Steelʹs potential doubling time and its estimation in cell populations affected by nonuniform cell loss

The in vivo infusion of the thymidine analogue bromodeoxyuridine (BrdUrd), followed by delayed biopsy and bivariate DNA-BrdUrd flow cytometry, makes it possible to estimate Steelʹs potential doubling time (Tpot) of human tumors. In the present paper, the expression of Steelʹs Tpot for a rather general cell population model, in which the distribution of cell loss is assumed to be nonuniform, is derived in terms of the model parameters. We show that Steelʹs Tpot of a population can be markedly different from the doubling time that would be exhibited by the population in the absence of cell loss. These doubling times, on the contrary, are equal when loss is uniform. Moreover, we studied the influence of modes of cell loss different from the uniform random loss on the estimation of Tpot by using the labeling index or the v-function, quantities that can be determined from the bivariate DNA-BrdUrd distribution.