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Age-specific Changes in the Proliferation of Ehrlich Ascites Tumor Cells Grown as Solid Tumors¹

Department of Anatomy, McGill University, Montreal, Quebec, Canada

Reasons for a deceleration of the growth rate with increasing age of the solid tumors obtained with s.c. transplantation of 10⁷ cells form Ehrlich ascites tumors in the same strain mice were investigated with the aid of thymidine-³H labeling and radioautography. While the doubling time of the tumor mass, exclusive of necrotic tissue, changed from 82 hr at 6 days to 204 hr at 14 days and to 492 hr at 26 days, the median duration of the tumor-cell cycle (measured from temporal changes in the percentage of labeled mitoses after a single injection of thymidine-³H) showed only a small change (from 16.4 to 17.8 and 18.3 hr, respectively). The fraction of proliferating cells, measured as the ratio of the observed fraction synthesizing DNA to the expected fraction in DNA synthesis if all the cells were in cycle, declined from a value of 0.44 at 6 days to 0.37 at 14 days and 0.32 at 26 days. The rate of cell death in the viable portion of the tumor, measured as the discrepancy between the production rate and the growth rate, remained close to 1.4%/hr at all the ages. However, the cell death factor (, the ratio of the extent of cell death to that of cell production) showed a remarkable increase.

Overall growth rate of the tumor was faster than that of the viable portion because of a decline in the rate of removal of necrotic tissue. The latter, measured as the discrepancy between the rate of inflow of dead cells into the necrotic compartment and the growth rate of this compartment, changed from 0.68%/hr at 6 days to 0.50%/hr at 14 days and 0.42%/hr at 26 days. However, the overall rate of cell removal, expressed as a percentage of the whole tumor, remained unchanged (approximately 0.3%/hr), although the cell loss factor (, the ratio of the extent of cell loss to that of cell production) showed a progressive increase. Cell disposal factor (, the ratio of the extent of cell removal to that of cell death) increased with time but never reached 100% value, thus indicating a continued growth of necrotic tissue.

Within an individual solid tumor, zones of high growth fraction were often associated with proximity to capillaries.

Present findings in the solid tumor contrast to those in the ascites from, where a growth retardation results primarily from a rapid prolongation of the cell cycle time, and to a lesser extent from a moderate decline in the proliferating fraction and a slow increase in the rate of cell loss.

¹ Financial support by the National Cancer Institute of Canada and the Medical Research Council of Canada is gratefully acknowledged.

Received 8/18/71. Accepted 12/ 9/71.