Abstract
BackgroundAs there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. Thus far, the radiobiological effects of these neutrons and a comparison with photons on normal breast cells have not been sufficiently characterised.MethodsMCF10A cells were irradiated with doses of up to 2 Gy with neutrons of different energy spectra and X-rays for comparison. The biological effects of neutrons with a broad energy distribution (<En > = 5.8 MeV), monoenergetic neutrons (1.2 MeV, 0.56 MeV) and of the mixed field of gamma’s and secondary neutrons (<En > = 70.5 MeV) produced by 190 MeV protons impinging on a water phantom, were analysed. The clonogenic survival and the DNA repair capacity were determined and values of relative biological effectiveness were compared. Furthermore, the influence of radiation on the sphere formation was observed to examine the radiation response of the potential fraction of stem like cells within the MCF10A cell population.ResultsX-rays and neutrons caused dose-dependent decreases of survival fractions after irradiations with up to 2 Gy. Monoenergetic neutrons with an energy of 0.56 MeV had a higher effectiveness on the survival fraction with respect to neutrons with higher energies and to the mixed gamma - secondary neutron field induced by proton interactions in water. Similar effects were observed for the DNA repair capacity after exposure to ionising radiation (IR). Both experimental endpoints provided comparable values of the relative biological effectiveness. Significant changes in the sphere formation were notable following the various radiation qualities.ConclusionThe present study compared the radiation response of MCF10A cells after IR with neutrons and photons. For the first time it was shown that monoenergetic neutrons with energies around 1 MeV have stronger radiobiological effects on normal human breast cells with respect to X rays, to neutrons with a broad energy distribution (<En > = 5.8 MeV), and to the mixed gamma - secondary neutron field given by interactions of 190 MeV protons in water. The results of the present study are highly relevant for further investigations of radiation-induced carcinogenesis and are very important in perspective for a better risk assessment after secondary neutron exposure in the field of conventional and proton radiotherapy.
Highlights
As there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus
For DNA damage, represented by Phosphorylated histone 2AX (γH2AX) foci (DSBs) 24 h after radiation exposure, our findings reveal a 2-fold higher response of cells irradiated with high dose rate (HDR) in contrast to low dose rate (LDR) X-rays
Our results demonstrated that the number of residual γH2AX foci 24 h after ionising radiation (IR), as an indicator for Double strand break (DSB), increased as a function of increasing dose, which has been reported by Okumura and colleagues [34], who observed 53BP1 foci as an indicator for DSBs for several time points
Summary
As there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. The incidence of carcinogenesis as a late effect of radiotherapy is discussed in several studies as there is a growing number of long-term cancer survivors [1,2,3,4,5]. The risk for the development of secondary malignant neoplasms is significantly increased, especially for breast cancers among women who were irradiated as a treatment for Hodgkin disease in childhood or adolescence using particle proton therapy [6,7,8,9], which allows a better dose conformation to the target volume than conventional radiotherapy. In order to generate a field of secondary neutrons, similar to that produced during proton therapy, a 190 MeV proton beam was directed onto a water phantom
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