radiation, free radical generation, subcellular radiogenic damage

Figure 17.1A). The initially ejected electrons (e) may possess sufficient energy themselves to cause further ionizations until their energy is dissipated and they become solvated to give an aqueous electron (eaq) and/or combine with other species to generate reducing species such as hydrogen atoms (H) or superoxide (O2•−). Ionizing radiation is non-discriminatory in that all molecular species in a cell may be damaged. However, DNA is considered to be a key molecular target for the deleterious effects of ionizing radiation in cells. OH radicals are highly reactive and, together with the less reactive reducing species, may damage DNA via the so-called indirect effect (Figure 17.1A). Radiation can also directly ionize the DNA leading to direct damage of the DNA’s bases or sugar-phosphate backbone (R+•) (Figure 17.1B); although the distinction between direct and indirect damage is not always clear as electrons and radical cations produced in the DNA and DNA-associated water may lead to further ionizations/oxidations in the DNA macromolecule and its surrounding microenvironment.


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Figure 17.1 The (A) indirect and (B) direct effects of ionizing radiation. In the indirect effect, radiation interacts with water to produce hydroxyl free radicals (OH) which, in turn, react with the DNA producing damage. In the direct effect, the radiation interacts directly with the DNA to produce damage. While both direct and indirect effects damage DNA, it is suggested that only indirect events happening within 2   nm of the DNA damage the DNA. Indirect effects dominate for low LET ionizing radiations. (The ‘dot’ refers to an unpaired electron of a free radical, and the dashed lines reflect the lower reactivity of the reducing species with DNA, as compared to the high reactivity of OH).


Through direct and indirect effects, radiation causes a wide range of damage in DNA, including strand breaks, base or sugar damage and cross-links between macromolecules (i.e. DNA–DNA or DNA–protein cross-links) (Figure 17.2A); the frequency of these DNA lesions is shown in Table 17.1. In general, it is considered that the DNA double-strand break (DSB) is the most critical for the lethal effects of radiation; evidence for this is a follows:



under a variety of experimental conditions, it is the relative level of induced or unrepaired DSBs that best correlates with cell killing


a single DSB is lethal to yeast


enzymatically produced DSBs (produced by inserting DNA restriction enzymes into cells) gives the same pattern of chromosome damage and lethality as radiation


microbeam irradiation has shown the cell nucleus to be the most radiation sensitive site in the cell


the extreme radiosensitivity of some mutant cell lines is due to defects in DSB repair.

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Jan 2, 2017 | Posted by in GENERAL RADIOLOGY | Comments Off on radiation, free radical generation, subcellular radiogenic damage

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