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

A. M. Eastham, Brian Marples, A. E. Kiltie, C. J. Orton, C. M.L. West

Research output: Contribution to journalArticle

20 Citations (Scopus)

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, α, 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.

Original languageEnglish (US)
Pages (from-to)1366-1371
Number of pages6
JournalBritish Journal of Cancer
Volume79
Issue number9-10
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Double-Stranded DNA Breaks
Radiation Tolerance
DNA Damage
Fibroblasts
Survival
Comet Assay
Radiation
Uterine Cervical Neoplasms
Cell Survival
Biopsy

Keywords

  • Comet assay
  • DNA damage
  • Fibroblasts
  • Intrinsic radiosensitivity
  • Predictive assays

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters. / Eastham, A. M.; Marples, Brian; Kiltie, A. E.; Orton, C. J.; West, C. M.L.

In: British Journal of Cancer, Vol. 79, No. 9-10, 01.01.1999, p. 1366-1371.

Research output: Contribution to journalArticle

Eastham, A. M. ; Marples, Brian ; Kiltie, A. E. ; Orton, C. J. ; West, C. M.L. / Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates with clonogenic survival parameters. In: British Journal of Cancer. 1999 ; Vol. 79, No. 9-10. pp. 1366-1371.
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