Calculated strand breaks from ¹²⁵I in coiled DNA

Abstract

Purpose: DNA single strand breaks (SSB) and double-strand breaks (DSB) induced by Auger electrons from incorporated ¹²⁵I 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.

Method: 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 ¹²⁵I decay locations produced different number of DSBs and fraction of radical damage. The average number of DSB per ¹²⁵I 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 ¹²⁵I 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.

Keywords:

• Auger electron
• Monte Carlo
• track structure
• ¹²⁵I
• DNA damage
• direct and indirect damage