Studies on the hyperthermic sensitivity of the murine hematopoietic stem cell compartment. I. Heat effects on clonogenic stem cells and progenitors.

The heat sensitivity at 42 degrees, 43 degrees and 44 degrees C of various hematopoietic subsets in murine bone marrow (MRA, CFU-S-12, CFU-S-8, CFU-GM, BFU-E and CFU-E) was investigated in order to determine whether there is a relationship between heat sensitivity and the position of cells within the stem cell hierarchy. The results show that the primitive stem cell with marrow repopulating ability (MRA) is extremely heat-resistant compared with the most differentiated hematopoietic progenitor (colony-forming unit-erythroid [CFU-E]). The proliferative activity of the hematopoietic subsets was determined from the number of cells killed by hydroxyurea (HU). It is demonstrated that there is a progressive increase in the proportion of hematopoietic subset cells in S-phase with maturation. The various heat sensitivities among the different hematopoietic subsets appear to be related to their proliferative activity. This relationship may have relevance to the clinical application of hyperthermia as a purging modality.