Qualitative and quantitative investigation of the cytogenetic effects of densely ionizing radiation in vitro and in vivo

• Main Author: Hartel, Carola
• Format: Others
• Language: English; en
• Published: 2010
• Online Access: http://tuprints.ulb.tu-darmstadt.de/2179/1/Doktorarbeit-Hartel.pdf; Hartel, Carola <http://tuprints.ulb.tu-darmstadt.de/view/person/Hartel=3ACarola=3A=3A.html> : Qualitative and quantitative investigation of the cytogenetic effects of densely ionizing radiation in vitro and in vivo. Technische Universität, Darmstadt [Ph.D. Thesis], (2010)

The purpose of this work was to compare the cytogenetic effects of densely and sparsely ionizing radiations in vitro and in vivo. To achieve this, chromosomal aberrations in peripheral blood lymphocytes were exposed in vitro to different doses of X-rays and C-ions with different energies; furthermore, lymphocytes were obtained from prostate-cancer patients before, during and after radiotherapy and analyzed using the multiplex fluorescence in situ hybridization (mFISH) technique. These cancer patients were either treated with C-ion boost irradiation in the course of a conventional photon intensity-modulated radiotherapy (IMRT) or solely with IMRT. Blood samples were taken from each patient before, during, at the end of and one year after the therapy. In the in vitro experiments, an increase in the relative biological effectiveness (RBE) for the induction of chromosomal aberrations with increasing linear energy transfer (LET) of the C-ions was observed in the investigated energy range (270 MeV/u C-ions, LET=14 keV/µm; 100 MeV/u C-ions, LET=29 keV/µm; extended Bragg peak of C-ions, LET=60-85 keV/µm). The ratio of complex to simple exchanges, the C-ratio, which is discussed as a biomarker for densely ionizing radiation, was calculated and a LET- and dose-dependent increase was found. Likewise, the complexity of complex chromosome aberrations increased with LET and dose. For prostate-cancer patients, the frequency of chromosomal aberrations found in the peripheral blood lymphocytes increased during the radiotherapy course; but after the C-ion boost, the frequency was lower than in patients treated with comparable doses of IMRT. No significantly increased C-ratio was found in the patients treated with the C-ion boost compared to the patients treated with IMRT. A higher frequency of aberrations was measured in patients who were exposed to an increased target volume. The aberration frequency decreased significantly in two out of 16 patients in the year after therapy. The study shows that the reduced integral dose applied to normal tissue during the C-ion boost is reflected in a lower chromosomal aberration frequency compared to IMRT. While the in vitro experiments showed an enhanced C-ratio for densely ionizing radiation, no increased C-ratio was observed in the patients' samples after C-ion boost therapy. As mFISH allows identification of individual chromosomes involved in aberrations, the distribution of breakpoints among individual chromosomes and the frequencies of pairwise chromosomal exchanges were analyzed in addition.