Wirkung schwerer Ionen auf strahlenresistente und strahlensensitive Tumorzellen

The reasons for the highly variable sensitivity of different cell types and tissues against ionising radiation are still unknown. The increased radiosensitivity was observed at the level of reproductive cell death as well as chromosome aberrations. The radiation-induced cell killing and the induction of structural chromosome aberrations in tumour cells irradiated with carbon ions of different energies (100 MeV/u, 200 MeV/u, 400 MeV/u and extended Bragg peak) in comparison with 200 kV X-rays has been analysed in detail in this work. Moreover, repair proteins (DNA-PKCS, Ku 70 und Ku 86) involved in the DNA-PK-dependent NHEJ repair have been investigated. Two tumour cell lines (WiDr and MCF-7) displaying quite different radiosensitivities after irradiation with X-rays were selected for the experiments. The large difference between the intrinsic radiosensitivities of these cell lines was observed also after irradiation with carbon ions. The radiation-induced cell death in the a nalysed cells was mostly due to clonogenic cell death since irradiation induced only a small fraction of apoptotic cell death (< 12 %). The RBE with respect to clonogenic cell death increased with increasing LET in both tumour cell lines. The frequencies of unstable and stable chromosome aberrations increased with increasing LET as well. After irradiation with carbon ions, a higher proportion of complex exchanges including simple and multiple insertions, was found. The induction of protein clusters (DNA-PKCS, Ku 70 und Ku 86) after irradiation with X-rays as well as with carbon ions was comparable with cluster induction in normal epithelial cells. This results show, that the analysed tumour cells possess a proficient NHEJ repair and thus imply that the different radiosensitivities of the analysed tumour cells must have other reasons. The distribution of the various aberration types and the dose-effect-relations of the analysed chromosome aberrations point towards a crucial role of the domain topology and the chromatin structure of the chromosomes in the radiation reaction of these cell lines. In summary, cellular intrinsic radiosensitivity appears to result from coactions of multiple factors including not only the repair efficiency, but also the distribution and the character of the initial damage as well as the structure and the geometrical distribution of the chromosome domains.