Role of Myelofibrosis in Hematotoxicity of Munitions RDX Environmental Degradation Product MNX
Annual rept. 31 Aug 2008-30 Aug 2009
LOUISIANA UNIV AT MONROE
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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 munition hexahydro-1,3,5-trinitro-1,3,5-triazine RDX, causes anemia after acute exposure in the rat and examine whether similar effects were elicited by subchronic exposure. We have hypothesized MNX targets hematopoeitic stem cells and, like other myelosuppre-sive chemicals, will be fibrogenic to bone marrow. During this reporting period, results from subchronic exposure in which rats were treated orally with LD50 MNX daily for 4 or 6 weeks were 1 significant increases in granulo-cytes and platelets, but not erythrocytes, at both times, 2 an increase in serum K and decreases in Na, Cl, glucose, and creatinine levels in the absence of effect on body weight gain and serum albumin, 3 increased liver weights and 4 increased megakaryocytes in bone marrow, but not fibrosis as indicated by methenamine silver stain for reticulin fibers. Collectively, these results continue to support a bone marrow effect of MNX upon subchronic exposure that is consistent with impaired hematopoiesis and identify additional non-marrow targets. These results suggest that MNX toxicity in the rat may resemble the prefibrotic phase of the myeloproliferative disorder, idiopathic myelofibrosis, and thus may offer a model for study of disease progression and intervention strategies.
- Medicine and Medical Research
- Ammunition and Explosives