The cellular environment in computer simulations of radiation-induced damage to DNA |
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Authors: | V V Moiseenko R N Hamm A J Waker W V Prestwich |
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Institution: | (1) Physics Department, London Regional Cancer Centre, 790 Commissioners Road East, London, Ontario N6A 4L6, Canada Tel.: +1-519-6858300, ext. 53281 Fax: +1-519-6858658 e-mail: vmoiseen@phy.lrcc.on.ca, CA;(2) Oak Ridge National Laboratory, Oak Ridge, TN 37831-6123, USA, US;(3) AECL, Chalk River Laboratories, Chalk River, Ontario K0J 1J0, Canada, CA;(4) McMaster University, Department of Physics and Astronomy, Hamilton, Ontario L8S 4K1, Canada, CA |
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Abstract: | 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 a 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 3×109 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.
Received: 3 June 1998 / Accepted in revised form: 16 July 1998 |
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