Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers
About 5% of patients undergoing radiotherapy (RT) develop RT-related side effects. To assess individual radiosensitivity, we collected peripheral blood from breast cancer patients before, during and after the RT, and γH2AX/53BP1 foci, apoptosis, chromosomal aberrations (CAs) and micronuclei (MN) wer...
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MDPI AG
2023-04-01
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author | Matus Durdik Eva Markova Pavol Kosik Katarina Vigasova Sachin Gulati Lukas Jakl Katarina Vrobelova Marta Fekete Ingrid Zavacka Margita Pobijakova Zuzana Dolinska Igor Belyaev |
author_facet | Matus Durdik Eva Markova Pavol Kosik Katarina Vigasova Sachin Gulati Lukas Jakl Katarina Vrobelova Marta Fekete Ingrid Zavacka Margita Pobijakova Zuzana Dolinska Igor Belyaev |
author_sort | Matus Durdik |
collection | DOAJ |
description | About 5% of patients undergoing radiotherapy (RT) develop RT-related side effects. To assess individual radiosensitivity, we collected peripheral blood from breast cancer patients before, during and after the RT, and γH2AX/53BP1 foci, apoptosis, chromosomal aberrations (CAs) and micronuclei (MN) were analyzed and correlated with the healthy tissue side effects assessed by the RTOG/EORTC criteria. The results showed a significantly higher level of γH2AX/53BP1 foci before the RT in radiosensitive (RS) patients in comparison to normal responding patients (NOR). Analysis of apoptosis did not reveal any correlation with side effects. CA and MN assays displayed an increase in genomic instability during and after RT and a higher frequency of MN in the lymphocytes of RS patients. We also studied time kinetics of γH2AX/53BP1 foci and apoptosis after in vitro irradiation of lymphocytes. Higher levels of primary 53BP1 and co-localizing γH2AX/53BP1 foci were detected in cells from RS patients as compared to NOR patients, while no difference in the residual foci or apoptotic response was found. The data suggested impaired DNA damage response in cells from RS patients. We suggest γH2AX/53BP1 foci and MN as potential biomarkers of individual radiosensitivity, but they need to be evaluated with a larger cohort of patients for clinics. |
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spelling | doaj.art-e6a6a4874f1f42ab8a23cd8c98f847f62023-11-17T18:26:50ZengMDPI AGBiomedicines2227-90592023-04-01114112210.3390/biomedicines11041122Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular MarkersMatus Durdik0Eva Markova1Pavol Kosik2Katarina Vigasova3Sachin Gulati4Lukas Jakl5Katarina Vrobelova6Marta Fekete7Ingrid Zavacka8Margita Pobijakova9Zuzana Dolinska10Igor Belyaev11Department of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDepartment of Radiation Oncology, Radiological Centrum, National Cancer Institute, 812 50 Bratislava, SlovakiaDepartment of Radiation Oncology, Radiological Centrum, National Cancer Institute, 812 50 Bratislava, SlovakiaDepartment of Radiation Oncology, Radiological Centrum, National Cancer Institute, 812 50 Bratislava, SlovakiaDepartment of Radiation Oncology, Radiological Centrum, National Cancer Institute, 812 50 Bratislava, SlovakiaDepartment of Radiobiology, Cancer Research Institute, Biomedical Research Center v.v.i., Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaAbout 5% of patients undergoing radiotherapy (RT) develop RT-related side effects. To assess individual radiosensitivity, we collected peripheral blood from breast cancer patients before, during and after the RT, and γH2AX/53BP1 foci, apoptosis, chromosomal aberrations (CAs) and micronuclei (MN) were analyzed and correlated with the healthy tissue side effects assessed by the RTOG/EORTC criteria. The results showed a significantly higher level of γH2AX/53BP1 foci before the RT in radiosensitive (RS) patients in comparison to normal responding patients (NOR). Analysis of apoptosis did not reveal any correlation with side effects. CA and MN assays displayed an increase in genomic instability during and after RT and a higher frequency of MN in the lymphocytes of RS patients. We also studied time kinetics of γH2AX/53BP1 foci and apoptosis after in vitro irradiation of lymphocytes. Higher levels of primary 53BP1 and co-localizing γH2AX/53BP1 foci were detected in cells from RS patients as compared to NOR patients, while no difference in the residual foci or apoptotic response was found. The data suggested impaired DNA damage response in cells from RS patients. We suggest γH2AX/53BP1 foci and MN as potential biomarkers of individual radiosensitivity, but they need to be evaluated with a larger cohort of patients for clinics.https://www.mdpi.com/2227-9059/11/4/1122breast cancerDNA repair γH2AX/53BP1 fociapoptosisMetaferhuman lymphocytesradiotherapy |
spellingShingle | Matus Durdik Eva Markova Pavol Kosik Katarina Vigasova Sachin Gulati Lukas Jakl Katarina Vrobelova Marta Fekete Ingrid Zavacka Margita Pobijakova Zuzana Dolinska Igor Belyaev Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers Biomedicines breast cancer DNA repair γH2AX/53BP1 foci apoptosis Metafer human lymphocytes radiotherapy |
title | Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers |
title_full | Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers |
title_fullStr | Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers |
title_full_unstemmed | Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers |
title_short | Assessment of Individual Radiosensitivity in Breast Cancer Patients Using a Combination of Biomolecular Markers |
title_sort | assessment of individual radiosensitivity in breast cancer patients using a combination of biomolecular markers |
topic | breast cancer DNA repair γH2AX/53BP1 foci apoptosis Metafer human lymphocytes radiotherapy |
url | https://www.mdpi.com/2227-9059/11/4/1122 |
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