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.
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 cancerpatients 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 cancerpatients 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.
Authors: Pavel Lobachevsky; Trevor Leong; Patricia Daly; Jai Smith; Nickala Best; Jonathan Tomaszewski; Ella R Thompson; Na Li; Ian G Campbell; Roger F Martin; Olga A Martin Journal: Cancer Lett Date: 2016-09-28 Impact factor: 8.679
Authors: K Rothkamm; C Beinke; H Romm; C Badie; Y Balagurunathan; S Barnard; N Bernard; H Boulay-Greene; M Brengues; A De Amicis; S De Sanctis; R Greither; F Herodin; A Jones; S Kabacik; T Knie; U Kulka; F Lista; P Martigne; A Missel; J Moquet; U Oestreicher; A Peinnequin; T Poyot; U Roessler; H Scherthan; B Terbrueggen; H Thierens; M Valente; A Vral; F Zenhausern; V Meineke; H Braselmann; M Abend Journal: Radiat Res Date: 2013-07-17 Impact factor: 2.841
Authors: Carsten Herskind; Christopher J Talbot; Sarah L Kerns; Marlon R Veldwijk; Barry S Rosenstein; Catharine M L West Journal: Cancer Lett Date: 2016-03-02 Impact factor: 8.679
Authors: Melvin Lee Kiang Chua; Simon Horn; Navita Somaiah; Sue Davies; Lone Gothard; Roger A'Hern; John Yarnold; Kai Rothkamm Journal: Radiat Environ Biophys Date: 2014-03-13 Impact factor: 1.925