Hemopoietic progenitor cells in the blood as indicators of the functional status of the bone marrow after total-body and partial-body irradiation: experiences from studies in dogs

Abstract

The granulocyte-macrophage colony-forming cells (GM-CFC) were studied in the blood of dogs to evaluate their relationship to the bone marrow GM-CFC under normal conditions and their involvement in hemopoietic regeneration after different types of exposure to ionizing radiation. The GM-CFC could be defined as regular blood elements showing characteristic levels of their concentration in individual dogs in the range from 20 to 300 cells per ml. In relative terms, the GM-CFC numbers present in the whole blood of normal dogs were found to be on the order of 0.1% of the GM-CFC numbers present in the bone marrow. A small fraction of the GM-CFC population in the bone marrow, i.e., about 1%, can be mobilized into the peripheral blood within three h by intravenous injection of dextran sulfate (DS). These cells are characterized by a small size and a low S-phase fraction similar to the GM-CFC that are normally present in the blood. Total-body irradiation with single doses of 0.8 Gy and more caused a characteristic pattern of sequential changes in the blood GM-CFC concentration that were related to the recovery of the bone marrow GM-CFC population. The blood GM-CFC concentration showed an extreme depression within the first 15 days, a transient increase from day 17 to day 35 and remained at subnormal values for several weeks and months. The regeneration of the GM-CFC population in the bone marrow that could be mobilized into the blood by DS was similarly delayed as the recovery of the blood GM-CFC values. In dogs which were kept under continuous radiation exposure (0.019 Gy/day) causing permanent damage to the hemopoietic system, the GM-CFC numbers in the blood remained permanently depressed. Partial-body irradiation of dogs with a myeloablative dose (11.7 Gy) given to the anterior part of their body was followed by sequential changes in the blood GM-CFC concentration specific for this type of exposure. The pattern of changes was determined by direct radiation effects, the compensatory responses in the protected bone marrow and the regeneration events in the irradiated bone marrow. On the other hand, it could be shown that the repopulation and the restoration of the hemopoietic tissue is initiated by the seeding of hemopoietic cells (including GM-CFC) from the protected marrow.