Influence of location within a tumor on cell survival as measured by a clonogenic assay.

In order to elucidate the influence of the location of a cell within a tumor on cell survival, 12 to 16 samples from an individual 9L s.c. tumor were assayed for colony formation. These samples (4 to 6 mg) were taken from untreated, heated, or irradiated tumors, and the variances of the mean relative colony-forming efficiency (RCFE) for individual tumors or groups of similarly treated tumors were compared. These comparisons allowed determination of the effect of location and treatment on the intratumor variability in cell survival. Three factors can influence variability of the RCFE's across tumors: (a) inherent differences in clonogenic capacities; (b) unequal dose distribution of the treatment agent, and (c) different sensitivities of cells to the treatment. Considerable variability was found in the cell survival of control tumors, and treatment of tumors in air-breathing or nitrogen-asphyxiated rats with X-rays did not change the magnitude of this variability. However, the variance of the mean RCFE of heated tumors was an order of magnitude greater than that observed in either control or irradiated tumors. Of the three possible factors that could influence cell survival within a tumor, all were shown to contribute to the variances of the mean RCFE measured in 9L s.c. tumors. However, our study demonstrated that the relative contribution of each of these factors to the variance will probably depend on the treatment agent(s).