**1. Introduction**

High‐energy ionizing radiation (e.g., γ‐ and X‐rays, electrons, and ions) affects biological materials, via a chain of physical, chemical, and biological processes. A complete understand‐

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ing of these processes in living cells and tissues is a challenging task because of the multiple sequences of events, which lead to cell mutation or death. Nonetheless, such knowledge enhances our ability to cause death or inhibit growth of cancer cells in radiation therapy and to save healthy cells by radiation protection. As shown by many studies [1], cellular deoxyri‐ bose nucleic acid (DNA), containing genomic information, is the primary target for cell damage from ionizing radiation. The fundamental mechanisms involved in the induction of damage to DNA by radiation have therefore been subjects of intense investigations during the past decades [2, 3]. When exposed to ionizing radiation, large biomolecules such as DNA and proteins in the cell can be ionized and/or excited. This may effectively cause changes in their molecular structures by inducing bond ruptures and successive fragmentations, which then affect the function and metabolism of the cell. In DNA, the resulting damages may lead to incomplete repair, misrepair, or unrepair of the molecule. The displaced, mismatched, or damaged DNA bases may be misinterpreted during the replication cycle, deterring cell replications and causing accumulation of cancer predispositions for mutations [4–6].

Ionizing radiation damage to DNA can be induced directly by the interactions of primary quanta of radiation via ionization or excitation of individual components of the DNA itself and by secondary particles, including radicals, electrons, and ions generated along the track, after the interaction of primary radiation with molecules surrounding DNA, that is, water and other cellular components [7, 8]. It is by now well established that the consequences of radiation exposure of biological matter at the molecular level are largely due to secondary electrons (SEs), which are formed with a yield of about 5 × 104 per MeV of deposited radiation energy. SEs are the most abundant secondary species generated by the transfer of energy from ionizing radiation into the medium and essentially comprise slow electrons with kinetic energies below 30 eV. The energy distribution of SEs has a most probable energy around 9–10 eV [9], and those electrons of higher initial energy undergo successive energy losses via inelastic collisions, for example, electronic excitation and ionization. These later create further generations of electrons of significantly lower energies. As all electrons necessarily reach the low‐energy range (*E* < 30 eV), a detailed knowledge of reactions involving such low‐energy electrons (LEEs) with DNA is thus crucial to understand and accurately describe radiobiological damage. LEEs have been shown to induce genotoxic damage, for example, single‐ and double‐strand breaks (SSBs and DSBs) and other multiple damage sites by bond cleavage, chiefly through formation of a transient molecular anion (TMA) of DNA subunit, followed by dissociative electron attach‐ ment (DEA) or autoionization of TMA [10].

The main purpose of this chapter is to describe the phenomena related to reactions of LEEs, which may produce biological effects in the cell, such as apoptosis and cell cycle arrest. Since utmost of the harmful mutagenic and lethal damages of ionizing radiation result from chemical modifications in the nucleus of living cells, sustained studies have been focused on the ultrafast mechanisms involved in the direct interaction of LEEs with DNA and its different subunits, as well as indirect processes which are associated to the interactions of electrons with the principal cellular components nearby DNA. An ultimate understanding of LEE damage mechanisms and their role in DNA damage due to radiation can be obtained from experiments with molecular targets of increasing complexity, that is, from simple gaseous and condensed phase biomolecules to plasmid and cellular DNA. This wide range of target structures is essential to systematically understand how the fundamental principles of the LEE interaction with simple biomolecules and DNA components intervene in more complex ones up to and including cellular DNA [11].

ing of these processes in living cells and tissues is a challenging task because of the multiple sequences of events, which lead to cell mutation or death. Nonetheless, such knowledge enhances our ability to cause death or inhibit growth of cancer cells in radiation therapy and to save healthy cells by radiation protection. As shown by many studies [1], cellular deoxyri‐ bose nucleic acid (DNA), containing genomic information, is the primary target for cell damage from ionizing radiation. The fundamental mechanisms involved in the induction of damage to DNA by radiation have therefore been subjects of intense investigations during the past decades [2, 3]. When exposed to ionizing radiation, large biomolecules such as DNA and proteins in the cell can be ionized and/or excited. This may effectively cause changes in their molecular structures by inducing bond ruptures and successive fragmentations, which then affect the function and metabolism of the cell. In DNA, the resulting damages may lead to incomplete repair, misrepair, or unrepair of the molecule. The displaced, mismatched, or damaged DNA bases may be misinterpreted during the replication cycle, deterring cell

replications and causing accumulation of cancer predispositions for mutations [4–6].

ment (DEA) or autoionization of TMA [10].

180 Radiation Effects in Materials

Ionizing radiation damage to DNA can be induced directly by the interactions of primary quanta of radiation via ionization or excitation of individual components of the DNA itself and by secondary particles, including radicals, electrons, and ions generated along the track, after the interaction of primary radiation with molecules surrounding DNA, that is, water and other cellular components [7, 8]. It is by now well established that the consequences of radiation exposure of biological matter at the molecular level are largely due to secondary electrons (SEs), which are formed with a yield of about 5 × 104 per MeV of deposited radiation energy. SEs are the most abundant secondary species generated by the transfer of energy from ionizing radiation into the medium and essentially comprise slow electrons with kinetic energies below 30 eV. The energy distribution of SEs has a most probable energy around 9–10 eV [9], and those electrons of higher initial energy undergo successive energy losses via inelastic collisions, for example, electronic excitation and ionization. These later create further generations of electrons of significantly lower energies. As all electrons necessarily reach the low‐energy range (*E* < 30 eV), a detailed knowledge of reactions involving such low‐energy electrons (LEEs) with DNA is thus crucial to understand and accurately describe radiobiological damage. LEEs have been shown to induce genotoxic damage, for example, single‐ and double‐strand breaks (SSBs and DSBs) and other multiple damage sites by bond cleavage, chiefly through formation of a transient molecular anion (TMA) of DNA subunit, followed by dissociative electron attach‐

The main purpose of this chapter is to describe the phenomena related to reactions of LEEs, which may produce biological effects in the cell, such as apoptosis and cell cycle arrest. Since utmost of the harmful mutagenic and lethal damages of ionizing radiation result from chemical modifications in the nucleus of living cells, sustained studies have been focused on the ultrafast mechanisms involved in the direct interaction of LEEs with DNA and its different subunits, as well as indirect processes which are associated to the interactions of electrons with the principal cellular components nearby DNA. An ultimate understanding of LEE damage mechanisms and their role in DNA damage due to radiation can be obtained from experiments with molecular targets of increasing complexity, that is, from simple gaseous and condensed

In the first two sections of this chapter, the formation of TMAs and their decay into DEA and autoionization processes are extensively reviewed for simple molecules in the gas and condensed phases. The next section exclusively concerns the interactions of LEEs with basic DNA subunits, that is, the bases, the sugar–phosphate unit, and its two basic constituents in the gas phase. Such studies are necessary to understand how SSBs and DSBs and base release in the much more complex DNA molecule can occur by LEE impact. Additionally, gas‐phase DEA to radiosenisitizers (halogenated nucleobase, Pt‐ and nitrogen‐based compounds) is discussed in Section 4.

While most of the simple DNA building blocks can be readily vaporized for experimental study to the gas phase, most of the larger units, that is, nucleosides (containing a DNA base + sugar) and entire nucleotides (sugar + base + phosphate group) undergo decomposition during evaporation [12]. Electron attachment to the short oligonucleotides and single‐stranded oligomers containing different bases is reviewed in Section 5. Such molecules with a strong tendency to capture electrons and formation of electronically stable anions simplified the analysis of degradation products relative to longer single‐ and double‐stranded configurations [13]. Since histones and the other chromosomal proteins present in the nucleus are in close contact with DNA, reactive species resulting from the interactions of LEEs with nearby amino acids may also interact with DNA, causing indirect damage. There is thus considerable interest in studying the fragmentation of chromosomal proteins induced by LEEs [14], and Section 6 is devoted to the investigations of the action of LEEs on building blocks of proteins, more particularly on amino acids and peptides.

Despite the significance of the gas‐phase and condensed‐phase experiments in revealing the major interactions of LEE with DNA, the results of these experiments do not essentially correspond to those obtained in the dynamic existent situation of the cell, where cellular DNA lies in a medium containing essentially water with proteins, ions, and vitamins dissolved in the aqueous environment. Section 7 thus reviews recent studies in more complex systems, where a DNA molecule is embedded into more realistic environments containing water, oxygen, histones, and DNA‐binding proteins that mimic cellular conditions.

The role of secondary LEEs in radiosensitization and radiation therapy is discussed in the final section of this chapter. LEEs have subcellular ranges (on the order of 10 nm) in biological materials and interact strongly and destructively with chemical bonds; so, they are ideal for promoting local (i.e., nanoscopic) increases of radiation damage in cells, particularly for targeted cancer therapies. We review a wealth of experimental data on LEE‐induced lesions in DNA bound to radiosensitizing gold nanoparticles and the platinum‐chemotherapeutic agents. This final section links the effects of radiation and chemotherapy, showing that by modulating the radiation chemistry, chemotherapeutic agents can become radiosensitizers. It also explains how our fundamental understanding of LEE‐induced DNA damage can be applied to optimize concomitant chemoradiation therapy (CRT) by modifying the action of LEEs or by increasing their numbers in cancer cells.
