Simulation of DNA fragment distributions after irradiation with photons

The Monte Carlo track structure code PAR-TRAC has been further improved by implementing electron scattering cross-sections for liquid water and by exp licitly modelling the interaction of water radicals with DNA. The model of the genome inside a human cell nucleus in its interphase is based on the at omic coordinates of the DNA double helix with an additional volume for the water shell. The DNA helix is wound around histone complexes, and these nuc leosomes are folded into chromatin fibres and further to fibre loops, which are interconnected to build chromosomes with a territorial organisation. S imulations have been performed for the irradiation of human fibroblast cell s with carbon K and aluminium K ultrasoft x-rays, 220 kVp x-rays and Co-60 gamma-rays. The ratio single-strand breaks to double-strand breaks (ssb/dsb ) for both types of ultrasoft x-rays is lower than for gamma-rays by a fact or of 2. The contributions of direct and indirect effects to strand break i nduction are almost independent of photon energy. Strand break patterns fro m indirect effects reflect differences in the susceptibility of the DNA hel ix to OH. attack inside the chromatin fibre. Distributions of small DNA fra gments (<3 kbp) are determined by the chromatin fibre structure irrespectiv e of whether direct or indirect effects are causing the breaks. In the calc ulated fragment size distributions for larger DNA fragments (>30 kbp), a su bstantial deviation from random breakage is found only for carbon K irradia tion, and is attributed to its inhomogeneous dose distribution inside the c ell nucleus. For the other radiation qualities, the results for larger frag ments can be approximated by random breakage distributions calculated for a yield of dsb which is about 10% lower than the average for the whole genom e. The excess of DNA fragments detected experimentally in the 8-300 kbp reg ion after x-ray irradiation is not seen in our simulation results.