REGULATION OF TUMOR-GROWTH AS A TOTAL MASS IN MICE - APOPTOSIS AS A MAJOR MECHANISM IN ALTERING GROWTH-RATES OF SINGLE AND MULTIPLE COEXISTING TUMOR NODULES

Earlier studies have suggested that a solid tumor behaves, in its gene ral pattern of growth, like a normal integrated organ. in this study, the growth patterns of spherically shaped tumor nodules are re-examine d using an accurate tumor volume-measuring procedure, with the aim of investigating the possible role of apoptosis in regulating tumor growt h. Observations revealed at least three distinct phases of growth: rap id growth phase I, slower growth phase II and 'stationary' phase III. Transition from one phase to the next was primarily due to an increase in the level of apoptosis and not to a decrease in the cell prolifera tion rate. The level of apoptosis, at a given phase, was similar in a single nodule and each of the multiple coexisting nodules of the same tumor line. However, temporal shifts in apoptosis levels caused early phase transition in coexisting nodules, such that their total volume w as the same as that of a single nodule. it can be concluded that apopt osis appears to be a primary mechanism regulating tumor growth as a 't otal mass', irrespective of whether the tumor exists in one or multipl e nodules, if derived from the same tumor line.