 nm) band exhibited no significant change. This suggests that MAA and Cd–MAA can unwind the DNA helix and lead to the loss of helicity.30,31 The larger decrease in the CD band intensity, caused by Cd–MAA compared to MAA at the same concentration, implies that Cd–MAA is more effective than MAA in perturbing the secondary structure of DNA.

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