Role of Myelofibrosis in Hematotoxicity of Munitions RDX Environmental Degradation Product MNX
Abstract
The purpose of this research is to determine mechanisms through which hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), environmental degradation product of high energetic munition hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), causes persistent anemia in the rat. We have hypothesized MNX targets hematopoeitic stem cells and, like other myelosuppressive chemicals, will be fibrogenic to the bone marrow. Findings of this period are: 1) the inability of RDX and MNX to directly oxidize hemoglobin ferrous iron to methemoglobin in vitro and of MNX to produce methemoglobin in MNX-treated rats, an alternative mechanism for the observed anemia and 2) nitramine targeting of an early multipotential bone marrow stem cell at earlier times after exposure (7d) and flow cytometric assessment of myeloid and erythroid lineage precursors. Collectively, these results continue to suggest an early erythroid/myeloid lineage precursor and/or to the bone marrow stromal niche supporting hematopoiesis as the target of MNX and RDX. These results suggest that MNX- and RDX toxicity in the rat appears to mimic some clinical manifestations of the myeloproliferative disorder, idiopathic myelofibrosis, and thus may offer a model for study of disease progression and intervention strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA474705
Entities
People
- Sharon A. Meyer
Organizations
- University of Louisiana at Monroe