Modelling DNA damage induced by different energy photons and tritium beta-particles

Abstract

The developed model makes predictions compatible with features of available experimental data. Break complexity has to be addressed in biophysical modelling when the relative effectiveness of radiations in DNA damage is studied. Obtained data strongly argue against the dominance of direct radiation action in DNA damage in the cellular environment predicted by some theoretical studies.

Strand Breaks Produced in X-Irradiated Crystalline DNA: Influence of Base Sequence

“…Both of these direct-type lesions could play an important role in the formation of multiply damaged sites (MDS) (21,22), and the neglect of this type of damage in calculations could cause significant under-estimation of the local severity of helical damage. For example, a direct-type strand break situated within 10 bases of an indirect-type strand break could result in a biologically more damaging double strand break (23) (24). In these types of calculations, it is important, therefore, to include the yields and distribution of direct-type damage.…”

Calculation of radiation-induced DNA damage from photons and tritium beta-particles

“…From these two papers, including data summarised by Krisch et al [13], the following values have been set for the model predictions obtained for 137 Cs or x-rays to conform to: an SSB/DSB ratio in nucleosomal DNA of between 20 and 30, DSB yield of 0.5-1×10 -8 Gy -1 bp -1 , an increase of DSB yield by a factor of the order of 2 following removal of the histone core and approximately two-thirds of the produced DSB being hydroxyl radical-mediated. A DSB yield of 1×10 -8 Gy -1 bp -1 is above the values observed in most studies with cellular DNA, which indicate a yield within the range 0.4-0.7×10 -8 Gy -1 bp -1 (see review in [2]). However, although our model does include DNA protection by a nucleosome core, we did not consider a chromatin fibre structure, which might further reduce the break yield [11].…”

“…The method of modelling energy deposition has been described in detail previously [2]. In brief, to model effects from photons, we considered a spherical target with a diameter 1 µm in a photon radiation field.…”

“…Modelling of DNA damage was carried out on a track-by-track basis, i.e. no intertrack interaction was considered [2]. Following modelling of energy deposition in a given target, the projection of this 1 µm spherical target was scanned with a regular grid in x-y directions with a step 2.3 nm for prospective axes of the "beads on the string" sequences.…”

“…We have recently reported [2,3] a model developed to calculate DNA break yields. A Monte Carlo method was applied throughout all the stages involved, from energy deposition to diffusion and reactions between species and DNA.…”