Please use this identifier to cite or link to this item:
Title: Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis
Authors: Ulus-Senguloglu, G
Arlett, CF
Plowman, PN
Parnell, J
Patel, N
Bourton, EC
Parris, CN
Keywords: Cellular radiosensitivity;Defective DNA repair;Artemis overexpression
Issue Date: 2012
Publisher: Nature Publishing Group
Citation: British Journal of Cancer, 107(9): 1506 - 1513, Oct 2012
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.
Description: Copyright @ 2012 Nature Publishing Group
This article has been made available through the Brunel Open Access Publishing Fund.
ISSN: 0007-0920
Appears in Collections:Biological Sciences
Community Health and Public Health
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
Notice.pdf91.77 kBAdobe PDFView/Open

Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.