Effect of Continuous, Whole-Body Gamma Irradiation upon Canine Lymphohematopoietic (CFU-GM, CFU-L) Progenitors and a Possible Hematopoietic Regulatory Population

Abstract

Clonogenic assays for granulocytes-macrophages (CFU-GM) in bone marrow and for T lymphocytes (CFU-L) in peripheral blood were performed on dogs continuously exposed to 60Co irradiation (0.02, 0.04, or 0.11 Gy/day). When decreased numbers of CFU-GM were observed they correlated well with the clinical status of the dogs but were not generally associated with increasing cumulative doses of absorbed irradiation. In clinically normal, irradiated animals, decreased CFU-GM values and myeloid-erythroid ratios were observed, suggesting that chronic irradiation may affect the granulocytic series well before decreased peripheral blood values are seen. In hypocellular dogs the number of CFU-GM were significantly decreased compared to values obtained from control or clinically normal irradiated dogs, while virtually no CFU-GM were observed in the leukemic dogs. Only the CFU-GM values of the hypocellular group showed an association, e.g., a suggestion of an abortive regenerative effort, with increasing absorbed dose. Proliferative capacity of T lymphocytes (CFU-L) was not affected by either increasing absorbed irradiation or the presence of leukemia. D0 values were determined on marrow fibroblastic cells to ascertain whether a radioresistant subpopulation of stromal elements would result from continuous in vivo irradiation. No correlation was found between absorbed dose and increased D0 values. However, seven of eight dogs which developed acute nonlymphocytic leukemia displayed marrow fibroblastic cells with elevated D0 values. These radioresistant marrow fibroblastic cells were assayed for their ability to support normal granulopoiesis and found to be not significantly different from control fibroblasts.

Pim-1 kinase protects hematopoietic FDC cells from genotoxin-induced death

“…Indexed by asterisks (*) are non-speci®c stained proteins, which also verify clear fractionation of nuclear vs cytoplasmic components In contrast, Pim-1 acts in proliferating hematopoietic progenitor cells to e ciently inhibit PCD due to Co 60 , or adriamycin (see Figure 4). The signi®cance of these results is underlined by the common use of these agents to treat cancers (Klein et al, 1985;Siu et al, 1999) and by the speculation that their e ective doses against hematopoietic targets might be lessened if either Pim-1 or its co-acting factors could be inhibited. Despite intensive research, relatively little is understood as to how either ionizing radiation or anthracyclines link to apoptotic machinery (e.g., caspases).…”

Survival of Erythroid Burst-Forming Units and Erythroid Colony-Forming Units in Canine Bone Marrow Cells Exposed in Vitro to 1 MeV Neutron Radiation or X Rays

“…Beagle dogs are valuable as large animal models for hematopoietic studies of bone marrow transplantation (1) and radiation injury (2)(3)(4). There are a number of reports describing the effects of radiation injury and other regimens on the survival and recovery of GM-CFC and CFU-E in bone marrow from treated dogs (3,4).…”