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 colony were investigated in murine fibrosarcoma cells after irradiation with 3 to 9 Gy of x-rays. Radiation survivors were replated after reaching confluence, which occurred after 13 to 15 doublings; this procedure was repeated three times. The replating efficiency decreased in a dose-dependent manner, the survivors of 9 Gy achieving only 30% of the plating efficiency of unirradiated cells. After the third replating, i.e. after 40 to 45 doublings, the plating efficiency of the survivors approached that of the controls. The median colony size of the survivors showed a similar dose-dependent decrease, which was pronounced after the first replating but still remained significant after the third replating. The fraction of impaired colonies was increased to more than 30% in 9-Gy survivors, and though abating, the increase was still significant even after the third replating. Evidence of residual damage was 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 immediately 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.