Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters.

2.50
Hdl Handle:
http://hdl.handle.net/10541/87916
Title:
Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters.
Authors:
Eastham, Angela M; Marples, B; Kiltie, Anne E; Orton, C J; West, Catharine M L
Abstract:
A study was made of the neutral comet assay as a potential method for measuring normal cell radiosensitivity. Eleven fibroblast strains were studied comprising nine derived from vaginal biopsies from pretreatment cervical cancer patients and two strains from radiosensitive individuals. DNA double strand break (dsbs) dose-response curves for both initial and residual (20-h repair time) damage were obtained over the dose range 0-240 Gy, with slopes varying 3.2 and 8-fold respectively. Clonogenic cell survival parameters were available for all the cell strains following both high- and low-dose rate irradiation. There were no correlations between the dose-response slope of the initial level of DNA dsbs and parameters that mainly describe the initial portion of clonogenic radiation survival curves (SF2, alpha, D). A significant correlation (r = -0.63, P = 0.04) was found between the extent of residual DNA dsbs and clonogenicity for all 11 fibroblast strains. The parameter showing the highest correlation with fibroblast cell killing (D) for the nine normal fibroblasts alone was the ratio of initial/residual DNA dsb dose-response slope (r = 0.80, P = < 0.01). A significant correlation (r = -0.67, P = 0.03) with clonogenic radiosensitivity was also found for all 11 cell strains when using the ratio of initial/residual DNA dsb damage at a single dose of 180 Gy. This study shows that fibroblast radiosensitivity measured using the neutral comet assay correlates with clonogenic radiation survival parameters, and therefore may have potential value in predictive testing of normal tissue radiosensitivity.
Affiliation:
Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Citation:
Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters. 1999, 79 (9-10):1366-71 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Mar-1999
URI:
http://hdl.handle.net/10541/87916
DOI:
10.1038/sj.bjc.6690219
PubMed ID:
10188877
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorEastham, Angela Men
dc.contributor.authorMarples, Ben
dc.contributor.authorKiltie, Anne Een
dc.contributor.authorOrton, C Jen
dc.contributor.authorWest, Catharine M Len
dc.date.accessioned2009-12-14T16:10:35Z-
dc.date.available2009-12-14T16:10:35Z-
dc.date.issued1999-03-
dc.identifier.citationFibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters. 1999, 79 (9-10):1366-71 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid10188877-
dc.identifier.doi10.1038/sj.bjc.6690219-
dc.identifier.urihttp://hdl.handle.net/10541/87916-
dc.description.abstractA study was made of the neutral comet assay as a potential method for measuring normal cell radiosensitivity. Eleven fibroblast strains were studied comprising nine derived from vaginal biopsies from pretreatment cervical cancer patients and two strains from radiosensitive individuals. DNA double strand break (dsbs) dose-response curves for both initial and residual (20-h repair time) damage were obtained over the dose range 0-240 Gy, with slopes varying 3.2 and 8-fold respectively. Clonogenic cell survival parameters were available for all the cell strains following both high- and low-dose rate irradiation. There were no correlations between the dose-response slope of the initial level of DNA dsbs and parameters that mainly describe the initial portion of clonogenic radiation survival curves (SF2, alpha, D). A significant correlation (r = -0.63, P = 0.04) was found between the extent of residual DNA dsbs and clonogenicity for all 11 fibroblast strains. The parameter showing the highest correlation with fibroblast cell killing (D) for the nine normal fibroblasts alone was the ratio of initial/residual DNA dsb dose-response slope (r = 0.80, P = < 0.01). A significant correlation (r = -0.67, P = 0.03) with clonogenic radiosensitivity was also found for all 11 cell strains when using the ratio of initial/residual DNA dsb damage at a single dose of 180 Gy. This study shows that fibroblast radiosensitivity measured using the neutral comet assay correlates with clonogenic radiation survival parameters, and therefore may have potential value in predictive testing of normal tissue radiosensitivity.en
dc.language.isoenen
dc.subject.meshCell Survival-
dc.subject.meshCesium Radioisotopes-
dc.subject.meshDNA-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDose-Response Relationship, Radiation-
dc.subject.meshElectrophoresis, Agar Gel-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshHumans-
dc.subject.meshRadiation Tolerance-
dc.titleFibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
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