Radiation Damage to DNA: The Indirect Effect of Low-Energy Electrons

Abstract

We report the effect of DNA hydration level on damage yields induced by soft X-rays and photoemitted low energy electrons (LEEs) in thin films of plasmid DNA irradiated in N 2 at atmospheric pressure under different humidity levels. Contrary to a dilute solution of DNA, the number of H 2 O molecules per nucleotide (Γ) in these films can be varied from Γ=2.5 to ~33, where Γ≤20 corresponds to layers of hydration and Γ=33 to an additional bulk-like water layer. Our results indicate that DNA damage induced by LEEs does not increase significantly until the second hydration shell is formed. However, this damage increases dramatically as DNA coverage approaches bulk-like hydration conditions. A number of phenomena are invoked to account for these behaviors including: dissociative electron transfer from water-interface electron traps to CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptDNA bases, quenching of dissociative electron attachment to DNA and quenching of dissociative electronically excited states of H 2 O in contact with DNA. KeywordsDNA damage; strand breaks; humidity level; solvation; interface electronThe discovery that low energy electrons (LEEs, E<30 eV) can directly damage the DNA molecule with considerable efficiency 1,2,3 has established that almost all of the secondary electrons (SEs) produced by ionizing radiation can be lethal to the genome. 4 As a result, the new concepts that were developed during the studies of the mechanisms of action of LEEs 1,5 are starting to be applied to the development of new anti-cancer drugs 6,7,8 and the modification of clinical protocols. 9,10,11,12 Whereas the mechanisms of the direct action of LEEs on biomolecules are now fairly well understood, 4,5 the indirect effect of these electrons in irradiated cells remains unknown, owing essentially to the experimental difficulties associated with the production and observation of LEEs in aqueous media. Direct-type damage results from radiation energy being deposited directly into the DNA, whereas indirect damage occurs when the species created by the interaction of the primary radiation and SEs within the molecular environment surrounding the DNA (e.g., salts, proteins, oxygen and water) react with the molecule. 13,14 SEs with energies below 30 eV (i.e., LEEs) can attach to DNA components and thus form transient negative ions (TNIs) of DNA subunits (a base, sugar or phosphate group). In this manner, LEEs induce direct damage to DNA, such as single and double strand breaks (SSBs and DSBs) principally via the decay of TNIs into dissociating electronically excited states and dissociative electron attachment (DEA). 4,15 Since cells contain 70-80% water, 16 LEEs also react with water molecules near DNA in the cell nucleus and create reactive species to produce indirect damage.To estimate the relative contribution of the indirect and direct modes of damage of LEEs in cells, experiments were undertaken with thin films of short single DNA strands (i.e., oligonucleotides) embedded into biomolecular enviro...

Understanding the Interaction between Low-Energy Electrons and DNA Nucleotides in Aqueous Solution

“…Structural waters appear to reduce the damage, 13 while adding bulk water increases the damage done by LEEs. 12 These water molecules can affect the damage process by (a) modifying the effective potential felt by the excess electron and (b) influencing the dynamics of any dissociated fragments.…”

Evaluating experimental molecular physics studies of radiation damage in DNA*

“…When the cellular environment is being investigated in the close proximity to DNA at the nanometric scale, it should be considered as an extremely concentrated solution, where all the suspended molecules play an important role in the secondary damage. Therefore, it is vital to investigate the interactions and damage mechanism between low energy electrons and DNA [34].…”

“…The topic of DEA to biomolecules has also been extensively reviewed by the experts in this topic [14,34,48,49].…”

Hydrated Electron Transfer to Nucleobases in Aqueous Solutions Revealed by Ab Initio Molecular Dynamics Simulations

“…[3,[11][12][13][14][15][16][17][18][19] Furthermore, the reactivity of EEs with DNA was also conducted withd ry DNA or DNA in more realistic biological environments (e.g. sparse water,s alts, and proteins).…”