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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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ESI mass spectra of Cd(SCH2COOH)2 complex. Each peak represents an ion having a specific mass-to-charge ratio (m/z), and the height of the peak indicates the relative abundance. The base peak in the mass spectrum, corresponding to the ion which has the greatest intensity, is set to 100% relative abundance. (A) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the mixture of Cd and MAA. (B) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the solution of MAA-coated CdSe QDs. Cd(SCH2COOH)2 appears to be the primary toxin as no other ions were present above 10% relative abundance in either of the solutions.Abbreviations: ESI mass, electrospray ionization mass; MAA, mercaptoacetic acid.
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f5-ijn-7-2631: ESI mass spectra of Cd(SCH2COOH)2 complex. Each peak represents an ion having a specific mass-to-charge ratio (m/z), and the height of the peak indicates the relative abundance. The base peak in the mass spectrum, corresponding to the ion which has the greatest intensity, is set to 100% relative abundance. (A) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the mixture of Cd and MAA. (B) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the solution of MAA-coated CdSe QDs. Cd(SCH2COOH)2 appears to be the primary toxin as no other ions were present above 10% relative abundance in either of the solutions.Abbreviations: ESI mass, electrospray ionization mass; MAA, mercaptoacetic acid.

Mentions: Electrospray ionization mass spectrometry (ESI-MS) was performed to find the primary toxin in the mixture of Cd2+ and MAA. As a chelating agent, the ligand mercaptoacetic acid forms a CdL2 complex with cadmium chloride (Figure 5A) in the mixture of Cd and MAA. The Cd complex with mercaptoacetic acid could also be formed in the solution of MAA-coated CdSe QDs (Figure 5B). When incubated with pUC18 DNA, the Cd–MAA complex had a nicking effect on the plasmid DNA (data not shown). Furthermore, the configurational damage to plasmid pUC18 that was treated with non-sulfur compound coated QDs (OPA-QDs) was monitored, and no detectable DNA nicking was observed (data not shown). The biological damage to plasmid pUC18 treated with OPA-QDs was also monitored. The data indicated that the DNA was only slightly damaged when incubated with non-sulfur compound coated QDs (P > 0.05, Figure 2). Thus, in the case of MAA-coated CdSe QDs, we suggest that the DNA damage caused by MAA–QDs is a co-effect of the MAA and cadmium and that the Cd(SCH2COOH)2 complexes may be related to the DNA nicking. To the best of our understanding, the formation of the Cd–MAA complex in the solution of QDs and its effect on the secondary structure of DNA have not been comprehensively pursued in a systematic manner.


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)

ESI mass spectra of Cd(SCH2COOH)2 complex. Each peak represents an ion having a specific mass-to-charge ratio (m/z), and the height of the peak indicates the relative abundance. The base peak in the mass spectrum, corresponding to the ion which has the greatest intensity, is set to 100% relative abundance. (A) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the mixture of Cd and MAA. (B) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the solution of MAA-coated CdSe QDs. Cd(SCH2COOH)2 appears to be the primary toxin as no other ions were present above 10% relative abundance in either of the solutions.Abbreviations: ESI mass, electrospray ionization mass; MAA, mercaptoacetic acid.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368512&req=5

f5-ijn-7-2631: ESI mass spectra of Cd(SCH2COOH)2 complex. Each peak represents an ion having a specific mass-to-charge ratio (m/z), and the height of the peak indicates the relative abundance. The base peak in the mass spectrum, corresponding to the ion which has the greatest intensity, is set to 100% relative abundance. (A) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the mixture of Cd and MAA. (B) The base peak at m/z 146.8 suggests the greatest intensity of Cd(SCH2COOH)2 in the solution of MAA-coated CdSe QDs. Cd(SCH2COOH)2 appears to be the primary toxin as no other ions were present above 10% relative abundance in either of the solutions.Abbreviations: ESI mass, electrospray ionization mass; MAA, mercaptoacetic acid.
Mentions: Electrospray ionization mass spectrometry (ESI-MS) was performed to find the primary toxin in the mixture of Cd2+ and MAA. As a chelating agent, the ligand mercaptoacetic acid forms a CdL2 complex with cadmium chloride (Figure 5A) in the mixture of Cd and MAA. The Cd complex with mercaptoacetic acid could also be formed in the solution of MAA-coated CdSe QDs (Figure 5B). When incubated with pUC18 DNA, the Cd–MAA complex had a nicking effect on the plasmid DNA (data not shown). Furthermore, the configurational damage to plasmid pUC18 that was treated with non-sulfur compound coated QDs (OPA-QDs) was monitored, and no detectable DNA nicking was observed (data not shown). The biological damage to plasmid pUC18 treated with OPA-QDs was also monitored. The data indicated that the DNA was only slightly damaged when incubated with non-sulfur compound coated QDs (P > 0.05, Figure 2). Thus, in the case of MAA-coated CdSe QDs, we suggest that the DNA damage caused by MAA–QDs is a co-effect of the MAA and cadmium and that the Cd(SCH2COOH)2 complexes may be related to the DNA nicking. To the best of our understanding, the formation of the Cd–MAA complex in the solution of QDs and its effect on the secondary structure of DNA have not been comprehensively pursued in a systematic manner.

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