Use of Fluorescence in Situ Hybridization to Determine the Relationship between Chromosome Aberrations and Cell Survival in Eight Human Fibroblast Strains

Abstract

A predictive assay of normal tissue radiosensitivity could benefit ‘treatment tailoring’ of radiotherapy for certain categories of tumour. The use of present clonogenic cell survival assays for this purpose would be impractical in routine clinical practice because of the lengthy assay time. Fluorescence in situ hybridization (FISH) using whole chromosome probes on metaphases was investigated as a potential substitute. Eight human fibroblast cell strains with a range of radiosensitivities were tested. For each strain, cell survival curves were determined and correlated with chromosome aberrations detected by FISH performed on metaphase cells collected 52 h after irradiation. A whole chromosome probe for chromosome 4 was used for all cell strains. The results revealed an increase in the percentage of metaphases with aberrant chromosomes (translocations and/or breaks) with increasing radiation dose for all strains. For the more radiosensitive cell strains there were relatively more aberrant metaphases for a given radiation dose when compared with fibroblasts from a normal donor. The relationship between surviving fraction and chromosome aberrations showed some variation between strains, but a linear regression for all data showed a highly statistically significant correlation (r = 0·89, p < 0·0005). These results suggest that an assay of chromosome damage using FISH could substitute for the clonogenic assay to predict the radiation sensitivity of human fibroblasts.