CELL KINETICS OF IRRADIATED EXPERIMENTAL TUMORS: CELL TRANSITION FROM THE NON-PROLIFERATING TO THE PROLIFERATING POOL

Abstract

Parenchymal tumor cells of murine mammary carcinomas can be divided into 2 pools, using nucleoli as morphological markers. Cells with dense nucleoli traverse the cell cycle and divide, thus constituting the proliferating pool. Cells with trabeculate or ring-shaped nucleoli proceed slowly through G1 phase or are arrested in it. The role of these nonproliferating, G1 phase-confined cells in tumor regeneration was studied in vivo after a subcurative dose of X-irradiation in 2 transplantable tumor lines. Tumor-bearing mice were continuously injected with methyl[3H]thymidine before and after irradiation. The labeling was discontinued, mice were injected with vincristine sulfate and cells arrested in metaphase were accumulated over a 10 h period. Two clearly delineated groups of vincristine-arrested mitoses emerged in autoradiograms prepared from tumor tissue at the time of starting tumor regrowth: 1 group with the silver-grain counts corresponding to the background level, the other with heavily labeled mitoses. As the only source of unlabeled mitoses was unlabeled G1 phase-confined cells persisting in the tumor, this observation indicated cell transition from the nonproliferating to the proliferating pool, which took place in the initial phase of the tumor regrowth. Unlabeled progenitors have apparently remained in G1 phase for at least 5-12 days after irradiation.