The study of granulocyte kinetics by mathematical analysis of DNA labelling

Summary A commonly used experimental procedure for the study of granulocyte kinetics involves the labelling and subsequent tracing of granulocyte DNA. Following the introduction of a label into the system, observations are made periodically on the concentration of label in the DNA of granulocytes taken from the circulating blood. A mathematical model for the expected value of this concentration (expressed as a function of time following label introduction) has been derived, studied, and related to experimental observations from studies using P³² as a label. Insofar as the derivation of the model accurately incorporates the relevant aspects of granulocyte kinetics, the model will be useful in the interpretation of the experimental observations in terms of these kinetics.Among other things, study of the model indicates that the assumption of flash labelling made with respect to some labels is quite crucial and needs to be examined critically. It has also been necessary to make adjustments to allow for the observed emergence of labelled cells from the marrow soon after label introduction. In addition, despite a high degree of confounding of parameter effects it has been possible to suggest bounds on some of the parameters of the model for some species. The bounds will be refined as the model is improved and more data become available. Study and development of the model continues with particular interest in generalizations to include the diseased state chronic granulocytic leukemia.This work was presented in part to the Annual Meeting of the Institute of Mathematical Statistics, The American Statistical Association and The Biometric Society, Washington, D. C. December 1967.Dr.Walker is the recipient of Research Career Development Award 1 —K3 —CA —9554 from the National Cancer Institute.