A correlation between residual DNA double-strand breaks and clonogenic measurements of radiosensitivity in fibroblasts from preradiotherapy cervix cancer patients.

2.50
Hdl Handle:
http://hdl.handle.net/10541/94920
Title:
A correlation between residual DNA double-strand breaks and clonogenic measurements of radiosensitivity in fibroblasts from preradiotherapy cervix cancer patients.
Authors:
Kiltie, Anne E; Orton, C Jane; Ryan, Anderson J; Roberts, Stephen A; Marples, Brian; Davidson, Susan E; Hunter, Robin D; Margison, Geoffrey P; West, Catharine M L; Hendry, Jolyon H
Abstract:
PURPOSE: To study the relationship between residual DNA damage and clonogenic measurements of radiosensitivity in fibroblasts from pretreatment cervix cancer patients. METHODS AND MATERIALS: Early passage vaginal fibroblasts from nine preradiotherapy cervix cancer patients and two radiosensitive skin fibroblast cell strains were studied. Cell survival was measured by clonogenic assay following both high and low dose rate irradiation. Residual DNA damage was measured using pulsed-field gel electrophoresis (PFGE) after irradiating radiolabeled, plateau-phase cells at 37 degrees C and allowing 24 h for repair. DNA damage was expressed both in terms of the residual damage slope (fitted to data from 60 to 150 Gy) and the fraction of activity released (FAR) following 150 Gy. RESULTS: The surviving fraction at 2 Gy (SF2) values after high dose rate irradiation for the vaginal fibroblasts ranged from 0.15 to 0.32 (a 2.2-fold difference). When the two radiosensitive cell strains were included, residual damage, expressed as the residual damage slope, correlated with alpha (r = 0.82, p = 0.002), D bar (r = -0.91, p < 0.001) and SF2 (p = -0.79, p = 0.004), and when the vaginal fibroblasts alone were studied, the residual damage slope again correlated with clonogenic survival, although less strongly [alpha (r = 0.66, p = 0.053), D bar (r = -0.83, p = 0.006), and SF2 (r = -0.63, p = 0.07)]. Within the group of vaginal fibroblasts there was a 4.0-fold difference in residual DNA damage slope. When residual damage was expressed as FAR at 150 Gy, then for all cell strains the correlations were alpha: r = 0.78, p = 0.004, D bar: r = -0.86, p = 0.001, and SF2: r = -0.78, p = 0.004, and for the vaginal fibroblast strains alone the correlations were alpha: r = 0.60, p = 0.088, D bar: r = -0.75, p = 0.02, and SF2: r = 0.62, p = 0.077. CONCLUSION: This study confirms previous findings that residual DNA damage correlates with clonogenic survival in fibroblasts. In addition, it demonstrates a correlation for fibroblasts from pretreatment cervix cancer patients demonstrating a relatively small range of SF2 values.
Affiliation:
Department of Experimental Radiation Oncology, Christie Hospital NHS Trust, Manchester, UK.
Citation:
A correlation between residual DNA double-strand breaks and clonogenic measurements of radiosensitivity in fibroblasts from preradiotherapy cervix cancer patients. 1997, 39 (5):1137-44 Int. J. Radiat. Oncol. Biol. Phys.
Journal:
International Journal of Radiation Oncology, Biology, Physics
Issue Date:
1-Dec-1997
URI:
http://hdl.handle.net/10541/94920
DOI:
10.1016/S0360-3016(97)00545-2
PubMed ID:
9392556
Type:
Article
Language:
en
ISSN:
0360-3016
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKiltie, Anne Een
dc.contributor.authorOrton, C Janeen
dc.contributor.authorRyan, Anderson Jen
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorMarples, Brianen
dc.contributor.authorDavidson, Susan Een
dc.contributor.authorHunter, Robin Den
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorWest, Catharine M Len
dc.contributor.authorHendry, Jolyon Hen
dc.date.accessioned2010-03-24T14:48:22Z-
dc.date.available2010-03-24T14:48:22Z-
dc.date.issued1997-12-01-
dc.identifier.citationA correlation between residual DNA double-strand breaks and clonogenic measurements of radiosensitivity in fibroblasts from preradiotherapy cervix cancer patients. 1997, 39 (5):1137-44 Int. J. Radiat. Oncol. Biol. Phys.en
dc.identifier.issn0360-3016-
dc.identifier.pmid9392556-
dc.identifier.doi10.1016/S0360-3016(97)00545-2-
dc.identifier.urihttp://hdl.handle.net/10541/94920-
dc.description.abstractPURPOSE: To study the relationship between residual DNA damage and clonogenic measurements of radiosensitivity in fibroblasts from pretreatment cervix cancer patients. METHODS AND MATERIALS: Early passage vaginal fibroblasts from nine preradiotherapy cervix cancer patients and two radiosensitive skin fibroblast cell strains were studied. Cell survival was measured by clonogenic assay following both high and low dose rate irradiation. Residual DNA damage was measured using pulsed-field gel electrophoresis (PFGE) after irradiating radiolabeled, plateau-phase cells at 37 degrees C and allowing 24 h for repair. DNA damage was expressed both in terms of the residual damage slope (fitted to data from 60 to 150 Gy) and the fraction of activity released (FAR) following 150 Gy. RESULTS: The surviving fraction at 2 Gy (SF2) values after high dose rate irradiation for the vaginal fibroblasts ranged from 0.15 to 0.32 (a 2.2-fold difference). When the two radiosensitive cell strains were included, residual damage, expressed as the residual damage slope, correlated with alpha (r = 0.82, p = 0.002), D bar (r = -0.91, p < 0.001) and SF2 (p = -0.79, p = 0.004), and when the vaginal fibroblasts alone were studied, the residual damage slope again correlated with clonogenic survival, although less strongly [alpha (r = 0.66, p = 0.053), D bar (r = -0.83, p = 0.006), and SF2 (r = -0.63, p = 0.07)]. Within the group of vaginal fibroblasts there was a 4.0-fold difference in residual DNA damage slope. When residual damage was expressed as FAR at 150 Gy, then for all cell strains the correlations were alpha: r = 0.78, p = 0.004, D bar: r = -0.86, p = 0.001, and SF2: r = -0.78, p = 0.004, and for the vaginal fibroblast strains alone the correlations were alpha: r = 0.60, p = 0.088, D bar: r = -0.75, p = 0.02, and SF2: r = 0.62, p = 0.077. CONCLUSION: This study confirms previous findings that residual DNA damage correlates with clonogenic survival in fibroblasts. In addition, it demonstrates a correlation for fibroblasts from pretreatment cervix cancer patients demonstrating a relatively small range of SF2 values.en
dc.language.isoenen
dc.subjectCancer DNAen
dc.subjectUterine Cervical Canceren
dc.subject.meshCell Survival-
dc.subject.meshDNA Damage-
dc.subject.meshDNA, Neoplasm-
dc.subject.meshDose-Response Relationship, Radiation-
dc.subject.meshElectrophoresis, Gel, Pulsed-Field-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshHumans-
dc.subject.meshRadiation Tolerance-
dc.subject.meshRadiotherapy Dosage-
dc.subject.meshReproducibility of Results-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleA correlation between residual DNA double-strand breaks and clonogenic measurements of radiosensitivity in fibroblasts from preradiotherapy cervix cancer patients.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Radiation Oncology, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalInternational Journal of Radiation Oncology, Biology, Physicsen

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