THE PROLIFERATIVE CAPACITY OF MOUSE FIBROSARCOMA CELLS THAT SURVIVED X-IRRADIATION

Delayed reproductive death, the appearance of colonies with a reduced cell density (impaired colonies) and the number of giant cells per col ony were investigated in murine fibrosarcoma cells after irradiation w ith 3 to 9 Gy of x-rays. Radiation survivors were replated after reach ing confluence, which occurred after 13 to 15 doublings; this procedur e was repeated three times. The replating efficiency decreased in a do se-dependent manner, the survivors of 9 Gy achieving only 30% of the p lating efficiency of unirradiated cells. After the third replating, i. e. after 40 to 45 doublings, the plating efficiency of the survivors a pproached that of the controls. The median colony size of the survivor s showed a similar dose-dependent decrease, which was pronounced after the first replating but still remained significant after the third re plating. The fraction of impaired colonies was increased to more than 30% in 9-Gy survivors, and though abating, the increase was still sign ificant even after the third replating. Evidence of residual damage wa s also provided by the presence of giant cells. For instance, after 6 Gy irradiation and 13 to 15 doublings, the proportion of colonies with giant cells was 60%, decreasing only to 45% after 40 to 45 doublings. The number of giant cells per colony was 1.4 in colonies arising imme diately after 6 Gy, decreasing to 0.9 after the third replating. These results suggest that the proliferative capacity of surviving cells is depressed even longer than their clonogenic capacity.