Role of Myelofibrosis in Hematotoxicity of Munition 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) detection of extramedullary hematopoiesis in support of the hypothesis that RDX is toxic to hematopoietic bone marrow stem cells but results with MNX also suggest decreased erythropoietin may compound the myelosuppressive effect and 2) a MNX effect on the bone marrow stromal niche which supports hematopoiesis through expansion of one of its cell types. Collectively these results continue to suggest an early erythroid/myeloid lineage precursor and/or 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, 2008
- Accession Number
- ADA494012
Entities
People
- Sharon A. Meyer
Organizations
- University of Louisiana at Monroe