Tissue population configuration as a modifier of organ dose response

Organ tissue populations exist in different spatial configurations. There are the idealized "volume" configuration (bone marrow), the "monolayer" (skin basal cell or large vessel endothelial populations), the "linear" (microvascular endothelial populations) and the "isolated unit" (capillaries, intestinal crypt). This defines the size of the irradiated population (No) and influences the absolute number of cells (N) that survive per unit of tissue dimension to permit repopulation. A proliferative cell that survives irradiation replaces cells lost from distant locations according to its spatial dimension. However, in the isolated unit configuration, a proliferative cell can replace those cells lost from the unit, but an anatomical barrier prevents cell replacement extending to adjacent units. Recovery of a tissue following irradiation depends not only on the number of surviving proliferative cells, but also on the organization of those cells into sub-populations. A regenerative unit is a subpopulation capable of being regenerated from the survival of a single cell. A tissue "functional unit" is a subcomponent of the tissue which contributes independently to overall tissue function, and whose loss results in an irreversible incremental loss of function. Survival of the functional unit depends critically on the degree of interdependence among component regenerative units, and such interdependence is strongly influenced by the tissue's spatial organization. Using these concepts, a mathematical formulation expresses a tissue's functional response to irradiation in terms of cell survival parameters, the spatially-related parameters of regenerative unit size, and the number of interdependent regenerative units comprising a functional unit. It is argued that this provides a more realistic approach toward simulating the radiation response of an organ than one based on tissue bulk cell survival parameters alone.