USE OF FLUORESCENCE IN-SITU HYBRIDIZATION TO DETERMINE THE RELATIONSHIP BETWEEN CHROMOSOME-ABERRATIONS AND CELL-SURVIVAL IN 8 HUMAN FIBROBLAST STRAINS

A predictive assay of normal tissue radiosensitivity could benefit 'tr eatment tailoring' of radiotherapy for certain categories of tumour. T he use of present clonogenic cell survival assays for this purpose wou ld be impractical in routine clinical practice because of the lengthy assay time. Fluorescence in situ hybridization (FISH) using whole chro mosome probes on metaphases was investigated as a potential substitute . Eight human fibroblast cell strains with a range of radiosensitiviti es 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 chromosom e probe for chromosome 4 was used for all cell strains. The results re vealed an increase in the percentage of metaphases with aberrant chrom osomes (translocations and/or breaks) with increasing radiation dose f or all strains. For the more radiosensitive cell strains there were re latively more aberrant metaphases for a given radiation dose when comp ared with fibroblasts from a normal donor. The relationship between su rviving fraction and chromosome aberrations showed some variation betw een strains, but a linear regression for all data showed a highly stat istically significant correlation (r = 0.89, p < 0.0005). These result s suggest that an assay of chromosome damage using FISH could substitu te for the clonogenic assay to predict the radiation sensitivity of hu man fibroblasts.