Multiple DNA damages induced by water radiolysis demonstrated using a dynamic Monte Carlo code.

Area of Science:

• Radiation chemistry and radiobiology
• Molecular biophysics
• Computational modeling of biological processes

Background:

• Ionizing radiation induces DNA damage through water radiolysis, initiating radiobiological effects.
• The precise characteristics of clustered DNA damage, including critical size and lesion types, remain poorly understood.
• Understanding initial DNA damage is crucial for predicting cellular responses to radiation.

Purpose of the Study:

• To investigate the formation and characteristics of multiple DNA damage sites resulting from water molecule ionization.
• To determine the reaction probabilities and spatial distribution of chemical lesions near DNA.
• To elucidate the potential pathway from initial clustered damage to DNA double-strand breaks (DSBs).

Main Methods:

• Development of a dynamic Monte Carlo code to simulate the chemical processes following ionization.
• Theoretical calculation of reaction probabilities for hydroxyl radicals and hydrated electrons.
• Analysis of lesion spatial distribution as a function of spur radius and DNA proximity.

Main Results:

• A single spur can generate hydroxyl radicals and hydrated electrons capable of reacting within 10 base pairs of DNA.
• This reaction can induce clustered DNA damage, including single-strand breaks and reductive nucleobase damage.
• The probability of this specific clustered damage occurring is low (≤ 0.4%).

Conclusions:

• The study proposes a mechanism for generating complex, clustered DNA damage sites from single ionization events.
• Such clustered damage, if formed, can potentially lead to DNA double-strand breaks (DSBs).
• DSBs are challenging for cells to repair, potentially causing mutations, cell death, or genomic instability.