Clustered DNA Damages induced by 0.5 to 30 eV Electrons

Abstract

Low-energy electrons (LEEs) of energies ≤30 eV are generated in large quantities by ionizing radiation. These electrons can damage DNA; particularly, they can induce the more detrimental clustered lesions in cells. This type of lesions, which are responsible for a large portion of the genotoxic stress generated by ionizing radiation, is described in the Introduction. The reactions initiated by the collisions of 0.5–30 eV electrons with oligonucleotides, duplex DNA, and DNA bound to chemotherapeutic platinum drugs are explained and reviewed in the subsequent sections. The experimental methods of LEE irradiation and DNA damage analysis are described with an emphasis on the detection of cluster lesions, which are considerably enhanced in DNA–Pt–drug complexes. Based on the energy dependence of damage yields and cross-sections, a mechanism responsible for the clustered lesions can be attributed to the capture of a single electron by the electron affinity of an excited state of a base, leading to the formation of transient anions at 6 and 10 eV. The initial capture is followed by electronic excitation of the base and dissociative attachment—at other DNA sites—of the electron reemitted from the temporary base anion. The mechanism is expected to be universal in the cellular environment and plays an important role in the formation of clustered lesions.

Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

“…The computational time of the simulation for a population of cells is also a big concern. MCTS codes are also not capable enough to reliably simulate the very low energy secondary electrons below about 10 eV, which are considered as potential lethal sources for the cell since they can induce harmful clustered lesions in the DNA [94,95].…”

Ultrafast Processes Occurring in Radiolysis of Highly Concentrated Solutions of Nucleosides/Tides

“…Although works from the late 70′s to date have established that radiation-produced electrons in their various stages exhibit different reactivity towards DNA subunits-bases and the sugar-phosphate backbone—this field is hence under active debate [4,8,29,30,31,38,39,45,56,57,58,59,60,61,62,63,64,70,71,72,73,74,75,88,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113]. The consensus that emerged from extensive studies by various groups are the following:…”

“…4 eV can induce SSBs in plasmid DNA via DEA. Recently, the Sanche group has provided evidence that LEEs (0.5 to 30 eV) can lead to clustered lesions [102]. Extensive experimental and theoretical studies have established that the initial step involves electron capture into the unoccupied molecular orbitals that are above the lowest unoccupied molecular orbitals (LUMOs) of the parent nucleobase.…”

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes

“…The type of damages induce by LEEs in DNA has been analyzed in detail by various techniques. It includes, base damage and cleavage, single and double strand breaks and other clustered lesions, consisting of strand breaks and base damages [11,[13][14][15][16]. Similar damages were observed and enhanced when GNPs were bound to DNA [17][18][19][20].…”