Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium

Authors: Miller, Alexandra¹; Bonait-Pellie, Catherine²; Merlot, Robert²; Michel, John²; Stewart, Michael³; Lison, Paul²

Source: Molecular and Cellular Biochemistry, Volume 279, Numbers 1-2, November 2005 , pp. 97-104(8)

Publisher: Springer

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Abstract:

Depleted uranium (DU) is a dense heavy metal used in military applications. During military conflicts, US military personnel have been wounded by DU shrapnel. The health effects of embedded DU are unknown. Published data from our laboratory demonstrated that DU exposure in vitro can transform immortalized human osteoblast cells (HOS) to the tumorigenic phenotype. Results from our laboratory have also shown that DU is genotoxic and mutagenic in cultured human cells. Internalized DU could be a carcinogenic risk and concurrent alpha particle and heavy metal toxic effects complicate this potential risk. Anecdotal reports have suggested that DU can cause leukemia. To better assess this risk, we have developed an in vivo leukemogenesis model. This model involves using murine hematopoietic cells (FDC-P1) that are dependent on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin 3 (IL-3) and injected into mice to produce myeloid leukemia. Although immortalized, these cells are not tumorigenic on subcutaneous inoculation in mice. Intravenous injection of FDC-P1 cells into DU-implanted DBA/2 mice was followed by the development of leukemias in 76% of all mice implanted with DU pellets. In contrast, only 12% of control mice developed leukemia. Karyotypic analysis confirmed that the leukemias originated from FDC-P1 cells. The growth properties of leukemic cells from bone marrow, spleen, and lymph node were assessed and indicate that the FDC-P1 cells had become transformed in vivo. The kidney, spleen, bone marrow, muscle, and urine showed significant elevations in tissue uranium levels prior to induction of leukemia. These results demonstrated that a DU altered in vivo environment may be involved in the pathogenesis of DU induced leukemia in an animal model.

Keywords: DBA; depleted uranium; heavy-metals; internal exposure; leukemia; mice

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s11010-005-8226-z

Affiliations: 1: Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research, Institute, Bethesda, Maryland, USA, Email: millera@afrri.usuhs.mil 2: Department of Occupational and Environmental Medicine, University of Paris, Paris, France, 3: Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research, Institute, Bethesda, Maryland, USA,

Publication date: 2005-11-01

Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium

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