Pyrimidine Bases In DNA Research Articles

Genome-wide impact of cytosine methylation and DNA sequence context on UV-induced CPD formation.

Exposure to ultraviolet (UV) light is the primary etiological agent for skin cancers because UV damages cellular DNA. The most frequent form of UV damage is the cyclobutane pyrimidine dimer (CPD), which consists of covalent linkages between neighboring pyrimidine bases in DNA. In human cells, the 5' position of cytosine bases in CG dinucleotides is frequently methylated, and methylated cytosines in the TP53 tumor suppressor are often sites of mutation hotspots in skin cancers. It has been argued that this is because cytosine methylation promotes UV-induced CPD formation; however, the effects of cytosine methylation on CPD formation are controversial, with conflicting results from previous studies. Here, we use a genome-wide method known as CPD-seq to map UVB- and UVC-induced CPDs across the yeast genome in the presence or absence in vitro methylation by the CpG methyltransferase M.SssI. Our data indicate that cytosine methylation increases UVB-induced CPD formation nearly 2-fold relative to unmethylated DNA, but the magnitude of induction depends on the flanking sequence context. Sequence contexts with a 5' guanine base (e.g., GCCG and GTCG) show the strongest induction due to cytosine methylation, potentially because these sequence contexts are less efficient at forming CPD lesions in the absence of methylation. We show that cytosine methylation also modulates UVC-induced CPD formation, albeit to a lesser extent than UVB. These findings can potentially reconcile previous studies, and define the impact of cytosine methylation on UV damage across a eukaryotic genome.

Theoretical Study of Light-Induced Crosslinking Reaction Between Pyrimidine DNA Bases and Aromatic Amino Acids

Low-lying electronic excited states and their relaxation pathways as well as energetics of the crosslinking reaction between uracil as a model system for pyrimidine-type building blocks of DNA and RNA and benzene as a model system for aromatic groups of tyrosine (Tyr) and phenylalanine (Phe) amino acids have been studied in the framework of density functional theory. The equilibrium geometries of the ground and electronic excited states as well as the crossing points between the potential energy surfaces of the uracil–benzene complex were computed. Based on these results, different relaxation pathways of the electronic excited states that lead to either back to the initial geometry configuration or the dimerization between the six-membered rings of the uracil–benzene complex have been identified, and the energetic conditions for their occurrence are discussed. It can be concluded that the DNA–protein crosslinking reaction can be induced by the external electromagnetic field via the dimerization reaction between the six-membered rings of the uracil–benzene pair at the electronic excited-state level of the complex. In the case of the uracil–phenol complex, the configuration of the cyclic adduct (dimerized) conformation is less likely to be formed.

DNA pyrimidine bases in water: Insights into relative reactivity, byproducts formation and combined toxicity during chlorination

Soluble microbial products (SMPs), as precursors of disinfection byproducts (DBPs) in water treatment, are composed of polysaccharides, humic acid, proteins and DNA, and have caused widespread concerned. Pyrimidine bases (cytosine and thymine) are significant nitrogenous constituents of DNA, which could pose an adverse impact on water quality during chlorination. This study focused on the correlation between relative reactivity, formation of DBPs and combined toxicity in the chlorination of a binary pyrimidine base mixture. The relative reactivities of cytosine and thymine were quite different at a low disinfectant concentration; cytosine reacted more actively with chlorine than thymine did, at the chlorine/total pyrimidine bases molar ratio = 10. The chlorination of binary pyrimidine bases can produce both carbonous DBPs (C-DBPs) and nitrogenous DBPs (N-DBPs). In particular, the total yields of trichloromethane (TCM) and trichloronitromethane (TCNM) were lower than the additive yields of monadic cytosine and monadic thymine (“monadic” refers to “separate”), whereas the total yields of haloacetic acids (HAAs) and haloacetonitriles (HANs) were promoted evidently. High reactivity of cytosine with chlorine, greater potential of cytosine to produce specific DBPs and the alkylation of transformation products of thymine may synthetically account for the diversity in total DBPs yields, especially the increased formation of HAAs and HANs. In our toxicity trial, even though the antagonistic effect predominated at fa > 0.4 (fa refers to the affected fraction), the synergism at low concentration levels could enhance the combined toxicity by promoting the yields of N-DBPs.

The study of induction of 8-methoxypsoralen (8-MOP) SOS-response in bacteria Escherichia coli

8-Methoxypsoralen (8-MOP) is used for photochemotherapy of psoriasis and vitiligo. In therapy, called PUVA therapy, the affected skin of a patient who has previously been prescribed 8-MOP is irradiated with UV-A (> 320 nm). As a result of the photochemical reaction, 8-MOP forms a covalent bond with the pyrimidine bases of DNA and forms both monofunctional and bifunctional adducts. The latter cause 8-MOP-mediated cytotoxicity, leading to the death of psoriatic cells. However, in surviving cells, these same adducts can cause 8-MOP genotoxicity. For a comparative study of the cytotoxicity and genotoxicity of 8-MOP, the E. coli MG1655 lux biosensor (pColD-lux), carrying a recombinant plasmid with a lux operon controlled by the colD gene promoter, was first used. The colD gene (cda) is part of the E. coli SOS-regulon, which provides DNA repair and cell resistance to DNA damage. The death of bacteria was taken into account as an indicator of the cytotoxicity of 8-MOP+UV-A, and the death of bacteria was taken into account by the change in the luminescence intensity of the biosensor. Induction of 8-MOP-mediated SOS-response in bacteria depends on the dose of UV-A, and on the concentration of 8-MOP. At high UV-A doses, a 25-fold decrease in the survival of bacterial cells was detected (from 2 × 108 to 8 × 106 CFU), and in viable cells, an increase in the intensity of the SOS response by 675 times in terms of 106 cells. Thus, it was shown that in the bacterial test system, the genotoxic effect of 8-MOP is several times higher than its cytotoxicity. Key words: 8-methoxypsoralen, lux biosensor, E. coli, colD gene promoter, SOS response, UV radiation, adducts.

Effect of UV light on food quality and safety

Abstract The recent years have seen a great number of instances when ultraviolet (UV) radiation was used in the preservation process of all sorts of foods. Since the purine and pyrimidine bases of DNA and RNA absorb well the 254 nm radiation, its application with the use of a correct dosage can result in disinfections of various orders of magnitude. It can be particularly effective in cases where technology does not allow a more intensive heat treatment. When used properly, UV treatment can be a competitive procedure in the case of foodstuffs where the large surface area allows for UV rays to penetrate the entire volume of the substance. Incorrectly applied UV treatment may change the composition of foods. Free-radical as well as photochemical reactions can digest the proteins, damage the antioxidants, oxidize the lipids, make changes to the colour and substance, and produce undesirable flavourings and odorous substances. Some vitamins are particularly sensitive to UV irradiation in the course of which losses could reach even 50%. Photosensitive water-soluble vitamins are vitamin C, B12, B6, B2 and folic acid, while vitamins A, K and E are the fat soluble sensitive to light, carotene being the only provitamin with such properties. On the other hand, UV treatment can be a useful tool of food safety because of the photosensitivity of fungal toxins.

Implications of a Water Molecule for Photoactivation of Plant (6–4) Photolyase

Photolyases (PLs) are flavoproteins able to repair cross-links formed between adjacent pyrimidine bases in DNA in a light-dependent manner via an electron transfer. The catalytically active redox state of the flavin chromophore for the DNA repair is a fully reduced form of flavin adenine dinucleotide (FADH-). PLs and their relative, cryptochromes (CRYs), share a physicochemical process attributable to the light-dependent reduction of the chromophore via an ultrafast successive electron transfer through exclusively conserved three tryptophan side chains. In some (6-4) PLs and animal CRYs, an additional tryptophan participates in this photoactivation process. In a search for the intrinsic difference between the Trp triad and tetrad, a water molecule proximal to the second and third Trp was found in the reported crystal structure of Arabidopsis thaliana (6-4) PL. Here, we investigated the involvement of the water molecule in photoactivation. Molecular dynamics simulations indicated that the water molecule is stably captured in the binding site, while mutation of S412 increased water displacement from the binding site. Photochemical analysis of recombinant proteins revealed that the S412A mutation significantly decelerated the FAD photoreduction as compared to the wild type. The hydrogen-bonding network including the water molecule would play a key role in the stabilization of the FAD-Trp radical pair.

Design, synthesis and biological evaluation of novel trimethylangelicin analogues targeting nuclear factor kB (NF-kB)

A series of trimethylangelicin (TMA) derivatives were designed and synthesized to overcome the unwanted effects of TMA, promising agent for treatment of inflammation-related diseases and other pathologies, such as cystic fibrosis. The new generation TMA analogues bore hindered substituents at the 4 position in order to minimize or avoid the photoreactions with DNA. Among them, the 4-isopropyl-6-ethyl derivative 23 exhibited TMA-like inhibitory activity on NF-κB/DNA interactions but it proved unable to photoreact with pyrimidine bases of DNA, nor to induce any other DNA damage. The isopropyl analogue 23 was proven to lack mutagenicity when assayed through Ames test and exhibited no anti-proliferative activity on cystic fibrosis IB3-1 cells, displaying at the same time inhibition of the TNF-α induced release of the NF-κB regulated PDGF-B chain, IL-10, IL-15, IL-17 and IFN-γ. Therefore compound 23 deserves further assay to determine its anti-inflammatory properties, since it lacks photoreaction properties and mutagenicity-related side effects.

Kinetics and Thermodynamics of DNA Processing by Wild Type DNA-Glycosylase Endo III and Its Catalytically Inactive Mutant Forms.

Endonuclease III (Endo III or Nth) is one of the key enzymes responsible for initiating the base excision repair of oxidized or reduced pyrimidine bases in DNA. In this study, a thermodynamic analysis of structural rearrangements of the specific and nonspecific DNA-duplexes during their interaction with Endo III is performed based on stopped-flow kinetic data. 1,3-diaza-2-oxophenoxazine (tCO), a fluorescent analog of the natural nucleobase cytosine, is used to record multistep DNA binding and lesion recognition within a temperature range (5–37 °C). Standard Gibbs energy, enthalpy, and entropy of the specific steps are derived from kinetic data using Van’t Hoff plots. The data suggest that enthalpy-driven exothermic 5,6-dihydrouracil (DHU) recognition and desolvation-accompanied entropy-driven adjustment of the enzyme–substrate complex into a catalytically active state play equally important parts in the overall process. The roles of catalytically significant amino acids Lys120 and Asp138 in the DNA lesion recognition and catalysis are identified. Lys120 participates not only in the catalytic steps but also in the processes of local duplex distortion, whereas substitution Asp138Ala leads to a complete loss of the ability of Endo III to distort a DNA double chain during enzyme–DNA complex formation.

Analysis of the structures, energetics, and vibrational frequencies for the hydrogen-bonded interaction of nucleic acid bases with Carmustine pharmaceutical agent: a detailed computational approach

In the present study, it is attempted to scrutinize the hydrogen bonding interaction between Carmustine drug and DNA pyrimidine bases by means of density functional theory calculations regarding their geometries, binding energies, vibrational frequencies, and topological features of the electron density in the gas phase and the water solution. Based on the density functional theory results, it is found that the process of intermolecular interaction between Carmustine drug and nucleobases is exothermic and all of the optimized configurations are stable. Furthermore, the negative stability energy represented by a polarizable continuum model shows the significant increase in the solubility of the nucleobase after hydrogen bonding intermolecular interaction in the presence of water solvent. It is also found that the intermolecular hydrogen bonds between drug and the nucleobases play the significant role in the stability of the physisorption configurations. Hydrogen bond energies for hydrogen-bonded complexes are obtained from Espinosa method and the atoms-in-molecules theory are also applied to get a more precise insight into the nature of the intermolecular hydrogen bond interactions.

Electrochemical detection of DNA methylation using a glassy carbon electrode modified with a composite made from carbon nanotubes and β-cyclodextrin

We describe a method for detecting DNA methylation. It is based on direct oxidation of DNA bases at a glassy carbon electrode (GCE) modified with film of a multiwalled carbon nanotube-β-cyclodextrin composite. This nano-structured film causes a strong enhancement on the oxidation current of DNA bases due to its large effective surface area and extraordinary electronic properties. Well-defined peaks were obtained as a result of electro-oxidation of guanine (at 0.67 V), adenine (at 0.92 V), thymine (at 1.11 V), cytosine (at 1.26 V), and 5-methylcytosine (at 1.13 V; all data vs. saturated calomel electrode (SCE)). The potential difference between 5-methylcytosine and cytosine (130 mV) is large enough to enable reliable simultaneous determination and analysis. The interference by thymine can be eliminated by following the principle of complementary pairing between purine and pyrimidine bases in DNA. The modified electrode was successfully applied to the evaluation of 5-methylcytosine in a fish sperm DNA, the methylation level of cytosine was found to be 7.47 %, and the analysis process took less than 1 h.

Isomerization of 5-Hydroxy-5-methylhydantoin 2'-Deoxynucleoside into α-Furanose, β-Furanose, α-Pyranose, and β-Pyranose Anomers.

Oxidative damage is one of the most frequent types of DNA damage resulting from biologically generated oxygen or nitrogen reactive species. Hydroxyl radicals, one electron oxidants, and various chemical oxidants, such as permanganate and ozone, react with pyrimidine bases in DNA, cytosine and thymine, to produce 5-hydroxyhydantoin derivatives. 5-Hydroxyhydantoin modifications are interesting because they undergo ring-chain tautomerism into a pair of diastereomers via an open chain carbonyl intermediate. Here, we show that purified diastereomers of N1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin not only undergo isomerization into a mixture of 5R and 5S diastereomers of the hydantoin ring but also into three additional pairs of diastereomers, in which the sugar moiety transforms into α-furanose, β-pyranose, and α-pyranose anomers. The novel 5-hydroxy-5-methylhydantoin derivatives were characterized by extensive NMR analyses. Further studies indicate that isomerization is greatly suppressed at pH 6 compared to that at higher pH. A novel mechanism of isomerization is proposed to account for the formation of nucleoside anomers at neutral pH, which involves ring-chain tautomerism of both the hydantoin and sugar moieties. Last, the isomerization of β-furanose into the corresponding α-furanose is shown to take place in purified DNA, albeit to a slower extent than that in solution. The ability of 5-hydroxyhydantoin nucleosides to undergo isomerization may complicate the biological processing of this damage in cellular DNA.

Construction of 5‐amino‐1,10‐phenanthroline‐Fe(II) Nanostructures on Glassy Carbon Electrode: Simultaneous and Selective Determination of Purine and Pyrimidine DNA Bases

Abstract5‐amino‐1,10‐phenanthroline‐Fe(II) complex is immobilized onto GC electrode and used for determination of DNA bases. Modifications are traced by electrochemical methods. All DNA bases are electroactive on the modified electrode. The Ips increased linearly with increase of DNA bases concentration. A wide response range was observed for each base (∼4 orders for guanine (GA) and adenine (A); and ∼2.5 orders for thymine (T) and cytosine (C)) with DLs of 0.15, 4.44, 133.0 and 230.0 nM, respectively. The electrode was applied for determination of calf‐thymus DNA bases. The value obtained for [(GA+C)/(A+T)], 0.78, is in good agreement with standard value, 0.77.

Interactions of the 5-fluorouracil anticancer drug with DNA pyrimidine bases: a detailed computational approach

The H-bonded complexes formed from interaction between 5-fluorouracil (FU) and DNA pyrimidine bases have been investigated by B3LYP method using 6-311++G** basis set in the gas phase and the water solution. Vibrational frequencies and physical properties such as dipole moment, chemical potential, and chemical hardness of these compounds have been systematically explored. The natural bond orbital analysis and the Bader’s quantum theory of atoms in molecules are also used to elucidate the interaction characteristics of the investigated complexes. The aromaticity is measured using several well-established indices of aromaticity such as NICS, HOMA, PDI, ATI, and FLU. The MEP is given the visual representation of the chemically active sites and comparative reactivity of atoms. Furthermore, the effects of interactions on NMR data have been used for further investigation of the studied compounds.

Simultaneous determination of purine and pyrimidine bases in DNA using poly(3,4-ethylenedioxythiophene)/graphene composite film

A simple and reliable method for simultaneous determination of purine and pyrimidine (guanine, adenine, thymine and cytosine) was developed at poly(3,4-ethylenedioxythiophene)/electro-deposited graphene modified glassy carbon electrode (PEDOT/GR/GCE). Scanning electron microscopy and electrochemical impedance spectroscopy were used to examine the morphology and interface property of PEDOT/GR film. Differential pulse voltammetry was utilized to investigate the electrochemical behavior of DNA bases in 0.1M PBS (pH 7.4). The results showed that the peaks of four bases were well separated. The proposed sensor exhibited low detection limit, high sensitivity and wide linear range for simultaneous detection of four DNA bases, with high stability.

Effect of Ag(+) on the Excited-State Properties of a Gas-Phase (Cytosine)2Ag(+) Complex: Electronic Transition and Estimated Lifetime.

Recently, DNA molecules have received great attention because of their potential applications in material science. One interesting example is the production of highly fluorescent and tunable DNA-Agn clusters with cytosine (C)-rich DNA strands. Here, we report the UV photofragmentation spectra of gas-phase cytosine···Ag(+)···cytosine (C2Ag(+)) and cytosine···H(+)···cytosine (C2H(+)) complexes together with theoretical calculations. In both cases, the excitation energy does not differ significantly from that of isolated cytosine or protonated cytosine, indicating that the excitation takes place on the DNA base. However, the excited-state lifetime of the C2H(+) (τ = 85 fs), estimated from the bandwidth of the spectrum, is at least 2 orders of magnitude shorter than that of the C2Ag(+) (τ > 5000 fs). The increased excited-state lifetime upon silver complexation is quite unexpected, and it clearly opens the question about what factors are controlling the nonradiative decay in pyrimidine DNA bases. This is an important result for the expanding field of metal-mediated base pairing and may also be important to the photophysical properties of DNA-templated fluorescent silver clusters.

Selective Bond Cleavage in Potassium Collisions with Pyrimidine Bases of DNA

Electron transfer in alkali-molecule collisions to gas phase thymine and uracil yielding H- formation is selectively controlled in the energy range between 5.3 and 66.1 eV. By tuning the collision energy, electron transfer from the alkali to partly deuterated thymine, methylated thymine at the N1 and methylated uracil at the N3 positions, H- loss proceeds not only through the breaking of the (C-H) against (N-H) bonds but also through N1 against N3 sites. Such selectivity, as far as bond and site are concerned, is here reported for the first time by electron transfer induced dissociation experiments in alkali-molecule collisions.

Ab initio Calculation for Photochemistry of Psoralen Derivatives

Psoralens (Ps) are a class of heterocyclic aromatic compounds that have been extensively utilized in the photochemotherapy of skin disorders such as psoriasis and vitiligo, cutaneous T-cell lymphoma. On exposure to ultraviolet light, especially in the range of 320-400 nm, psoralens form chemical crosslinks to the DNA bases in the three steps. The first step is intercalation of psoralen between to adjacent base-pairs. The second step is formation of monoadduct; that is one psoralen molecule photo-react with one strand of DNA. The third step is the cross-linking of the same psoralen molecule to the other strand of DNA, thus covalently linking the two strand of a double stranded DNA. Psoralens have two photochemical reaction sites, 3,4pyrone double bond and 12,13-furan double bond, both of which are engaged in cross-linking of DNA bases. The formation of interstrand cross-linking through C4-cycloaddition of 3,4and 12,13-double bonds to the 5,6-double bond of the pyrimidine bases, especially thymine, in DNA has been correlated with the biological effects of photoexcited psoralens. Binding of Ps to DNA is generally the consequence of two successive events (1) intercalation into DNA between the base pairs; and (2) photocycloaddition reaction of 3,4Pyrone double bond and/or 12,13-furan double bond with 5,6-double bond of thymine. Although several photoproducts of purine bases from direct and photosensitized irradiation of purines are known, the photoaddition reaction between the excited psoralens and purine bases are not well understood. In the present paper, we report that the formation of interstrand cross-linking through C4-cycloaddition of 3,4and 12,13-double bonds to the 5,6-double bond of the pyrimidine bases, especially thymine, in DNA is calculated by the ab initio method. The molecular geometries are optimized at HF levels of theory with the 6-31G basis set by using the Gaussian 03 program. The 6-31G optimizations of the final structures are done to include the effect of electron correlation and the basis set with polarization function. The photosensitization activity of psoralens is generally correlated to their photoreactivity with pyrimidine bases in DNA. The cross-linkage is caused by the formation of cyclobutane adducts, which are produced by photoreactions of the psoralen 3,4-pyrone and 12,13-furan double bonds to two pyrimidine bases. The association energies for photocycloadduct (ΔE) are obtained by subtracting the sum of the energies of the 5MOP and two thymine from the energy of the full optimized photocycloadduct.

Abstract 2538: The anti-proliferative effect of PUVA treatment on human bladder cancer cell lines

Abstract Introduction and Objectives: Although immunotherapy and chemotherapy are the most used intravesical treatments for non-muscle-invasive bladder cancer (NMIBC), progression and recurrence rates are high. So far, several attempts have been done to hire a safer and more efficient treatment. Psoralen (a photoreactive chemical substance) metabolites followed by Ultra Violet A (UVA) irradiation (PUVA therapy) have been previously used to treat a variety of diseases. UVA radiation forms covalent bonds between psoralen molecule and pyrimidine bases of DNA to create interstrand cross-links, which blocks DNA replication, thereby inhibiting cell proliferation. In addition, PUVA therapy leads to apoptosis and local immune reaction. The aim of this study was to evaluate the anti-proliferative effects of PUVA treatment on human bladder cancer cell lines as the first step of further investigations, in order to consider it as a new candidate for NMIBC treatment. Material and Methods: Human bladder cancer cell lines (T24, grade III and RT4, grade I) were cultured in vitro, treated with 500 ng/ml 8-methoxypsoralen (8-MOP, a natural psoralen metabolite) and incubated in the dark room for 45 minutes. Cells were then irradiated with UVA (365 nm) at different doses (0, 0.5, 2 and 5 J/cm2). After 24- or 48-hour PUVA treatment, cells were counted to measure cell growth. MTT assay was performed in order to analyze cell viability and BrdU incorporation assay to evaluate the anti-proliferative effect of PUVA treatment. Cells were also stained with Annexin V-FITC and observed under fluorescence microscope in order to measure the amount of apoptotic cells. Results: Both T24 and RT4 cells treated with 2 and 5 J/cm2 UVA showed a significant decrease (P < 0.05) in the amount of cells after 24 hours, as compared to no UVA-treated cells. After 48 hours of PUVA treatment with all the three doses of UVA, the number of cells was significantly decreased in both cell lines. In MTT assay, PUVA-treated RT4 cells significantly reduced viability with 0.5, 2 and 5 J/cm2 UVA-treatments, as compared to no UVA-treatment. Differently, T24 cells showed a significant reduction of viability with only 5 J/cm2 UVA treatment. BrdU incorporation assay in both cell lines revealed a significant reduction of cell proliferation after PUVA treatment with all the three different UVA doses in comparison to no UVA treatment. Fluorescent microscopic observation of cell lines stained using Annexin V-FITC showed an increased number of apoptotic cells among those particularly treated with 2 and 5 J/cm2 UVA doses, as compared to no UVA-treated cells. Conclusions: PUVA treatment, mostly at higher UVA doses, has a significant anti-proliferative effect on human bladder cancer cell lines by inhibiting cell growth, reducing cell viability and inducing apoptosis. These results suggest a possible relevant use of PUVA therapy for the treatment of NMIBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2538. doi:10.1158/1538-7445.AM2011-2538

Electron paramagnetic resonance study of unpaired electron species in thin films of pyrimidine bases induced by nitrogen and oxygen K-shell photoabsorption

In order to clarify the mechanism of DNA-base modification induced by K-shell photoabsorption of nitrogen and oxygen atoms, we measured electron paramagnetic resonance (EPR) spectra of two DNA pyrimidine bases, thymine, and cytosine. The g-factor of 2.000 of the unpaired electron species arising only during irradiation is determined. The EPR intensities for cytosine are two times larger than those simply estimated based on the photoabsorption cross section, whereas those for thymine show similar energy dependence to photoabsorption spectra, suggesting that cytosine favors to form unpaired electron species, rather than thymine, presumably due to the excitation of the enhanced electron capturing.

SiC nanoparticles-modified glassy carbon electrodes for simultaneous determination of purine and pyrimidine DNA bases

For the first time a novel and simple electrochemical method was used for simultaneous detection of DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment or separation process. Glassy carbon electrode modified with silicon carbide nanoparticles (SiCNP/GC), have been used for electrocatalytic oxidation of purine (guanine and adenine) and pyrimidine bases (thymine and cytosine) nucleotides. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) techniques were used to examine the structure of the SiCNP/GC modified electrode. The modified electrode shows excellent electrocatalytic activity toward guanine, adenine, thymine and cytosine. Differential pulse voltammetry (DPV) was proposed for simultaneous determination of four DNA bases. The effects of different parameters such as the thickness of SiC layer, pulse amplitude, scan rate, supporting electrolyte composition and pH were optimized to obtain the best peak potential separation and higher sensitivity. Detection limit, sensitivity and linear concentration range of the modified electrode toward proposed analytes were calculated for, guanine, adenine, thymine and cytosine, respectively. As shown this sensor can be used for nanomolar or micromolar detection of different DNA bases simultaneously or individually. This sensor also exhibits good stability, reproducibility and long lifetime.