Haemopoietic injury after irradiation: analysis of dose responses and repair using a target-cell model

Published dose-incidence data for haemopoietic lethality in mice have been analysed using a mathematical model based on target-cell survival. The analysis of three comprehensive data sets produced an initial D(o) value of about 1.4 Gy, decreasing to about 1.1 Gy at 3 Gy, 0.9 Gy at 5 Gy, and about 0.7 Gy at a dose of 10 Gy. The alpha/beta ratio was about 14 Gy, and the repair half-time was about 0.3 h. The level of target-cell depletion at LD37 was at about 6 x 10(-4). The D(o) values are compatible with those measured directly for several stages of early haemopoietic progenitor cells in the marrow. The additional use of 13 or alternatively 24 other less-comprehensive data sets increased the overall degree of heterogeneity, so flattening dose-response curves and increasing the deduced overall D(o) values by a factor of about 2. However, when these data sets were stratified with respect to ln(N(o)) where N(o) is the number of tissue rescuing units (TRU), the results were comparable to those obtained when the three comprehensive data sets were analysed individually. Also, the repair halftime was higher at about 1 h. Further, the implied radiosensitivity of the projected target-cell population comprising the TRU was similar to the survival curves obtained for CFU-S and other closely-related haemopoietic progenitor cell types. It has been shown that the number of critical TRU at risk in the marrow is the main feature modulating heterogeneity even when it is assumed that the cellular radiosensitivity does not vary between strains. The number of stem cells comprising a TRU may vary between strains and this may also be influenced by environmental and/or immunological factors. However, it is certainly the case that the initial complement of TRU plays a major role in the incidence of whole body radiation induced mortality.