This research was devoted to the study of the cytogenetic effects formation regularities in cancer patients with different tumor localizations, depending on the regimen of irradiation with low linear energy transfer to improve the biological support of radiation therapy.
In a comprehensive study the cytogenetic parameters analysis in radiotherapy cancer patients revealed the cytogenetic effects features and showed the dependence of chromosomal damage on such factors as the radiation source and the volume of the irradiated body fraction. In the study, despite the similar trend of increasing levels of cytogenetic damage during radiation therapy, was found a difference in the accumulation of chromosome aberration, which depended on the irradiation source and the tumor localizations. The higher intensity of chromosome aberration growth was observed in the group of oncogynecological patients. The ratio of the total level of chromosomal aberrations in oncogynecological patients, lung cancer patients and head and neck cancer patients was equal in the middle of the course 1 : 0,55 : 0,39 and at the end of the course – 1 : 0,56 : 0,37. At the same time, despite the higher radiation power on the linear accelerator, the obtained data indicate a more pronounced genotoxic effect in the peripheral blood lymphocytes of cancer patients due to gamma therapy. The ratio of the total level of chromosome type aberrations undergone gamma- and megavolt irradiation in the group of oncogynecological patients was 1 : 0,81 in the middle of the course, at the end of the course – 1 : 0,85, and in the group of lung cancer patients was equal 1 : 0,63 and 1 : 0,69, respectively. The expansion degree of the range of cells with chromosome type aberrations was also higher during gamma-therapeutic irradiation of patients.
The cytogenetic status characteristic of cancer patients with different tumor localizations during therapeutic irradiation was supplemented by the analysis of radiation-nonspecific chromosome aberrations and genomic abnormalities. It was shown that, in contrast to oncogynecological patients and head and neck cancer patients, the level of chromatid type aberrations in the group of lung cancer patients increased from the beginning to the end of radiation therapy, mainly due to chromatid fragments. The ratio of the level of the total chromatid type aberrations frequency before treatment in the groups of oncogynecological patients, lung cancer patients and head and neck cancer patients was 1,0 : 1,4 : 0,7, in the middle of the course was 1,0 : 1,7 : 1,0; at the end of the course – 1,0 : 2,2 : 0,8. At the same time, except for the monotonic growing of polyploid cells level in the oncogynecological group during the course of radiation treatment, changes in the level of genomic abnormalities were found to have fluctuating character and did not depend on the source of radiation and tumors localization.
At the early stage of radiotherapy, it was found that the frequency of radiation exposure markers depended on the tumor localizations but the radiation source did not significantly change the overall cytogenetic picture. A significant difference for chromosome type aberrations in oncogynecological patients in comparison with other patient groups was shown. The ratio of chromosome aberrations for groups of oncogynecological patients, lung cancer patients and head and neck cancer patients was 1 : 0,67 : 0,57.
At the experimental point of ex vivo irradiation at 2 Gy dose with 1 : 9 dilution the total chromosome type aberration level was significantly higher than zero control value for both radiation sources. In addition, the per-cell-distribution of dicentrics was over-dispersed.
The data of the ex vivo experiment with the simulation of partial body irradiation were compared with the results of the in vivo study at γ-irradiation with 60Co and megavolt irradiation. The sensitivity of the cytogenetic test was assessed by the possibility of detecting radiation exposure and its locality at early stage of radiotherapy and in an ex vivo experiment with simulation of local irradiation.
The results of the presented work indicate the importance of a comprehensive study of the irradiation effects from different sources in non-target healthy cells, combining ex vivo and in vivo research. This approach and the developed research design make it possible to correctly assess the effects of local fractionated radiation exposure, which is one of the difficult cases of the irradiation scenario and the consequences of which depend on many factors, such as the source and volume of the irradiated body fraction. All this will contribute to the improvement of the system of biological support of cancer patients during radiation treatment.
Key words: chromosome aberrations, gamma-therapy, megavolt radiation therapy on the linear accelerator, oncogynecological patients, lung cancer patients, head and neck cancer patients.
