RESUMO
Objectives: To enhance the efficiency of radiotherapy (RT), implementation of individual-based treatment is essential. In this way, determining individual intrinsic radiosensitivity (IRS) can be useful to achieve minimal adverse effects of RT. The present study aimed to identify IRS of breast cancer (BC) patients through determination of radiation-induced DNA double-strand breaks (DSBs), repair kinetics, and acute normal tissue complications induced by RT. Materials and Methods: DSBs induction and its repair kinetics in 50 BC patients' lymphocytes were analyzed by flow cytometric analysis of H2AX Ser-139 phosphorylation at 30 min, 3 and 24 hr after in vitro irradiation. In vivo skin dosimetry was done by GAFChromic films and acute skin toxicity was scored by radiation oncologists according to the criteria of Radiation Therapy and Oncology Group (RTOG) in all patients with similar prescribed treatment. Results: The average surface dose for patients ranged from 0.92 to 1.9 Gy and correlation analysis showed no significant relationship with weekly acute skin reactions. Formation of γH2AX after 30 min, slope of dose-response curve and repair kinetics of DSBs after 3 and 24 hr (intrinsic radiosensitivity) were significantly correlated with the RTOG scores following irradiation (clinical radiosensitivity) (r=0.48 and P-value<0.0001, r=0.72 and P-value<0.0001, r=0.48 and P-value<0.001, and finally r=0.53 and P-value<0.001, respectively; (using Pearson's correlation test). Conclusion: Flow cytometric analysis of DNA DSBs by γH2AX measurement has the potential to be developed into a clinical predictor for identifying the overreactor patients prior to RT. Our result suggests that the slope-related quantity based on the linear pattern of the dose-response curve has the merit to predict overreactor patients with a sensitivity of 89% and a specificity of 94%.
RESUMO
OBJECTIVES: The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints. MATERIALS AND METHODS: This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose. RESULTS: The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (P<0.0001). MNBN frequency of MRC5 cells which received the most diluted medium from 4 Gy QU-DB irradiated cells reached the maximum level compared to MNBN frequency of cells that received complete medium (P<0.0001). CONCLUSIONS: Our results showed that RIBE levels decreased at doses above 4 Gy; however, RIBE increased when diluted conditioned medium was transferred to bystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.