Radiation-induced micronuclei in human fibroblasts in relation to clonogenic radiosensitivity

M. C. O'Driscoll, D. Scott, C. J. Orton*, A. E. Kiltie, S. E. Davidson, R. D. Hunter, C. M.L. West

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

As part of our programme for developing predictive tests for normal tissue response to radiotherapy, we have investigated the efficacy of the cytokinesis-block micronucleus (MN) assay as a means of detecting interindividual differences in cellular radiosensitivity. A study was made of nine fibroblast strains established from vaginal biopsies of pretreatment cervical cancer patients and an ataxia telangiectasia (A-T) cell strain. Cells were irradiated in plateau phase, replated and treated with cytochalasin B 24 h later. MN formation was examined 72 h after irradiation as the number of MN in 100 binucleate cells. The method yielded low spontaneous MN yields (< 7 per 100 cells), and mean induced MN frequencies after 3.5 Gy varied between cell strains from 18 to 144 per 100 cells. However, in repeat experiments, considerable intrastrain variability was observed (CV = 32%), with up to twofold differences in MN yields, although this was less than interstrain variability (CV = 62%). An analysis was made of the relationship between MN results and previously obtained clonogenic survival data. There was a significant correlation between MN yields and clonogenic survival. However, when the A-T strain was excluded from the analysis, the correlation lost significance, mainly because of one slow-growing strain which was the most sensitive to cell killing but had almost the lowest MN frequency. With current methodology, the MN assay on human fibroblasts does not appear to have a role in predictive testing of normal tissue radiosensitivity.

Original languageEnglish
Pages (from-to)1559-1563
Number of pages5
JournalBritish Journal of Cancer
Volume78
Issue number12
DOIs
Publication statusPublished - 1998

Bibliographical note

Funding Information:
Discussions with Professor Jolyon Hendry are gratefully acknowl- edged. This work was supported by the Cancer Research Campaign and the Christie Hospital Endowment Fund.

Keywords

  • Intrinsic radiosensitivity
  • Micronucleus assay
  • Predictive assays
  • Radiotherapy
  • SF2

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