A mathematical model for analysing cellular age-response functions in terms of physiological age

A mathematical model is presented which facilitates the analysis of cellular age-response functions in terms of the physiological ages of the cells. Age-response functions are generally determined by obtaining synchronous cohorts of cells and measuring the sensitivity of the cohorts to the treatment agent at different times after selection (i.e., several different chronological ages). The model described here uses data on the [3H]TdR labelling patterns of the cell population to determine the distribution of physiological ages for the cohorts at the times of treatment. The age-response function data are then analysed in terms of the physiological ages of the cells. The compartments used in the analysis may be chosen according to the biology of the system and the wishes of the experimenters and not imposed by the variability of the phase durations. The application of the model is illustrated using the age-response functions for EMT6 cells exposed to radiation and HeLa cells exposed to hydroxyurea.