Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100–200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments.

Effects on the heart constitute a potentially significant and serious clinical problem in primary radiation therapy of early breast cancer. Increased cardiac mortality among irradiated patients may offset the potential benefit in terms of a reduced risk of recurrence or of death from breast cancer. Clinical data on long-term cardiac mortality among breast cancer patients included in two randomized trials (the Stockholm and Oslo studies) of radiation therapy as an adjunct to primary surgery were analysed using the relative seriality model of radiation response. Five different radiation therapy techniques were used in the trials. The original treatment plans were recalculated on a group of model patients using a three-dimensional treatment planning system. A mean dose-volume histogram (DVH) was calculated for each treatment technique. Both heart and myocardium, i.e. excluding circulating blood within the heart, were separately investigated as risk organs. Model parameters, (D50, i.e. the dose giving 50% complication probability; gamma, i.e. the maximum relative slope of the dose-response curve; s, describing the organ relative seriality) were determined by a chi 2 fitting of the calculated probability of excess cardiac mortality, based on the DVHs, to the incidence data. Computed complication probabilities for each treatment technique were modelled within the 95% confidence interval (CI) of the clinical incidence data. It was shown that the relative seriality model, assuming a homogeneous radiation sensitivity within the volume of the heart/myocardium can be used to describe the incidence data. A small dependence on the volume was found. The results do not, however, exclude the possibility that more sensitive structures within the myocardium are the main target for radiation.

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Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX) phosphorylation (γ-H2AX), a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours) and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.