Kinetic models of C3H mouse mammary tumor growth: implications regarding tumor cell loss

Three models of tumor cell loss are described. The effects of cell loss on other cellular kinetic parameters are evaluated, and experiments which may distinguish among the models are discussed. Each model is based on a different cell-loss mechanism, and equations for the cell-cycle, cell-frequency distribution, the growth of both the proliferating and non-proliferating cell population, the growth fraction (GF), and the relative rate of volumetric growth, (dV/dt)/V, are derived. The following types of data are simulated for each model: the pulse labelling index, the mitotic index, and the labeling index as a function of time after a single or a series of 3H-TdR injections. The relative volumetric growth rate has the same mathematical form for each model. The PLM curves predicted by each model for the tumor lines studied (S102F and Slow) are not appreciably different. The predicted initial labeling index and mitotic index may differ significantly among the models depending upon the tumor line. The most striking difference among the models lies in the predictions regarding the labeling index as a function of time after a single or after a series of 3H-TdR injections. These types of labeling experiments should be valuable for distinguishing the different cell-loss mechanisms in solid tumors.