THE CELLULAR ENVIRONMENT IN COMPUTER-SIMULATIONS OF RADIATION-INDUCEDDAMAGE TO DNA

Radiation-induced DNA single- and double-strand breaks were modeled fo r 660 keV photon radiation and scavenger capacity mimicking the cellul ar environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Mon te Carlo generated electron tracks were used to model energy depositio n in matter and to derive initial spatial distributions of species whi ch 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 fo r hydroxyl radical diffusion in a cellular environment were tested: as sumed exponential survival, time-limited modeling and modeling of reac tions between hydroxyl radicals and scavengers in an encounter-control led manner. Although the method based on modeling scavenging in an enc ounter-controlled manner is more precise, it requires substantially mo re computer resources than either the exponential or time-limiting met hod. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x10(9) dm(3) 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 estima tes 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.