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Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure

Predicting the risk of second malignant neoplasms is complicated by uncertainties regarding the shape of the dose–response relationship at high doses. Limited understanding of the competitive relationship between cell killing and the accumulation of DNA lesions at high doses, as well as the effects...

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Autores principales: Akuwudike, Pamela, Tartas, Adrianna, López-Riego, Milagrosa, Toma-Dasu, Iuliana, Wojcik, Andrzej, Lundholm, Lovisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655477/
https://www.ncbi.nlm.nih.gov/pubmed/36361653
http://dx.doi.org/10.3390/ijms232112861
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author Akuwudike, Pamela
Tartas, Adrianna
López-Riego, Milagrosa
Toma-Dasu, Iuliana
Wojcik, Andrzej
Lundholm, Lovisa
author_facet Akuwudike, Pamela
Tartas, Adrianna
López-Riego, Milagrosa
Toma-Dasu, Iuliana
Wojcik, Andrzej
Lundholm, Lovisa
author_sort Akuwudike, Pamela
collection PubMed
description Predicting the risk of second malignant neoplasms is complicated by uncertainties regarding the shape of the dose–response relationship at high doses. Limited understanding of the competitive relationship between cell killing and the accumulation of DNA lesions at high doses, as well as the effects of other modulatory factors unique to radiation exposure during radiotherapy, such as dose heterogeneity across normal tissue and dose fractionation, contribute to these uncertainties. The aim of this study was to analyze the impact of fractionated irradiations on two cell systems, focusing on the endpoints relevant for cancer induction. To simulate the heterogeneous dose distribution across normal tissue during radiotherapy, exponentially growing VH10 fibroblasts and AHH-1 lymphoblasts were irradiated with 9 and 12 fractions (VH10) and 10 fractions (AHH-1) at 0.25, 0.5, 1, or 2 Gy per fraction. The effects on cell growth, cell survival, radiosensitivity and the accumulation of residual DNA damage lesions were analyzed as functions of dose per fraction and the total absorbed dose. Residual γH2AX foci and other DNA damage markers (micronuclei, nuclear buds, and giant nuclei) were accumulated at high doses in both cell types, but in a cell type-dependent manner. The competitive relationship between cell killing and the accumulation of carcinogenic DNA damage following multifractional radiation exposure is cell type-specific.
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spelling pubmed-96554772022-11-15 Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure Akuwudike, Pamela Tartas, Adrianna López-Riego, Milagrosa Toma-Dasu, Iuliana Wojcik, Andrzej Lundholm, Lovisa Int J Mol Sci Article Predicting the risk of second malignant neoplasms is complicated by uncertainties regarding the shape of the dose–response relationship at high doses. Limited understanding of the competitive relationship between cell killing and the accumulation of DNA lesions at high doses, as well as the effects of other modulatory factors unique to radiation exposure during radiotherapy, such as dose heterogeneity across normal tissue and dose fractionation, contribute to these uncertainties. The aim of this study was to analyze the impact of fractionated irradiations on two cell systems, focusing on the endpoints relevant for cancer induction. To simulate the heterogeneous dose distribution across normal tissue during radiotherapy, exponentially growing VH10 fibroblasts and AHH-1 lymphoblasts were irradiated with 9 and 12 fractions (VH10) and 10 fractions (AHH-1) at 0.25, 0.5, 1, or 2 Gy per fraction. The effects on cell growth, cell survival, radiosensitivity and the accumulation of residual DNA damage lesions were analyzed as functions of dose per fraction and the total absorbed dose. Residual γH2AX foci and other DNA damage markers (micronuclei, nuclear buds, and giant nuclei) were accumulated at high doses in both cell types, but in a cell type-dependent manner. The competitive relationship between cell killing and the accumulation of carcinogenic DNA damage following multifractional radiation exposure is cell type-specific. MDPI 2022-10-25 /pmc/articles/PMC9655477/ /pubmed/36361653 http://dx.doi.org/10.3390/ijms232112861 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Akuwudike, Pamela
Tartas, Adrianna
López-Riego, Milagrosa
Toma-Dasu, Iuliana
Wojcik, Andrzej
Lundholm, Lovisa
Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title_full Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title_fullStr Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title_full_unstemmed Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title_short Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
title_sort cell type-specific patterns in the accumulation of dna damage following multifractional radiation exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655477/
https://www.ncbi.nlm.nih.gov/pubmed/36361653
http://dx.doi.org/10.3390/ijms232112861
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