Repopulation ability and proliferation stimulus in the hematopoietic system of mice following gamma-irradiation.

The repopulation ability of bone marrow was measured following whole body gamma irradiation of mice. Immediately after irradiation (100--500 rad) bone marrow suspensions were transfused into lethally irradiated syngeneic recipients. At various time intervals after transfusion (1 hour--20 days) DNA synthetic activity in femur and spleen was measured by incorporation of 125iodo-deoxyuridine (125IUdR). The cellularity of femoral bone marrow and the spleen weight was determined. A dose dependent retardation of repopulation was found to be correlated with an increasing duration of an elevated proliferation index (125IUdR-incorporation per unit bone marrow cells of per unit spleen weight, resp.). This suggests that the organism exerted a stimulus on the hematopoietic system to promote regeneration. This proliferation stimulus was kept at a high level unit a certain degree of hematopoietic function was restored either by regeneration of the bone marrow or, by compensating proliferation, in the spleen. The repopulation ability apparently was not only impared by the loss of stem cells but also by the induction of genetic damage in stem cells whose survival and partial functioning may have been enabled by the elevated proliferation pressure.