In situ evaluation of heavy metal-DNA interactions using an electrochemical DNA biosensor.

Heavy metal ions, lead, cadmium and nickel, are well known carcinogens with natural different origins and their direct mode of action is still not fully understood. A dsDNA-electrochemical biosensor, employing differential pulse voltammetry, was used for the in situ evaluation of Pb2+, Cd2+ and Ni2+ interaction with dsDNA. The results confirm that Pb2+, Cd2+ and Ni2+ bind to dsDNA, and that this interaction leads to different modifications in the dsDNA structure. These modifications were electrochemically recognized as changes in the oxidation peaks of guanosine and adenosine bases. Using homopolynucleotides of guanine and adenine it has been proved that the interaction between Pb2+ and DNA causes oxidative damage and preferentially takes place at adenine-containing segments, with the formation of 2,8-dihydroxyadenine, the oxidation product of adenine residues and a biomarker of DNA oxidative damage. The Pb2+ bound to dsDNA can still undergo oxidation. The interaction of Cd2+ and Ni2+ causes conformational changes, destabilizing the double helix, which can enable the action of other oxidative agents on DNA.

[1]  M. Fojta,et al.  Electrochemical Analysis of Nucleic Acids , 2002 .

[2]  Luigi Perbellini,et al.  Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C. , 2002, Mutation research.

[3]  Xianglin Shi,et al.  Conference overview: Molecular mechanisms of metal toxicity and carcinogenesis , 2005, Molecular and Cellular Biochemistry.

[4]  H. Kozłowski,et al.  Polarographic and spectroscopic study on Pb+2 Ion interaction with DNA , 1985 .

[5]  T. Simonsson,et al.  G-Quadruplex DNA Structures Variations on a Theme , 2001, Biological chemistry.

[6]  C. Brett,et al.  Step and Pulse Techniques , 2003 .

[7]  J. Justin Gooding,et al.  The electrochemical detection of cadmium using surface-immobilized DNA , 2007 .

[8]  V. Diculescu,et al.  Electrochemical behaviour of 2,8-dihydroxyadenine at a glassy carbon electrode. , 2007, Bioelectrochemistry.

[9]  M. Fojta Detecting DNA Damage with Electrodes , 2005 .

[10]  Teruhisa Tsuzuki,et al.  Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids , 2006, Biological chemistry.

[11]  A. Hartwig,et al.  Effect of cadmium(II) on the extent of oxidative DNA damage in primary brain cell cultures from Pleurodeles larvae. , 1998, Toxicology letters.

[12]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

[13]  A. Hartwig Carcinogenicity of metal compounds: possible role of DNA repair inhibition. , 1998, Toxicology letters.

[14]  A. M. Brett Electrochemistry for probing DNA damage , 2006 .

[15]  A. Hartwig,et al.  Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells. , 1997, Carcinogenesis.

[16]  Frieder W. Scheller,et al.  Electrochemistry of nucleic acids and proteins : towards electrochemical sensors for genomics and proteomics , 2005 .

[17]  H. Elżanowska,et al.  Complexation of bases and phosphates of nucleic acid components by transition metal ions , 1988 .

[18]  L. Poirier,et al.  Cadmium-induced 8-hydroxydeoxyguanosine formation, DNA strand breaks and antioxidant enzyme activities in lymphoblastoid cells. , 1997, Cancer letters.

[19]  J. Calzón,et al.  Electrocatalytic effects of deoxyribonucleic acids, adenine and guanine on the reduction of Ni(II) at a mercury electrode , 1998 .

[20]  L. Poirier,et al.  Are metals dietary carcinogens? , 1999, Mutation research.

[21]  Silvia H.P. Serrano,et al.  Electrochemical Oxidation of 8-Oxoguanine , 2000 .

[22]  Qingjun Liu,et al.  Detection of heavy metal toxicity using cardiac cell-based biosensor. , 2007, Biosensors & bioelectronics.

[23]  D. Averbeck,et al.  Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). , 2006, Biochimie.

[24]  Adsorption of synthetic homo- and hetero-oligodeoxynucleotides onto highly oriented pyrolytic graphite: atomic force microscopy characterization. , 2006, Biophysical chemistry.

[25]  F. Huq,et al.  Studies on the interaction between Cd(2+) ions and nucleobases and nucleotides. , 2002, Journal of inorganic biochemistry.

[26]  DNA-electrochemical biosensors for investigating DNA damage , 2007 .

[27]  E. Paleček,et al.  New trends in electrochemical analysis of nucleic acids , 1988 .

[28]  J. Światek REVIEW: INTERACTIONS OF METAL IONS WITH NUCLEIC ACIDS AND THEIR SUBUNITS. AN ELECTROCHEMICAL APPROACH , 1994 .

[29]  J. Séquaris,et al.  Interaction of DNA with Pb2+: Voltammetric and spectroscopic studies , 1991 .

[30]  Craig A. Grimes,et al.  Encyclopedia of Sensors , 2006 .

[31]  C. Brett,et al.  Nafion-coated mercury thin film electrodes for batch-injection analysis with anodic stripping voltammetry. , 1996, Talanta.

[32]  A. Oliveira‐Brett,et al.  Development of an HPLC method with electrochemical detection of femtomoles of 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine in the presence of uric acid. , 2004, Talanta.

[33]  Jane Anastassopoulou,et al.  Metal–DNA interactions , 2003 .

[34]  A. Hernanz,et al.  IR and Raman study on the interactions of the 5′-GMP and 5′-CMP phosphate groups with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II), Al(III) and Ga(III) , 2004, JBIC Journal of Biological Inorganic Chemistry.

[35]  M. Esteban,et al.  Cyclic voltammetry of metal/polyelectrolyte complexes: Complexes of cadmium and lead with deoxyribonucleic acid , 1990 .

[36]  H. Tajmir-Riahi,et al.  A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes. , 1988, Nucleic acids research.