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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, Vol. 99, No. 3, 06.2011, p. 362-6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Chua, MLK, Somaiah, N, A'Hern, R, Davies, S, Gothard, L, Yarnold, J & Rothkamm, K 2011, 'Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy', RADIOTHER ONCOL, vol. 99, no. 3, pp. 362-6. https://doi.org/10.1016/j.radonc.2011.05.071

APA

Chua, M. L. K., Somaiah, N., A'Hern, R., Davies, S., Gothard, L., Yarnold, J., & Rothkamm, K. (2011). Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. RADIOTHER ONCOL, 99(3), 362-6. https://doi.org/10.1016/j.radonc.2011.05.071

Vancouver

Chua MLK, Somaiah N, A'Hern R, Davies S, Gothard L, Yarnold J et al. Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. RADIOTHER ONCOL. 2011 Jun;99(3):362-6. https://doi.org/10.1016/j.radonc.2011.05.071

Bibtex

@article{85488d0707534d4eb69461df86a52ba7,
title = "Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy",
abstract = "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.",
keywords = "Aged, Breast Neoplasms/radiotherapy, Case-Control Studies, Chromosome Aberrations, DNA Breaks, Double-Stranded, Female, Humans, Lymphocytes/metabolism, Microscopy, Fluorescence, Radiation Tolerance/genetics, Randomized Controlled Trials as Topic, Retrospective Studies, Statistics, Nonparametric",
author = "Chua, {Melvin Lee Kiang} and Navita Somaiah and Roger A'Hern and Sue Davies and Lone Gothard and John Yarnold and Kai Rothkamm",
note = "Copyright {\textcopyright} 2011 Elsevier Ireland Ltd. All rights reserved.",
year = "2011",
month = jun,
doi = "10.1016/j.radonc.2011.05.071",
language = "English",
volume = "99",
pages = "362--6",
journal = "RADIOTHER ONCOL",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

RIS

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 -