Salawu, A., Wright, K., Al-Kathiri, A. et al. (3 more authors) (2018) Sister chromatid exchange and genomic instability in soft tissue sarcomas: Potential implications for response to DNA-damaging treatments. Sarcoma, 2018. 3082526. ISSN 1357-714X
Abstract
Sarcomas are rare heterogeneous malignancies of mesenchymal origin characterised by complex karyotypes but no specific abnormalities. Recurrence is common, and metastatic disease carries poor survival despite standard DNA-damaging radiotherapy or chemotherapy. DNA double-strand breaks (DSBs) are either repaired by mechanisms such as homologous recombination (HR) or result in cell death by apoptosis. Endogenous γH2AX formation and SCE formation are early and late events, respectively, and their levels are considered surrogate measures of genomic instability. Combined γH2AX and SCE analysis was used to evaluate endogenous DNA DSB levels (and their subsequent repair) in 9 primary sarcoma cell lines and compared with well-established commercial lines. All the sarcoma cell lines had elevated γH2AX and SCE levels, but there was no correlation between the DNA DSB frequency and subsequent SCE. Typically, radioresistant osteosarcoma cells had relatively low γH2AX frequency but high SCE counts suggestive of efficient DNA repair. Conversely, liposarcoma cells derived from a radiosensitive tumour had high H2AX but relatively lower SCE levels that may imply inefficient DNA DSB repair. To our knowledge, this is the first report that correlates H2AX and SCE levels in primary sarcoma cell lines and may provide insight into potential response to DNA-damaging treatments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Abdulazeez Salawu et al. This is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Jun 2018 13:55 |
Last Modified: | 14 Jun 2018 13:55 |
Published Version: | https://doi.org/10.1155/2018/3082526 |
Status: | Published |
Publisher: | Hindawi Publishing Corporation |
Refereed: | Yes |
Identification Number: | 10.1155/2018/3082526 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131776 |