The cellular environment in computer simulations of radiation-induced damage to DNA

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x109 dm3 mol-1 s-1. Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10-9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (author)