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Study on the genotoxic interaction of methyl violet with calf thymus DNA
Zhenxing Chi1, Rutao Liu, Xingchen Zhao
1School of Environmental Science and Engineering, Shandong University, 27# Shanda South Road, Jinan 250100, PR China.
Abstract:
By utilizing ultraviolet (UV)-visible absorption spectroscopy, circular dichroism (CD), resonance light scattering (RLS), and transmission electron microscope (TEM) techniques, the toxic interaction of methyl violet (MV) with calf thymus DNA (ctDNA) was investigated at the molecular level. The UV-visible absorption spectra results showed that MV intercalated into ctDNA base pairs at low MV concentrations, while MV was attached to the negative charged phosphate groups at higher concentrations and the binding constant (K(theta)(25 degrees C)) was 1.80 x 10(3) L mol(-1). The absorbency results showed that the genotoxic interaction of MV with ctDNA is under the electrostatic binding mode. MV had strong toxic interaction with ctDNA at 4.0 x 10(-5) mol L(-1) MV and pH 6.5. The toxic interaction of MV with ctDNA can result in the formation of massive aggregates and change of the ctDNA conformation, which showed a significant linear dose-response relationship.
Insights
Methyl violet (MV) interacts with calf thymus DNA (ctDNA) through intercalation at low concentrations and electrostatic binding at higher concentrations. This genotoxic interaction causes DNA aggregation and conformational changes, demonstrating a dose-response relationship.
Area of Science:
- Molecular Biology
- Toxicology
- Biophysics
Background:
- Methyl violet (MV) is a dye with known toxicological properties.
- Understanding its interaction with DNA is crucial for assessing genotoxicity.
- Calf thymus DNA (ctDNA) serves as a model for studying DNA-drug interactions.
Purpose of the Study:
- To investigate the molecular-level toxic interaction between methyl violet and calf thymus DNA.
- To elucidate the binding modes and quantify the binding affinity of MV to ctDNA.
- To determine the conditions favoring the genotoxic interaction between MV and ctDNA.
Main Methods:
- Ultraviolet (UV)-visible absorption spectroscopy
- Circular dichroism (CD)
- Resonance light scattering (RLS)
- Transmission electron microscopy (TEM)
Main Results:
- MV intercalates into ctDNA base pairs at low concentrations and binds electrostatically to phosphate groups at higher concentrations.
- The binding constant was determined to be 1.80 x 10(3) L mol(-1), indicating electrostatic binding.
- Strong toxic interaction occurred at 4.0 x 10(-5) mol L(-1) MV and pH 6.5, leading to DNA aggregation and conformational changes.
Conclusions:
- The genotoxic interaction between MV and ctDNA is primarily electrostatic.
- MV binding induces significant DNA aggregation and conformational alterations.
- A clear linear dose-response relationship exists for the toxic interaction of MV with ctDNA.
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