Computational approach for determining the spectrum of DNA damage induced by ionizing radiation

To study the characteristics of molecular damage induced by ionizing radiat ion at the DNA level, Monte Carlo track simulation of energetic electrons a nd ions in liquid water, a canonical model of B-DNA, and a comprehensive cl assification of DNA damage in terms of the origin and complexity of damage were used to calculate the frequencies of simple and complex strand breaks. A threshold energy of 17.5 eV was used to model the damage by direct energ y deposition, and a probability of 0.13 was applied to model the induction of a single-strand break produced in DNA by OH radical reactions. For preli minary estimates, base damage was assumed to be induced by the same direct energy threshold deposition or by the reaction of an OH radical with the ba se, with a probability of 0.8. Computational data are given on the complexi ty of damage, including base damage by electrons with energies of 100-4500 eV and ions with energies of 0.3-4.0 MeV/nucleon (59-9 keV mum(-1) protons and 170-55 keV mum(-1) alpha particles). Computational data are presented o n the frequencies of single- and double-strand breaks induced as a function of the LET of the particles, and on the relative frequencies of complex si ngle- and double-strand breaks for electrons. The modeling and calculations of strand breaks show that: (1) The yield of strand breaks per unit absorb ed dose is nearly constant over a wide range of LET. (2) The majority of DN A damage is of a simple type, but the majority of the simple single-strand breaks are accompanied by at least one base damage. (3) For low-energy elec trons, nearly 20-30% of the double-strand breaks are of a complex type by v irtue of additional breaks. The proportion of this locally clustered damage increases with LET, reaching about 70% for the highest-LET a particles mod eled, with the complexity of damage increasing further, to about 90%,,when base damage is considered. (4) The extent of damage in the local hit region of the DNA duplex is mostly limited to a length of a few base pairs. (5) T he frequency of base damage when no strand breaks are present in the hit se gment of DNA varies between 20-40% as a function of LET for protons and a p articles. (C) 2001 by Radiation Research Society.