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A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks
Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chroma...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527830/ https://www.ncbi.nlm.nih.gov/pubmed/18665175 http://dx.doi.org/10.1038/sj.bjc.6604514 |
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author | Terry, S Y A Riches, A C Bryant, P E |
author_facet | Terry, S Y A Riches, A C Bryant, P E |
author_sort | Terry, S Y A |
collection | PubMed |
description | Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chromatid breaks (or chromatid ‘radiosensitivity’) in irradiated T-lymphocytes from different normal individuals and cancer cases are as yet unclear. Here we report evidence that topoisomerase IIα expression level is a factor determining chromatid radiosensitivity. We have exposed the promyelocytic leukaemic cell line (HL60) and two derived variant cell lines (MX1 and MX2) that have acquired resistance to mitoxantrone and low expression of topoisomerase II α, to low doses of γ-radiation and scored the induced chromatid breaks. Chromatid break frequencies were found to be significantly lower in the variant cell lines, compared with their parental HL60 cell line. Rejoining of DSB in the variant cell lines was similar to that in the parental HL60 strain. Our results indicate the indirect involvement of topoisomerase IIα in the formation of radiation-induced chromatid breaks from DSB, and suggest topoisomerase IIα as a possible factor in the inter-individual variation in chromatid radiosensitivity. |
format | Text |
id | pubmed-2527830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-25278302009-09-11 A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks Terry, S Y A Riches, A C Bryant, P E Br J Cancer Genetics and Genomics Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chromatid breaks (or chromatid ‘radiosensitivity’) in irradiated T-lymphocytes from different normal individuals and cancer cases are as yet unclear. Here we report evidence that topoisomerase IIα expression level is a factor determining chromatid radiosensitivity. We have exposed the promyelocytic leukaemic cell line (HL60) and two derived variant cell lines (MX1 and MX2) that have acquired resistance to mitoxantrone and low expression of topoisomerase II α, to low doses of γ-radiation and scored the induced chromatid breaks. Chromatid break frequencies were found to be significantly lower in the variant cell lines, compared with their parental HL60 cell line. Rejoining of DSB in the variant cell lines was similar to that in the parental HL60 strain. Our results indicate the indirect involvement of topoisomerase IIα in the formation of radiation-induced chromatid breaks from DSB, and suggest topoisomerase IIα as a possible factor in the inter-individual variation in chromatid radiosensitivity. Nature Publishing Group 2008-08-19 2008-07-29 /pmc/articles/PMC2527830/ /pubmed/18665175 http://dx.doi.org/10.1038/sj.bjc.6604514 Text en Copyright © 2008 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Genetics and Genomics Terry, S Y A Riches, A C Bryant, P E A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title | A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title_full | A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title_fullStr | A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title_full_unstemmed | A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title_short | A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks |
title_sort | role for topoisomerase iiα in the formation of radiation-induced chromatid breaks |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527830/ https://www.ncbi.nlm.nih.gov/pubmed/18665175 http://dx.doi.org/10.1038/sj.bjc.6604514 |
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