Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions

In cells exposed to low linear energy transfer (LET) ionizing-radiation (IR), double-strand-breaks (DSBs) form within clustered-damage-sites (CDSs) from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that all DSBs form promptly and are immediately detected by the cellula...

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Main Authors:	Singh, Satyendra K, Bencsik-Theilen, Alena, Mladenov, Emil, Jakob, Burkhard, Taucher-Scholz, Gisela, Iliakis, George
Format:	Online
Language:	English
Published:	BioMed Central 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627621/

id	pubmed-3627621
recordtype	oai_dc
spelling	pubmed-36276212013-04-18 Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions Singh, Satyendra K Bencsik-Theilen, Alena Mladenov, Emil Jakob, Burkhard Taucher-Scholz, Gisela Iliakis, George Research In cells exposed to low linear energy transfer (LET) ionizing-radiation (IR), double-strand-breaks (DSBs) form within clustered-damage-sites (CDSs) from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that all DSBs form promptly and are immediately detected by the cellular DNA-damage-response (DDR) apparatus. However, there is evidence that the pool of DSBs detected by physical methods, such as pulsed-field gel electrophoresis (PFGE), comprises not only promptly forming DSBs (prDSBs) but also DSBs developing during lysis at high temperatures from thermally-labile sugar-lesions (TLSLs). We recently demonstrated that conversion of TLSLs to DNA breaks and ultimately to DSBs also occurs in cells during the first hour of post-irradiation incubation at physiological temperatures. Thus, TLSL-dependent DSBs (tlDSBs) are not an avoidable technique-related artifact, but a reality the cell always faces. The biological consequences of tlDSBs and the dependence of their formation on LET require in-depth investigation. Heavy-ions (HI) are a promising high-LET radiation modality used in cancer treatment. HI are also encountered in space and generate serious radiation protection problems to prolonged space missions. Here, we study, therefore, the effect of HI on the yields of tlDSBs and prDSBs. We report a reduction in the yield of tlDBSs stronger than that earlier reported for neutrons, and with pronounced cell line dependence. We conclude that with increasing LET the complexity of CDSs increases resulting in a commensurate increase in the yield prDSBs and a decrease in tlDSBs. The consequences of these effects to the relative biological effectiveness are discussed. BioMed Central 2013-04-02 /pmc/articles/PMC3627621/ /pubmed/23547740 http://dx.doi.org/10.1186/1748-717X-8-77 Text en Copyright © 2013 Singh et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Singh, Satyendra K Bencsik-Theilen, Alena Mladenov, Emil Jakob, Burkhard Taucher-Scholz, Gisela Iliakis, George
spellingShingle	Singh, Satyendra K Bencsik-Theilen, Alena Mladenov, Emil Jakob, Burkhard Taucher-Scholz, Gisela Iliakis, George Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
author_facet	Singh, Satyendra K Bencsik-Theilen, Alena Mladenov, Emil Jakob, Burkhard Taucher-Scholz, Gisela Iliakis, George
author_sort	Singh, Satyendra K
title	Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
title_short	Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
title_full	Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
title_fullStr	Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
title_full_unstemmed	Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions
title_sort	reduced contribution of thermally labile sugar lesions to dna double strand break formation after exposure to heavy ions
description	In cells exposed to low linear energy transfer (LET) ionizing-radiation (IR), double-strand-breaks (DSBs) form within clustered-damage-sites (CDSs) from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that all DSBs form promptly and are immediately detected by the cellular DNA-damage-response (DDR) apparatus. However, there is evidence that the pool of DSBs detected by physical methods, such as pulsed-field gel electrophoresis (PFGE), comprises not only promptly forming DSBs (prDSBs) but also DSBs developing during lysis at high temperatures from thermally-labile sugar-lesions (TLSLs). We recently demonstrated that conversion of TLSLs to DNA breaks and ultimately to DSBs also occurs in cells during the first hour of post-irradiation incubation at physiological temperatures. Thus, TLSL-dependent DSBs (tlDSBs) are not an avoidable technique-related artifact, but a reality the cell always faces. The biological consequences of tlDSBs and the dependence of their formation on LET require in-depth investigation. Heavy-ions (HI) are a promising high-LET radiation modality used in cancer treatment. HI are also encountered in space and generate serious radiation protection problems to prolonged space missions. Here, we study, therefore, the effect of HI on the yields of tlDSBs and prDSBs. We report a reduction in the yield of tlDBSs stronger than that earlier reported for neutrons, and with pronounced cell line dependence. We conclude that with increasing LET the complexity of CDSs increases resulting in a commensurate increase in the yield prDSBs and a decrease in tlDSBs. The consequences of these effects to the relative biological effectiveness are discussed.
publisher	BioMed Central
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627621/
_version_	1611970419316752384

Reduced contribution of thermally labile sugar lesions to DNA double strand break formation after exposure to heavy ions

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