Early repair processes in marrow cells irradiated and proliferating in vivo.

The radiation survival curves for the proliferative capacity of mammalian cells, both in vitro (1, 2) and in vivo (3, 4), are sigmoidal, suggesting that loss of proliferative capacity involves an accumulation of radiation damage. For mammalian cells in culture, Elkind and co-workers (5, 6) have demonstrated that accumulated sublethal damage may be rapidly repaired in surviving cells, by means of experiments in which the number of survivors was shown to increase when the radiation dose was given as two fractions separated by an interval of time. They have termed this phenomenon "recovery" (5, 7), and Elkind (7) has used the results obtained with cell cultures to predict the outcome of dose-fractionation experiments in vivo. Recently, it has been shown that recovery occurs in irradiated tumor cells in vivo (8). There has, however, been no direct experimental evidence confirming the existence of recovery in normal cells in vivo. The finding (4) that normal mouse bone marrow contains cells capable of forming macroscopically visible colonies in the spleens of heavily irradiated animals provides a quantitative approach to this problem. An important advantage of the spleen-colony technique is that it may be used to study directly the effects of radiation on cells in vivo (9). In this paper, we report the results of dose-fractionation experiments carried out in this system. The results indicate that early repair of sublethal damage occurs in colony-forming cells irradiated in vivo, but suggest that the time scale of the early repair process differs from that observed for cells in culture.