title: Is coulomb explosion a damaging mechanism for (125)IUdR?
abstract: OBJECTIVE
  To test the integrity of the thymine molecule that experiences an increasing number of charges due to the loss of Auger electrons emitted by the decay of incorporated 125I. Besides the radiation action of these electrons, Coulomb explosion is suspected to be an additional mechanism responsible for the strong radiotoxic effect of decaying DNA-incorporated 125I. The two-step decay process initiates a first Auger cascade within 10(-16) to 10(-14) s resulting in the release of about 7 electrons on average and a corresponding large positive charge on the 125Te daughter atom. Being part of iododeoxyuridine (125IUdR), the analogue of the DNA base thymine, the base is suddenly confronted with this charge. Experimentally, the situation was investigated with small molecules (CH3(125)I and C2H5(125)I) resulting in ion fragmentation in agreement with a Coulomb explosion model (Carlson and White, 1963, 1966).
  
  
  METHODS
  Semi-empirical quantum mechanical calculations on the Parametric Method 3 (PM3) level (Stewart, 1989a, 1989b) were performed and geometry optimisation was applied for the identification of stable molecule conformations. Subsequently, semiempirical molecular dynamics simulations allowed changes in the conformations to be studied as a function of time.
  
  
  RESULTS
  First results show that there is no stable molecular configuration with a total charge of > or = +5e. PM3 calculations will not converge for such a charge located at the 125I/125Te position. This finding is supported by total energy considerations, which begin to favour a system of isolated atoms versus molecular bound atoms when the molecular charge is greater than +4e. The distribution of the partial charges indicates that most of the charge will remain on the tellurium atom with slight increases of charge at the other molecular partners within 125IUdR. Moreover, the molecular dynamics simulations reveal a breaking of chemical bonds between those atoms with the strongest charge increase.
  
  
  CONCLUSIONS
  Coulomb explosion must be taken into account as a possible damaging mechanism following the decay of DNA-incorporated Auger electron emitters. Lobachevsky and Martin (2000) have identified the same mechanism to be responsible for part of strand breakage in oligo-deoxynucleotides. To elucidate a possible link between both damage patterns the molecular mechanics simulations have to be extended to larger parts of the DNA molecule.
authors.affiliation: Department for Safety and Radiation Protection, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany. e.pomplun@fz-juelich.de
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Pomplun
authors.forename: Godehard
authors.initials: G
authors.lastname: Sutmann
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004583:Electrons / Q000009:adverse effects; D007065:Idoxuridine / Q000737:chemistry* / Q000528:radiation effects*; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000528:radiation effects; D011829:Radiation Dosage; D055672:Static Electricity
chemical_list: D004247:DNA; D007065:Idoxuridine