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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 MAA-coated CdSe QDs on the plasmid DNA. (A) Electrophoresis in 1% agarose gel of pUC18 DNA (150 ng per sample) incubated for 2 hours at 4°C in the dark with QDs. Lane 1: pUC18 DNA only; lanes 2–6: pUC18 DNA incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L). (B) DNA quality of plasmids pUC18 incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L) for 2 hours at 4°C in the dark was tested by transformation with Escherichia coli strain DH5α. (C) Scanning densitometry results of three replicate experiments for each sample, with the error bars representing the standard deviations.Abbreviations: OC, opened circular; CCC, covalently closed circular; MAA, mercaptoacetic acid; QDs, quantum dots.
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f1-ijn-7-2631: Effects of MAA-coated CdSe QDs on the plasmid DNA. (A) Electrophoresis in 1% agarose gel of pUC18 DNA (150 ng per sample) incubated for 2 hours at 4°C in the dark with QDs. Lane 1: pUC18 DNA only; lanes 2–6: pUC18 DNA incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L). (B) DNA quality of plasmids pUC18 incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L) for 2 hours at 4°C in the dark was tested by transformation with Escherichia coli strain DH5α. (C) Scanning densitometry results of three replicate experiments for each sample, with the error bars representing the standard deviations.Abbreviations: OC, opened circular; CCC, covalently closed circular; MAA, mercaptoacetic acid; QDs, quantum dots.

Mentions: The damage caused by the MAA-coated CdSe QDs to the configuration of DNA was detected using agarose gel electrophoresis. The incubated plasmid DNA exhibited two bands on the agarose gel. The faster moving band corresponds to the CCC form, and the slower band corresponds to the OC form. Although DNA nicking could hardly be detected when the plasmid was incubated with low concentrations (0.4 μmol/L, 0.13 μmol/L, 0.043μmol/L) of MAA–QDs (lanes 4–6, Figure 1A), it was evident that the exposure of 833 ng of pUC18 DNA to high concentrations of QDs (3.6 μmol/L, 1.2 μmol/L) at 4°C for 2 hours in the dark resulted in DNA nicking (lanes 2–3, Figure 1A). The percentage of the OC form of plasmid DNA reached approximately 59.9% ± 12.8% at a concentration of 3.6 μmol/L QDs (Figure 1B), which indicated that the MAA-coated CdSe QDs are a potent DNA cleavage agent.


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 MAA-coated CdSe QDs on the plasmid DNA. (A) Electrophoresis in 1% agarose gel of pUC18 DNA (150 ng per sample) incubated for 2 hours at 4°C in the dark with QDs. Lane 1: pUC18 DNA only; lanes 2–6: pUC18 DNA incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L). (B) DNA quality of plasmids pUC18 incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L) for 2 hours at 4°C in the dark was tested by transformation with Escherichia coli strain DH5α. (C) Scanning densitometry results of three replicate experiments for each sample, with the error bars representing the standard deviations.Abbreviations: OC, opened circular; CCC, covalently closed circular; MAA, mercaptoacetic acid; QDs, quantum dots.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368512&req=5

f1-ijn-7-2631: Effects of MAA-coated CdSe QDs on the plasmid DNA. (A) Electrophoresis in 1% agarose gel of pUC18 DNA (150 ng per sample) incubated for 2 hours at 4°C in the dark with QDs. Lane 1: pUC18 DNA only; lanes 2–6: pUC18 DNA incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L). (B) DNA quality of plasmids pUC18 incubated with different concentrations of QDs (3.6, 1.2, 0.4, 0.13, 0.043 μmol/L) for 2 hours at 4°C in the dark was tested by transformation with Escherichia coli strain DH5α. (C) Scanning densitometry results of three replicate experiments for each sample, with the error bars representing the standard deviations.Abbreviations: OC, opened circular; CCC, covalently closed circular; MAA, mercaptoacetic acid; QDs, quantum dots.
Mentions: The damage caused by the MAA-coated CdSe QDs to the configuration of DNA was detected using agarose gel electrophoresis. The incubated plasmid DNA exhibited two bands on the agarose gel. The faster moving band corresponds to the CCC form, and the slower band corresponds to the OC form. Although DNA nicking could hardly be detected when the plasmid was incubated with low concentrations (0.4 μmol/L, 0.13 μmol/L, 0.043μmol/L) of MAA–QDs (lanes 4–6, Figure 1A), it was evident that the exposure of 833 ng of pUC18 DNA to high concentrations of QDs (3.6 μmol/L, 1.2 μmol/L) at 4°C for 2 hours in the dark resulted in DNA nicking (lanes 2–3, Figure 1A). The percentage of the OC form of plasmid DNA reached approximately 59.9% ± 12.8% at a concentration of 3.6 μmol/L QDs (Figure 1B), which indicated that the MAA-coated CdSe QDs are a potent DNA cleavage agent.

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