Predicted dose-latency relationships for early- and late-responding hierarchical tissues

Theoretical dose-latency relationships for the time to manifestation of radiation injury in a hierarchical (type H) tissue were investigated using mathematical modelling. Observable tissue injury was assumed to correspond to depletion of cells in the functional compartment to a critical level. The results illustrate that the latent times of an early-responding type H tissue can be dose-dependent, although the difference between the maximum and minimum latent times is fairly small; the dose-dependence occurs because the dose affects the rate at which cells enter the functional compartment from the proliferative compartment while the functional cells are initially shed from the tissue at a rate that is independent of dose, resulting in a net dose-dependence of functional cell loss. Dose-dependent latent times were also obtained for a hypothetical late-responding type H tissue, but the dose-dependence was much more pronounced than for the acutely responding tissue; the difference in latent times was nearly 3 months over a dose range of a few Gy. This illustrates that the experimentally observed dose-latency relationships for late-responding normal tissues, which have unknown renewal characteristics, are not inconsistent with the hypothesis that those tissues have a hierarchical tissue structure similar to that of early-responding tissues. The dose-latency relationship for early responses was influenced most strongly by the characteristics of the transit cells, whereas for the late responses it depended mainly on the characteristics of the stem cells. Residual injury in both early and late-responding tissues can be modelled on the basis of permanent depletion of the stem cell compartment, e.g. via depletion of the number of tissue-renewal units.