Damage induced in DNA and RNA components by low energy heavy ions, electrons and photons

Ion beams have recently emerged as a promising radiotherapy technique for treatment of large, solid, deep seated tumours. As the primary beam of heavy particles traverses through the cell, secondary charged and neutral species are generated. In particular secondary ions with energies up to 100 eV are produced in large numbers along the ionization track. Ionization and fragmentation of DNA components is a key step in radiobiological damage to the cell.;Ionization and fragmentation of Adenine (A), Guanine (G), Cytosine (C) and 5-aminouracil bases has been observed by low energy (10-100 eV) Ar + ions in the condensed phase and 70 eV electrons in the gas phase. These observations demonstrate fragmentation mechanisms involve site specific concerted dissociation reactions, deamination of Ade, Gua, Cyt in the condensed phase and the gas phase as well as amination of Adenine in the condensed phase. Of significant features of the mass spectra of all four bases are the production of NH4+ (18 amu) and CH3+ (15 amu) fragments with high intensities relative to the most intense peak in each spectrum (HCNH+, 28 amu). Utilizing isotopically labelled Ade, Gua and Cyt common purine and pyrimidine bond cleavage pathways and fragment origin sites were identified. Experiments performed with 5-aminouracil confirmed the deamination hypothesis of A, G and C bases by low energy Ar+ ion impact in the condensed phase as well as the low energy electron impact in the gas phase.;These results demonstrate induction of effective damage to the DNA by low energy heavy ions. Various physical and chemical mechanisms may involve initiation of this damage by fragmentation and ionization of DNA bases. In the gas phase, intra-molecular proton/hydrogen transfer may aide formation of NH4+, CH3+ and other intense fragments from within the base molecule. In the condensed phase however, adjacent base molecules may share a proton between two electron lone pairs. Ion desorption spectra of films of nucleobases suggest that intra/inter-molecular hydrogen transfer/proton tunnelling processes, tautomeric equilibrium and geometric characteristics of the nucleobases molecular structure and base stacking phenomena between nucleobases on different film layers may be responsible for emergence of masses 15 and 18 amu in the mass spectrum of all these bases.;Deamination of DNA base pairs occurs naturally in the cell a very low rate of 100-500 events per cell per day. Moreover enzymatic deamination has been observed in the genome of mammalian cells by enzymatic DNA deamination pathways. Chemical deamination processes may take place in the single strands of DNA, transforming Cytosine into Uracil, which upon replication implies a change of G into A in the opposite strand (and similar for deamination of A and G). The change induced can result in Transition mutation (also induced by amination of DNA bases). These results show that a process of physically induced deamination of DNA is mediated by hyperthermal heavy ion impact.;An ultrahigh vacuum (UHV) ion beam system has been used to study the ionization and fragmentation pathways of DNA bases by ion irradiation in the condensed phase and electron impact in the gas phase. The apparatus consists of a low energy ion source, beam line, biomolecular film preparation system and a reaction chamber with high-resolution mass spectrometer to monitor desorbing ion yields. Solid condensed films of DNA bases were prepared in vacuo by sample evaporation from an oven and were subsequently irradiated with (1-100 eV) Ar+ ions. Upon bombardment, desorbing positive and negative fragments were collected using a Quadrupole Mass Spectrometer (QMS).;Key words. heavy ion, low energy, deamination, proton tunnelling, condensed phase.