DEVELOPMENT OF A HYBRID MODEL TO QUANTIFY THE SINGLE AND DOUBLE STRAND BREAKS FOLLOWING THE IRON 57 DE-EXCITATION

The therapeutic utility of certain Auger emitters such as iodine-125 depends on their position within the cell nucleus. Or diagnostically, and to maintain as low as possible cell damage, it is preferable to have radionuclide localized outside the cell or at least the core. One solution to this problem is to consider markers capable of conveying anticancer drugs to the tumor site regardless of their location within the human body. The objective of this study is to simulate the impact of a complex such as bleomycin on single and double strand breaks in the DNA molecule. Indeed, this simulation consists of the following transactions: Construction of BLM -Fe- DNA complex, simulation of the electron’s transport from the metastable state excitation of Fe 57 by the Monte Carlo method, treatment of chemical reactions in the considered environment by the diffusion equation. For physical, physico-chemical and finally chemical steps, the geometry of the complex is considered as a sphere of 50 nm centered on the binding site , and the mathematical method used is called  step by step based on Monte Carlo codes. 
Keywords:

hybrid model,

___

  • Oudira H., Saifi A., "Quantification of the simple and double strand breaks following the disintegration of Iodine 125 in situ in chromosomal fiber", Radioprotection, vol. 45, pp. 389-408, 2010.
  • Panyutin I.G., Neuman R.D., "Sequence-specific DNA breaks produced by triplex directed decay of iodine 125", Acta oncologica, vol. 35(7), pp. 817-823, 1991.
  • Burger R.M., Peisach J. et Horuvitz S.B., "Activated bleomycin: Atransient complex of drug, iron and oxygen that degrades DNA", Biol.chem, vol. 256(22), pp. 11636-11644, 1981.
  • Absalon M.J., Stuble.J. et Kozarich J.W., "Sequence specific double-strand cleavage of DNA by Fe-Bleomycin.1. The detection of sequence specific double strand breaks using hairpin oligonucleotides", Biochemestry, vol. 52, pp. 2065-2075, 1995.
  • Terrissol M., Pomplum E., "Computer simulation of DNA incorporated I125 auger cascades and of the associated radiation chemistry", radiat, Prot. Dos., vol. 52, pp. 177-181, 1994.
  • Djamai D., Oudira H., Saifi A., "Application d’un modèle hybride à l’étude des dommages radio-induits par un faisceau d’électrons sur la molécule d’ADN dans son environnement", Radioprotection, vol. 43, pp. 357-387, 2008.
  • Oudira H., Djamai D., Saifi A., "Application d’un modèle déterministe à l’étude de l’influence des molécules radioprotectrices sur les rendements des cassures simple et double brin de la molécule d’ADN", Radioprotection, vol. 43, pp. 389-408, 2008.
  • W. Saenger., "Principles of nucleic acid structure", Ed. Springer-Verlag, New-York, 1984.
  • Widom J., Towae d., "a unified model of chromatin folding", Annu , Rev Biohys. Chem., vol. 81, pp. 365-395, 1989.
  • Vrigneaud J.M., Ph.D, "Développement d’un modèle biophysique pour l’évaluation des dommages radio-induits dans la fibre chromosomique", (Université, CPAT de Toulouse, 2000).
  • D.E. Charlton and J.L. Humm, "A method of calculating initial DNA strand breakage following the decay of incorporated I125", Int.J.Radiat.Biol, vol. 53, pp. 353-365, 1985.
  • Pomplum E., Booz.J. et Charlon.D.E., "A Monte Carlo simulation of Auger cascades", Rad.Res, vol. 111, pp. 533-552, 1987.