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DC Field | Value | Language |
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dc.contributor.author | Ulus-Senguloglu, G | - |
dc.contributor.author | Arlett, CF | - |
dc.contributor.author | Plowman, PN | - |
dc.contributor.author | Parnell, J | - |
dc.contributor.author | Patel, N | - |
dc.contributor.author | Bourton, EC | - |
dc.contributor.author | Parris, CN | - |
dc.date.accessioned | 2013-02-11T14:46:19Z | - |
dc.date.available | 2013-02-11T14:46:19Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | British Journal of Cancer, 107(9): 1506 - 1513, Oct 2012 | en_US |
dc.identifier.issn | 0007-0920 | - |
dc.identifier.uri | http://www.nature.com/bjc/journal/v107/n9/full/bjc2012443a.html | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/7233 | - |
dc.description | Copyright @ 2012 Nature Publishing Group | en_US |
dc.description | This article has been made available through the Brunel Open Access Publishing Fund. | - |
dc.description.abstract | Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity. | en_US |
dc.description.sponsorship | This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund. | en_US |
dc.language | eng | - |
dc.language.iso | en | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.subject | Cellular radiosensitivity | en_US |
dc.subject | Defective DNA repair | en_US |
dc.subject | Artemis overexpression | en_US |
dc.title | Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1038/bjc.2012.443 | - |
pubs.organisational-data | /Brunel | - |
pubs.organisational-data | /Brunel/Brunel Active Staff | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care/Biological Sciences | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute for Ageing Studies | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute of Cancer Genetics and Pharmacogenomics | - |
Appears in Collections: | Biological Sciences Publications Community Health and Public Health Brunel OA Publishing Fund Dept of Life Sciences Research Papers |
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Notice.pdf | 91.77 kB | Adobe PDF | View/Open |
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