Mechanisms of DNA damage induced by low energy (0-20 eV) electrons

Mechanisms of DNA damage induced by low energy (0-20 eV) electrons

Secondary electrons are the most abundant species produced by high energy radiation, and by far, most of them have energies below 20 eV. These low energy electrons (LEEs) play a significant role in the mechanisms leading to radiobiological damage, particularly in radiotherapy, and its sensitization by chemotherapeutic drugs and nanoparticles.¹ LEEs are  also implicated in radiation protection on earth and in space. Despite their significant role in these fields and particularly in nanoscale therapy using targeted radiation sources,² understanding their behavior within cells remains a considerable experimental and theoretical challenge. Considering that DNA is the most critical molecule leading to cellular radiation damage, I will first give a general overview of our present understanding of LEE-DNA interactions, and afterward, dwell into the problem of calculating the biological effects of LEEs in cellular media via Monte Carlo (MC) codes. Applying such codes successfully should allow to derive the biological effectiveness of radiation of any source in any geometry. 
LEEs usually interact with biomolecules via a resonance process, which involves the temporary capture of an electron in an unfilled orbital, leading to the formation of a transient anion (TA).¹ TAs have lifetimes varying from about one femtosecond to picoseconds and can efficiently break chemical bonds by dissociating, a process called dissociative electron attachment (DEA), or by autoionization, which can leave the neutral molecule in a dissociative excited state. In DNA, TAs usually form on nucleobases, where they can induce base damage or transfer the extra electron to the phosphate group to produce a single strand break via DEA^1,3. Cluster lesions (e.g., double strand breaks), which are highly detrimental to cells, can be created when an autoionizing electron leaving a base in a dissociative excited state is transferred to another subunit where DEA occurs¹. Furthermore, the magnitude of these phenomena is subjected to electron diffraction in the DNA strands that changes with their length.
The main obstacle encountered to introduce LEEs in established MC codes lies in their treatment of an electron as a classical particle interacting with matter at a specific point in space-time, i.e., the wave behavior of LEEs is neglected as well as the time delay caused by the formation of TAs. The use of absolute cross sections, to introduce in such codes LEE-induced damages to DNA will be discussed.
 
1. Gao, Y.; Zheng, Y.; Sanche, L. Low-Energy Electron Damage to Condensed-Phase DNA and Its Constituents. Int. J. Mol. Sci. 2021, 22, 7879.
2. Khosravifarsani, M.; Ait-Mohand, S.; Paquette, B.; Sanche, L.; Guérin, B. High Cytotoxic Effect by Combining Copper-64 with a NOTA–Terpyridine Platinum Conjugate. J. Med. Chem. 2021, 64, 6765–6776.
3. Boudaiffa, B.; Cloutier, P.; Hunting, D.; Huels, M.A.; Sanche, L. Resonant formation of DNA strand breaks by low energy (3-20 eV) electrons. Science 2000, 287, 1658-1660.