Production and Repair of Chromosome Damage in an X-ray Sensitive CHO Mutant Visualized and Analysed in Interphase Using the Technique of Premature Chromosome Condensation

Summary

Production and repair of chromosome damage were studied in interphase xrs-5 cells by means of premature chromosome condensation (PCC). The results obtained were compared with those previously reported for CHO cells. Production of chromosome damage per unit of absorbed radiation dose was in xrs-5 cells larger by a factor of 2·6 than in CHO cells (5·2 breaks per cell per Gy). Changes in chromatin structure, associated with the radiation-sensitive phenotype of xrs-5 cells, that increase the probability of conversion of a DNA double-strand break (dsb) to a chromosome break are invoked to explain this effect. Repair of chromosome breaks as measured in plateau-phase G₁ cells was deficient in xrs-5 cells and the number of residual chromosome breaks was practically identical to the number of lethal lesions calculated from survival data. This observation suggests that non-repaired chromosome breaks are likely to be manifestations of lethal events in the cell. The yield of ring chromosomes scored after a few hours of repair was higher by a factor of three in xrs-5 compared with CHO cells. This increase in ring formation suggests an increase in the probability of misrepair of chromosome damage that may stem either from the reduced ability of xrs-5 cells to repair dsb, or from the higher production of chromosome fragments observed per cell and per Gy.