ABSTRACT
High and low LET radiation introduce the same types of DNA damages, and these include modifi cations to guanine, thymine, adenine and cytosine, single-strand breaks (SSBs), double-strand breaks (DSBs), abasic (AP) sites, deoxyribose damage and protein-DNA crosslinks (Teoule 1987; von Sonntag 1987; Oleinick 1987; Wallace 2002). DNA radicals generated by the direct deposition of energy in DNA are predicted to form in the proportion of 30% phosphate, 28% deoxyribose, 12% guanine, 11% adenine, 10% thymidine and 9% cytidine (Bernhard 2010). In cells, the lesions identifi ed in DNA are stable products that are produced following either the generation of DNA radicals (the direct effect) or the reaction of DNA with hydroxyl radicals (the indirect effect). Following irradiation of cells with gamma rays or carbon ions, the most prevalent base damage detected is thymidine glycol (cis and trans diastereoisomers) followed by 2,6-diamino-4-hydroxy-5formamidopyrimidine (FapyG). One of the most frequently studied lesions 8-oxo-7,8-dihydro-2’-deoxyguanosine (8oxodG), a base lesion often used as a biomarker of oxidative stress, is fourth on the list after 5-(hydroxymethyl)- 2’-deoxyuridine (Pouget et al. 2002; Cadet et al. 2003). Damage at the base can destabilize the N-glycosylic bond, resulting in loss of the base and generation of an abasic site in DNA. Specifi c damage to the deoxyribose sugar of DNA is due to the abstraction of hydrogen atoms and frequently results in strand breakage (von Sonntag 1987). The termini of radiationinduced strand breaks are modifi ed: all the 5’ termini and 70% of 3’ termini carry a phosphate group, while 30% of 3’ termini carry a phosphoglycolate group (Henner et al. 1983; Ward 1988). In terms of the yields of the different lesions, there is a ratio of 2.7 base damages generated per SSB (Ward 1995) for low LET radiation. This is in agreement with Monte Carlo simulations that estimated damage at 650 base damages Gy-1 giga basepairs (Gbp)–1 (including AP sites) and 217 strand breaks Gy-1 Gbp-1 (Semenko and Stewart 2006). DSB induction has been measured and is introduced at 4.2-6.9 DSBs Gy-1 Gbp-1 for low LET radiation (Prise et al. 1998), indicating that the yields of damages are in the order of base damage and AP sites > SSBs >> DSBs.
