Calculated strand breaks from (125)I in coiled DNA.

Area of Science:

• Radiological Physics
• Molecular Biology
• DNA Damage Mechanisms

Background:

• Iodine-125 ((125)I) decay releases Auger electrons, causing DNA damage.
• Understanding DNA damage from incorporated radionuclides is crucial for radiation biology and dosimetry.
• The influence of DNA structure on damage induction by Auger emitters requires detailed investigation.

Purpose of the Study:

• To calculate DNA single-strand breaks (SSB) and double-strand breaks (DSB) induced by (125)I decay using a B-DNA model.
• To assess the contributions of direct DNA damage and hydroxyl radical (OH) damage.
• To evaluate the effects of DNA higher-order structure on damage induction at different decay sites.

Main Methods:

• Utilized a Monte Carlo track structure code to simulate electron and radical transport through linear and higher-order B-DNA models.
• Tracked electrons, OH, and H radicals originating from (125)I decay.
• Scored direct and indirect DNA hits to quantify SSB and DSB yields.

Main Results:

• Different (125)I decay locations yielded varying DSB numbers (0.83, 0.86, 1.33 per decay).
• Radical attack contributed significantly to DSBs, ranging from 50% to 70% in the entire model.
• Radical damage contribution was higher (up to 67%) at local sites and consistently high (70-80%) at distant locations.

Conclusions:

• DNA coiling (higher-order structure) substantially alters DSB yields and the proportion of radical damage.
• Local DNA damage is more sensitive to higher-order structure than damage at distant sites.
• Radical attack remains the predominant mechanism for DNA damage at locations distant from the (125)I incorporation site.