DNA repair inhibitors sensitize cells differently to high and low LET radiation

Abstract The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clon...

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Autores principales:	Kristina Bannik, Balázs Madas, Sabrina Jarke, Andreas Sutter, Gerhard Siemeister, Christoph Schatz, Dominik Mumberg, Sabine Zitzmann-Kolbe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f2aae56817c41d6985e4f6c67f4daba
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spelling	oai:doaj.org-article:9f2aae56817c41d6985e4f6c67f4daba2021-12-05T12:14:00ZDNA repair inhibitors sensitize cells differently to high and low LET radiation10.1038/s41598-021-02719-92045-2322https://doaj.org/article/9f2aae56817c41d6985e4f6c67f4daba2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02719-9https://doaj.org/toc/2045-2322Abstract The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clonogenic survival, the formation of micronuclei and cell cycle distribution were studied after combining of radiation with DDR inhibitors. The inhibitors sensitized different cancer cell lines to radiation. DNA-PKi affected survival rates in combination with α-radiation in selected cell lines. The sensitization enhancement ratios were in the range of 1.6–1.85 in cancer cells. ATMi sensitized H460 cells and significantly increased the micronucleus frequency for both radiation qualities. ATMi in combination with α-radiation reduced survival of HEK293. A significantly elicited cell cycle arrest in G2/M phase after co-treatment of ATMi with α-radiation and X-ray. The most prominent treatment effect was observed in the HEK293 by combining α-radiation and inhibitions. ATMi preferentially sensitized cancer cells and normal HEK293 cells to α-radiation. DNA-PKi and ATMi can sensitize cancer cells to X-ray, but the effectiveness was dependent on cancer cells itself. α-radiation reduced proliferation in primary fibroblast without G2/M arrest.Kristina BannikBalázs MadasSabrina JarkeAndreas SutterGerhard SiemeisterChristoph SchatzDominik MumbergSabine Zitzmann-KolbeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristina Bannik Balázs Madas Sabrina Jarke Andreas Sutter Gerhard Siemeister Christoph Schatz Dominik Mumberg Sabine Zitzmann-Kolbe DNA repair inhibitors sensitize cells differently to high and low LET radiation
description	Abstract The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clonogenic survival, the formation of micronuclei and cell cycle distribution were studied after combining of radiation with DDR inhibitors. The inhibitors sensitized different cancer cell lines to radiation. DNA-PKi affected survival rates in combination with α-radiation in selected cell lines. The sensitization enhancement ratios were in the range of 1.6–1.85 in cancer cells. ATMi sensitized H460 cells and significantly increased the micronucleus frequency for both radiation qualities. ATMi in combination with α-radiation reduced survival of HEK293. A significantly elicited cell cycle arrest in G2/M phase after co-treatment of ATMi with α-radiation and X-ray. The most prominent treatment effect was observed in the HEK293 by combining α-radiation and inhibitions. ATMi preferentially sensitized cancer cells and normal HEK293 cells to α-radiation. DNA-PKi and ATMi can sensitize cancer cells to X-ray, but the effectiveness was dependent on cancer cells itself. α-radiation reduced proliferation in primary fibroblast without G2/M arrest.
format	article
author	Kristina Bannik Balázs Madas Sabrina Jarke Andreas Sutter Gerhard Siemeister Christoph Schatz Dominik Mumberg Sabine Zitzmann-Kolbe
author_facet	Kristina Bannik Balázs Madas Sabrina Jarke Andreas Sutter Gerhard Siemeister Christoph Schatz Dominik Mumberg Sabine Zitzmann-Kolbe
author_sort	Kristina Bannik
title	DNA repair inhibitors sensitize cells differently to high and low LET radiation
title_short	DNA repair inhibitors sensitize cells differently to high and low LET radiation
title_full	DNA repair inhibitors sensitize cells differently to high and low LET radiation
title_fullStr	DNA repair inhibitors sensitize cells differently to high and low LET radiation
title_full_unstemmed	DNA repair inhibitors sensitize cells differently to high and low LET radiation
title_sort	dna repair inhibitors sensitize cells differently to high and low let radiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9f2aae56817c41d6985e4f6c67f4daba
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DNA repair inhibitors sensitize cells differently to high and low LET radiation

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