Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apoptosis-dependent and -independent mechanisms

• Published in: Experimental hematology 2003-12, Vol.31 (12), p.1348-1356
• Main Authors: Meng, Aimin, Wang, Yong, Brown, Stephen A, Van Zant, Gary, Zhou, Daohong
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - radiation effects; Busulfan - adverse effects; Cell Survival; Cells, Cultured; Hematopoiesis - drug effects; Hematopoiesis - radiation effects; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - radiation effects; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - radiation effects; Mice; Mice, Inbred C57BL; Radiation, Ionizing; Time Factors; Transplantation Conditioning - adverse effects
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2003.08.014

Ionizing radiation (IR) and busulfan (BU) are commonly used as preconditioning regimens for bone marrow transplantation (BMT). We examined whether induction of apoptosis in murine bone marrow (BM) hematopoietic cells contributes to IR- and BU-induced suppression of their hematopoietic function. The hematopoietic functions of hematopoietic stem cells (HSCs) and progenitors were analyzed by the cobblestone area-forming cell (CAFC) assay. Apoptosis was determined by measuring 3,3′-dihexyloxacarbocyanine iodide (DiCO 6) uptake, annexin V staining, and/or sub-G 0/1 cells. Four cell types were studied: murine BM mononuclear cells (BM-MNCs), linage-negative hematopoietic cells (Lin − cells), Lin − Scal + c-kit + cells, and Lin − Scal − c-kit + cells by flow cytometry. Exposure of BM-MNCs to IR (4 Gy) or incubation of the cells with BU (30 μM) resulted in a significant reduction in CAFC frequency ( p