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...

Full description

Bibliographic Details
Main Authors: Matus Durdik, Eva Markova, Pavol Kosik, Katarina Vigasova, Sachin Gulati, Lukas Jakl, Katarina Vrobelova, Marta Fekete, Ingrid Zavacka, Margita Pobijakova, Zuzana Dolinska, Igor Belyaev
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/4/1122
_version_ 1797606319254929408
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.
first_indexed 2024-03-11T05:13:31Z
format Article
id doaj.art-e6a6a4874f1f42ab8a23cd8c98f847f6
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-03-11T05:13:31Z
publishDate 2023-04-01
publisher MDPI AG
record_format Article
series Biomedicines
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
work_keys_str_mv AT matusdurdik assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT evamarkova assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT pavolkosik assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT katarinavigasova assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT sachingulati assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT lukasjakl assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT katarinavrobelova assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT martafekete assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT ingridzavacka assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT margitapobijakova assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT zuzanadolinska assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers
AT igorbelyaev assessmentofindividualradiosensitivityinbreastcancerpatientsusingacombinationofbiomolecularmarkers