Spontaneous and radiation-induced genetic instability of peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n ¼ 50) was examined using the single-cell gel electrophoresis (Comet) assay and a modified G2 micronucleus (MN) test. Cells from apparently healthy donors (n ¼ 16) and from cancer patients (n ¼ 9) with an adverse early skin reaction to radiotherapy (RT) served as references. Nonirradiated cells from the three tested groups exhibited similar baseline levels of DNA fragmentation assessed by the Comet assay. Likewise, the Comet analysis of in vitro irradiated (5 Gy) cells did not reveal any significant differences among the three groups with respect to the initial and residual DNA fragmentation, as well as the DNA repair kinetics. The G2 MN test showed that cells from cancer patients with an adverse skin reaction to RT displayed increased frequencies of both spontaneous and radiation-induced MN compared to healthy control or the group of unselected BC patients. Two patients from the latter group developed an increased early skin reaction to RT, which was associated with an increased initial DNA fragmentation in vitro only in one of them. Cells from the other BC patient exhibited a striking slope in the dose -response curve detected by the G2 MN test. We also found that previous RT strongly increased both spontaneous and in vitro radiation-induced MN levels, and to a lesser extent, the radiation-induced DNA damage assessed by the Comet assay. These data suggest that clinical radiation may provoke genetic instability and/or induce persistent DNA damage in normal cells of cancer patients, thus leading to increased levels of MN induction and DNA fragmentation after irradiation in vitro. Therefore, care has to be taken when blood samples collected postradiotherapeutically are used to assess the radiosensitivity of cancer patients.
Nijmegen breakage syndrome (NBS) patients and carriers are predisposed to malignancy and are often treated with X-irradiation. In the present study, the single-cell gel electrophoresis (Comet) assay was used to examine radiation-induced DNA damage and repair in peripheral blood mononuclear cells from NBS patients (n=13) and carriers (n=36) of six unrelated families. Cells from apparently healthy donors (n=10) and from breast cancer patients with normal clinical radiosensitivity (n=10) served as controls. Cells were irradiated with 5 Gy of X-rays and assayed for initial DNA damage and for residual DNA damage after 40 min of repair; the kinetics of DNA repair also was estimated. In addition, the nuclear area of unirradiated cells was extracted from the Comet data. The initial radiation-induced DNA fragmentation indicated that cells from members of two out of six NBS families were significantly more sensitive to X-irradiation than cells from the controls. Cells from four NBS families had longer DNA repair half-time values, while cells from five NBS families had significantly increased residual DNA damage following repair. The mean nuclear area of unirradiated cells processed in the Comet assay was 1.3-fold higher in cells from all NBS families than in the controls (P<0.05). Notably, the Comet assay parameters (initial and residual DNA damage and the repair kinetics) of irradiated NBS cells predicted the carrier status of the majority (86%) of blindly tested individuals. The prediction of NBS status was higher if the nuclear area of unirradiated cells was used as the endpoint. The results of this study suggest that the impaired radiation response of NBS cells should be taken into account if radiotherapy of NBS patients and carriers is required.
The aim of this study was to present the target volume and irradiation technique in the most complex situation where the breast or chest wall and the locoregional lymphatics (mammaria interna lymph nodes, axillary and supraclavicular lymph nodes) have to be irradiated. The study comprised 125 breast cancer patients treated with curative intent after primary surgery in the last two years at our institute. In 62 cases the target volume included the breast or chest wall and the locoregional lymphatics, which were treated using our irradiation technique. The target conformal irradiation technique is a multiple non-opposed beams one isocenter technique developed to protect the heart and lungs. This technique, consisting of several rotation beams modulated with wedge filters and individual lung absorbers as well as additional fixed beams, was used in our study to apply a homogeneous dose of 46 to 56 Gy to the target volume; the irradiation technique was optimized by means of dose-volume histograms. After pre-localization, the patients underwent computerized tomographic scanning, with sections at 1.0 cm intervals. Contouring of target volume and organs at risk was carried out with a MULTIDATA workstation for regions of interest (mammaria interna and/or axillary and/or supraclavicular lymphatics and the breast or chest wall) as well as the organs at risk, such as heart and lung parenchyma. Planning target volume coverage was examined by three-dimensional isodose visualization for all CT axial sections for each patient. To determine the incidence of acute or late side effects on the lung parenchyma, conventional chest x-rays and CT studies were carried out at 1 month, 3 months and 6 months after completion of radiotherapy. Dose-volume histogram analysis revealed that this irradiation technique permits the application of a homogeneous dose to the target volume, conforming to the ICRU norms. The maximum dose applied to the ipsilateral lung parenchyma was less than 50-70% of the prescribed dose in the target volume. For left-located primaries, the highest dose applied to the myocardium is less than 30-50% of the dose in the target volume. Acute side effects, such as radiation pneumonitis, were noted in 8% (5/62) of the treated patients. Late side effects (grade I) in the lung were observed in 6.4% of the patients (4 patients) and occurred only in areas that had received more than 70% of the prescribed dose. We conclude that it is possible to apply a homogeneous dose distribution with a one isocenter multiple beams irradiation technique to the most complex target volume, such as the breast or chest wall and the locoregional lymphatics, with a minimum of side effects guaranteed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.