Calculated strand breaks from (125)I in coiled DNA.
OBJECTIVE
DNA single strand breaks (SSB) and double-strand breaks (DSB) induced by Auger electrons from incorporated (125)I decay were calculated using a B-DNA model to assess contributions from direct and OH damage and effects of higher-order structure. Three decay sites, linker DNA, nucleosome, and two adjacent nucleosomes, were assessed and compared to experimental data.


METHODS
A Monte Carlo track structure code for electron was used to track electrons, OH and H radicals through linear and a higher-order model of B-DNA. Direct and indirect DNA hits were scored and used to determine SSB and DSB.


RESULTS
The three different (125)I decay locations produced different number of DSBs and fraction of radical damage. The average number of DSB per (125)I decay was 0.83, 0.86 and 1.33, respectively, for the three sites. OH radical attack contributed to or exclusively caused 70%, 57%, and 50%, of the DSBs located in the entire model. When only 10 base pairs on either side of the incorporation site were considered, radical damage contributions were 40%, 25% and 67%, respectively. Locations distant from the site of incorporation, however, consistently yielded 70-80% of the DSB from radical attack.


CONCLUSIONS
Coiling of DNA can greatly change both the absolute number of DSB per incorporated (125)I decay and the relative contributions of radical damage to the local site of decay and, to a lesser extent, the average over all DNA. Higher order structure only slightly affects the number and quality of DNA damage to distant locations, which is mostly from radical attack.
Goorley
Tim
T
Department of Nuclear Engineering, Massachusetts Institute of Technology, USA.
Terrissol
Michel
M
Nikjoo
Hooshang
H
D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D053904:DNA Breaks, Single-Stranded / Q000528:radiation effects*; D004583:Electrons; D017665:Hydroxyl Radical / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D011851:Radioactivity
D007457:Iodine Radioisotopes; D017665:Hydroxyl Radical; D004247:DNA