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Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities
Author(s) -
Carlomagno Francesca,
Burnet Neil G.,
Turesson Ingela,
Nyman Jan,
Peacock John H.,
Dunning Alison M.,
Ponder Bruce A. J.,
Jackson Stephen P.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000315)85:6<845::aid-ijc18>3.0.co;2-c
Subject(s) - dna repair protein xrcc4 , radiosensitivity , dna repair , biology , dna damage , cell culture , fibroblast , ku70 , non homologous end joining , microbiology and biotechnology , dna , cancer research , dna mismatch repair , genetics , radiation therapy , medicine
In order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double‐strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal‐tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non‐irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA‐PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation‐ induced DSB repair. We also analysed the in vitro enzymatic activities, under non‐irradiated conditions, of the DNA‐PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA‐PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro . The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients. Int. J. Cancer 85:845–849, 2000. © 2000 Wiley‐Liss, Inc.