Prediction of human cell radiosensitivity: Comparison of clonogenic assay with chromosome aberrations scored using premature chromosome condensation with fluorescence in situ hybridization

Abstract

Purpose : The purpose of the present investigation was to determine whether chromosome aberrations scored by premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) can predict the radio sensitivity of human cell lines, thereby providing a possible means of assessing the in situ radiosensitivity of normal tissues and the radiocurability of individual human cancers. Methods and Materials : We used four cells lines of different radiosensitivity: normal human fibroblasts (AG1522), ataxia-telangiectasia fibroblasts (AT2052), a human fibrosarcoma cell line (HT1080), and a human melanoma cell line (melanoma 903). These were irradiated in plateau phase with a range of doses and assessed both for clonogenic cell survival and for aberrations in a single chromosome (number 4) immediately after, and 24 h after irradiation. Results : The initial number of breaks in chromosome 4 was proportional to irradiation dose and was identical for all the different human cell lines, irrespective of radiosensitivity. On the other hand, the number of chromosome 4 breaks remaining 24 h after irradiation reflected the radiosensitivity of the cells such that the relationship between residual chromosome aberrations and cell survival was the same for the different cell lines. Conclusions : These results suggest that the scoring of chromosome aberrations in interphase using FISH with PCC holds considerable promise for predicting the radiosensitivity of normal and tumor tissues in situ.