Cell kinetics of irradiated experimental tumors: relationship between the proliferating and the nonproliferating pool

The role of nonproliferating cells in tumor regeneration has been studied after subcurative doses of low L.E.T. irradiation. Radiation was applied in a single dose at three different levels; 0-47, 0-94 and 1-88 krad. Studies included estimation of the absolute number of cells per tumor, differential cell counts, and autoradiographic determination of kinetic variables, employing transplantable mouse mammary adenocarcinoma DBAH. Quantitative changes of morphologically defined proliferating and nonproliferating cell pools were followed at different time intervals after irradiation. Irradiation resulted in reduction of the number of cells in both pools, with apparent sparing of nonproliferating cells. The regenerative period started with a gradual increase in the number of cells in the proliferating pool, whereas the number of cells in the nonproliferating pool continued to fall in tumors irradiated with 0-94 and 1-88 krad. In the late phase of tumor regrowth, the increasing number of cells in the non proliferating pool corresponded to its replenishment by cell transition from the proliferating pool. In an effort to clarify whether cell transition from the nonproliferating to the proliferating pool may take place during the regrowth of radiation perturbed tumors, cell loss rates from both pools were estimated using experimental data. In addition to cell loses from the tumor as a whole, the 'net loss rate' of the nonproliferating pool reflects the rate of cell transition from the nonproliferating to the proliferating pool, minus the rate of transition in the opposite direction. A similar definition applies to cell loss rates from the proliferating pool. The results showed: (1) high losses in both pools, with excess losses in the proliferating during the early phase after irradiation; (2) in the early stage of regrowth after irradiation, the cell net loss rate f-or the nonproliferating pool increased, in contrast to the behavior of cell loss rate for the proliferating pool and the average cell loss rate for the tumor as a whole; (3) in the late stage of regrowth a decrease in net loss rate for the nonproliferating pool reflects the excess production of nonproliferating cells over control tumors. These results suggest that cell transition from the nonproliferating to the proliferating pool takes place at the beginning of tumor regrowth after subcurative single-dose irradiation.