ABSTRACT
In this chapter, recent Ÿndings are presented that elaborate the free radical and molecular mechanisms of radiation damage to DNA. This chapter gives an overview of this area emphasizing recent Ÿndings. A series of previous reviews and books should be consulted for a more comprehensive understanding of the Ÿeld (Bernhard, 1981; Becker and Sevilla, 1993, 1998, 2008; Ward, 2000; Bernhard and Close, 2004; Sevilla and Becker, 2004; von Sonntag, 2006; Becker et al., 2007, 2010; Close, 2008; Kumar and Sevilla, 2008a). The Ÿndings covered in this chapter come from a variety of laboratories and lead to an improved understanding of the processes that lead to radiation-induced damage to DNA, beginning with initial energy deposition events, the subsequent formation of radical intermediates, and, ultimately, the formation of diamagnetic products and strand breaks. Although the physics of energy deposition of ionizing radiation and the eventual biologically signiŸcant endpoints have received substantial attention, it is the intervening radiation-induced free radical mechanisms and subsequent molecular product formation that have been less investigated and are the focus of this chapter. Direct-type effects of radiation on DNA are emphasized as these events account for about half the amount of the cellular DNA damage for low linear energy transfer (LET) radiation and become the dominant effect, as the LET of the radiation increases (Bernhard and Close, 2004; Sevilla and Becker, 2004; von Sonntag, 2006; Becker et al., 2007, 2010; Becker and Sevilla, 2008; Close, 2008). Direct-type effects include both the direct effect, which is the direct ionization of DNA, and the quasi-direct effects, which include those ionizations of the Ÿrst hydration shell and its near environment that transfer holes and non solvated electrons to DNA (Becker and Sevilla, 1993, 1998, 2008; Becker et al., 2007, 2010; Close, 2008). ESR studies suggest that the waters of hydration that contribute to the quasi-direct effect extend out to 9 or 10 waters per nucleotide (La Vere et al., 1996; Becker and Sevilla, 1998; Ward, 2000). The indirect effect of radiation chie¡y results from hydroxyl radicals produced from radiation damage to water molecules beyond 10 waters per nucleotide but still within a few nanometers of the DNA strand (O’Neill, 2001; von Sonntag, 2006). Electrons and a few hydrogen atoms formed on water ionization also contribute to the indirect effect (O’Neill, 2001; von Sonntag, 2006). The radiation-produced hydroxyl radicals are the chief damaging agent from the indirect effect (O’Neill, 2001; von Sonntag, 2006). However, each of the water radical species is
19.4.3 Strand Breaks and Damage Clusters from Heavy-Ion Direct Effects ...................... 521 19.4.4 Damage by Soft and Ultrasoft X-Rays ..................................................................... 522
19.5Excited States of Ion-Radicals as DNA Damage Precursors ............................................... 522 19.5.1Sugar-Phosphate Damage via Excited States of DNA Base Ion-Radicals .............. 522 19.5.2 Formation of One-Electron Oxidized Purines ......................................................... 523 19.5.3 Formation of Sugar Radicals .................................................................................... 525
19.5.3.1 Monomeric Model Compounds ................................................................. 525 19.5.3.2DNA-and RNA-Oligomers and DNA ....................................................... 527
19.5.4The Protonation State of One-Electron Oxidized 2′-Deoxyguanosine .................... 530 19.5.5 The Protonation State of One-Electron Oxidized Guanine
in dsDNA- Oligomers: The Role of Base Pairing ..................................................... 531 19.5.6 Factors Affecting the Sugar Radical Formation from Excitation
of Cation Radicals ................................................................................................ 533 19.5.6.1Site of Phosphate Substitution.................................................................... 533 19.5.6.2 Protonation State of One-Electron Oxidized Purine and pH .................... 533 19.5.6.3 Photoexcitation: Effect of Temperature ..................................................... 534 19.5.6.4 Wavelength of Photoexcitation................................................................... 534
19.6Conclusion ............................................................................................................................ 534 Acknowledgments .......................................................................................................................... 535 References ...................................................................................................................................... 535
largely scavenged by the high concentration of histone and other proteins in the DNA environment (Becker and Sevilla, 1993; Jones et al., 1993; O’Neill, 2001; von Sonntag, 2006).
