Theory of Radiation Injury and Recovery in Self-Renewing Cell Populations

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Abstract
Models of mammalian [chick] radiation lethality and recovery are developed, based on known or assumed properties of self-renewing tissue cell populations. The models incorporate the fact that unconstrained population growth proceeds at a rate proportional to the cell number. Growth within the organism is constrained in various ways so that the several cell populations attain characteristic stationary sizes. The rate of growth is therefore a product of 2 terms, one of which is a monotone function of attained population size and the other a monotone function of the discrepancy between attained size and limiting size. In the simplest one compartment case this leads to the classic Pearl- Verhulst logistic equation for population growth or recovery. In the past, mammalian recovery processes were usually modeled as lst-order reactions. However, several recent experiments on the effects of split or fractionated exposures have yielded the result that the amount of recovery per day, measured in rads, is constant. This would seem to imply a zero-order recovery process, and such models have in fact been proposed, but they are not very plausible from the point of view of cellular dynamics. It is shown that the logistic model, which has its basis in cell population kinetics, also yields a linear dose-time relation. The model is applied to data on survival after split doses, multiple fractionation, and protracted continuous exposure.

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