Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy
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Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. / Chua, Melvin Lee Kiang; Somaiah, Navita; A'Hern, Roger; Davies, Sue; Gothard, Lone; Yarnold, John; Rothkamm, Kai.
in: RADIOTHER ONCOL, Jahrgang 99, Nr. 3, 06.2011, S. 362-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy
AU - Chua, Melvin Lee Kiang
AU - Somaiah, Navita
AU - A'Hern, Roger
AU - Davies, Sue
AU - Gothard, Lone
AU - Yarnold, John
AU - Rothkamm, Kai
N1 - Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PY - 2011/6
Y1 - 2011/6
N2 - PURPOSE: To test the association of DNA double-strand break (DSB) repair and chromosomal radiosensitivity in ex vivo irradiated blood lymphocytes with late-onset normal tissue responses following breast radiotherapy.METHODS: Breast cancer patients with minimal (controls) or marked late radiotherapy changes (cases) were retrospectively selected. DSB were quantified by γH2AX/53BP1 immunofluorescence microscopy 0.5 and 24 h after exposure of unstimulated blood lymphocytes to 0.5 and 4 Gy X-rays, respectively. Chromosomal aberrations were scored in blood lymphocyte metaphases after 6 Gy X-rays.RESULTS: Despite similar foci levels at 0.5 h in cases (n=7) and controls (n=7), foci levels 24 h after 4 Gy irradiation differed significantly between them (foci per cell were 12.8 in cases versus 10.2 in controls, p=0.004). Increased chromosomal radiosensitivity was also observed in cases (aberrations per cell were 5.84 in cases versus 3.79 in controls, p=0.001) with exchange and deletion type aberrations contributing equally to the difference between cases and controls. Residual foci correlated with formation of deletions (Spearman's R=0.589, p=0.027) but not exchanges (R=0.367, p=0.197) in blood lymphocytes from the same patients.CONCLUSIONS: Higher levels of exchange type aberrations observed among radiosensitive breast cancer patients suggest a role for DSB misrepair, in addition to residual damage, as determinants of late normal tissue damage. Correlation of residual foci levels with deletion type aberration yields in the same cohort confirms their mechanistic linkage.
AB - PURPOSE: To test the association of DNA double-strand break (DSB) repair and chromosomal radiosensitivity in ex vivo irradiated blood lymphocytes with late-onset normal tissue responses following breast radiotherapy.METHODS: Breast cancer patients with minimal (controls) or marked late radiotherapy changes (cases) were retrospectively selected. DSB were quantified by γH2AX/53BP1 immunofluorescence microscopy 0.5 and 24 h after exposure of unstimulated blood lymphocytes to 0.5 and 4 Gy X-rays, respectively. Chromosomal aberrations were scored in blood lymphocyte metaphases after 6 Gy X-rays.RESULTS: Despite similar foci levels at 0.5 h in cases (n=7) and controls (n=7), foci levels 24 h after 4 Gy irradiation differed significantly between them (foci per cell were 12.8 in cases versus 10.2 in controls, p=0.004). Increased chromosomal radiosensitivity was also observed in cases (aberrations per cell were 5.84 in cases versus 3.79 in controls, p=0.001) with exchange and deletion type aberrations contributing equally to the difference between cases and controls. Residual foci correlated with formation of deletions (Spearman's R=0.589, p=0.027) but not exchanges (R=0.367, p=0.197) in blood lymphocytes from the same patients.CONCLUSIONS: Higher levels of exchange type aberrations observed among radiosensitive breast cancer patients suggest a role for DSB misrepair, in addition to residual damage, as determinants of late normal tissue damage. Correlation of residual foci levels with deletion type aberration yields in the same cohort confirms their mechanistic linkage.
KW - Aged
KW - Breast Neoplasms/radiotherapy
KW - Case-Control Studies
KW - Chromosome Aberrations
KW - DNA Breaks, Double-Stranded
KW - Female
KW - Humans
KW - Lymphocytes/metabolism
KW - Microscopy, Fluorescence
KW - Radiation Tolerance/genetics
KW - Randomized Controlled Trials as Topic
KW - Retrospective Studies
KW - Statistics, Nonparametric
U2 - 10.1016/j.radonc.2011.05.071
DO - 10.1016/j.radonc.2011.05.071
M3 - SCORING: Journal article
C2 - 21704405
VL - 99
SP - 362
EP - 366
JO - RADIOTHER ONCOL
JF - RADIOTHER ONCOL
SN - 0167-8140
IS - 3
ER -