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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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Competitive displacement of intercalating dye EtBr from EtBr-CT-DNA complex by the Cd–MAA complex.Notes: Curves from top to bottom: EtBr (10 μmol/L) +CT-DNA (50 μmol/L); EtBr (10 μmol/L) +CT-DNA (50 μmol/L) +cadmium complex (10, 20, 30, 40, 50, 100, 1000 μmol/L). Fluorescence was monitored at 605 nm using an excitation wavelength of 518 nm.Abbreviations: EtBr, ethidium bromide; CT-DNA, Calf-thymus DNA; Cd-MAA, cadmium-mercaptoacetic acid.
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f6-ijn-7-2631: Competitive displacement of intercalating dye EtBr from EtBr-CT-DNA complex by the Cd–MAA complex.Notes: Curves from top to bottom: EtBr (10 μmol/L) +CT-DNA (50 μmol/L); EtBr (10 μmol/L) +CT-DNA (50 μmol/L) +cadmium complex (10, 20, 30, 40, 50, 100, 1000 μmol/L). Fluorescence was monitored at 605 nm using an excitation wavelength of 518 nm.Abbreviations: EtBr, ethidium bromide; CT-DNA, Calf-thymus DNA; Cd-MAA, cadmium-mercaptoacetic acid.

Mentions: Ethidium bromide (EtBr) fluorescence displacement experiments were employed to further investigate the interaction mode between the cadmium complex and DNA. The assay was based on the theory that a highly fluorescent complex could be formed between native DNA and the intercalating agent, EtBr. Using CT-DNA as a model, the damage to DNA caused by the cadmium complex was explored using the fluorescence method. The binding of the cadmium complex to CT-DNA was studied by evaluating the fluorescence emission intensity of the EtBr–DNA system following addition of the compound. In our experiment, as illustrated in Figure 6, the fluorescence intensity at 605 nm of EtBr bound to DNA showed no significant decreasing trend with increasing concentrations of the cadmium complex, which is suggestive of a nonintercalative mode of DNA binding. By considering the fluorescence intensity value of EtBr-DNA complexes as equal to 100%, the extent of fluorescence quenching with the Cd–MAA complex has been determined to be equal to 20.21% at the highest molar ratio of 1:20. Furthermore, similar fluorescence quenching effects of EtBr bound to DNA have been observed for the addition of several groove-binding compounds, including distamycin A, methyl thiophanate, and amsacrine.24–26 This observation leads us to suggest that the cadmium complex may interact with DNA through the groove-binding mode.27


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)

Competitive displacement of intercalating dye EtBr from EtBr-CT-DNA complex by the Cd–MAA complex.Notes: Curves from top to bottom: EtBr (10 μmol/L) +CT-DNA (50 μmol/L); EtBr (10 μmol/L) +CT-DNA (50 μmol/L) +cadmium complex (10, 20, 30, 40, 50, 100, 1000 μmol/L). Fluorescence was monitored at 605 nm using an excitation wavelength of 518 nm.Abbreviations: EtBr, ethidium bromide; CT-DNA, Calf-thymus DNA; Cd-MAA, cadmium-mercaptoacetic acid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368512&req=5

f6-ijn-7-2631: Competitive displacement of intercalating dye EtBr from EtBr-CT-DNA complex by the Cd–MAA complex.Notes: Curves from top to bottom: EtBr (10 μmol/L) +CT-DNA (50 μmol/L); EtBr (10 μmol/L) +CT-DNA (50 μmol/L) +cadmium complex (10, 20, 30, 40, 50, 100, 1000 μmol/L). Fluorescence was monitored at 605 nm using an excitation wavelength of 518 nm.Abbreviations: EtBr, ethidium bromide; CT-DNA, Calf-thymus DNA; Cd-MAA, cadmium-mercaptoacetic acid.
Mentions: Ethidium bromide (EtBr) fluorescence displacement experiments were employed to further investigate the interaction mode between the cadmium complex and DNA. The assay was based on the theory that a highly fluorescent complex could be formed between native DNA and the intercalating agent, EtBr. Using CT-DNA as a model, the damage to DNA caused by the cadmium complex was explored using the fluorescence method. The binding of the cadmium complex to CT-DNA was studied by evaluating the fluorescence emission intensity of the EtBr–DNA system following addition of the compound. In our experiment, as illustrated in Figure 6, the fluorescence intensity at 605 nm of EtBr bound to DNA showed no significant decreasing trend with increasing concentrations of the cadmium complex, which is suggestive of a nonintercalative mode of DNA binding. By considering the fluorescence intensity value of EtBr-DNA complexes as equal to 100%, the extent of fluorescence quenching with the Cd–MAA complex has been determined to be equal to 20.21% at the highest molar ratio of 1:20. Furthermore, similar fluorescence quenching effects of EtBr bound to DNA have been observed for the addition of several groove-binding compounds, including distamycin A, methyl thiophanate, and amsacrine.24–26 This observation leads us to suggest that the cadmium complex may interact with DNA through the groove-binding mode.27

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