Accession Number : ADA429500


Title :   Pulmonary Gene Expression Profiling of Inhaled Ricin


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD DIV OF TOXINOLOGY AND AEROBIOLOGY


Personal Author(s) : DaSilvaa, Luis ; Cotea, Dawn ; Roya, Chad ; Martinezb, Mark ; Dunihob, Steve


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA429500


Report Date : 01 FEB 2003


Pagination or Media Count : 11


Abstract : Aerosol exposure to ricin causes irreversible pathological changes of the respiratory tract resulting in epithelial necrosis, pulmonary edema and ultimately death. The pulmonary genomic profile of BALB/c mice inhalationally exposed to a lethal dose of ricin was examined using cDNA arrays. The expression profile of 1178 mRNA species was determined for ricin-exposed lung tissue, in which 34 genes had statistically significant changes in gene expression. Transcripts identified by the assay included those that facilitate tissue healing (early growth response gene (egr)-1), regulate inflammation (interleukin (IL)-6, tristetraproline (ttp)), cell growth (c-myc, cytokine-inducible SH2-containing protein (cish)- 3), apoptosis (T-cell death associated protein (tdag)51, pim-1) and DNA repair (ephrin type A receptor 2 (ephA2)). Manipulation of these gene products may provide a means of limiting the severe lung damage occurring at the cellular level. Transcriptional activation of egr-1, cish-3, c-myc and thrombospondin (tsp)-1 was already apparent when pathological and physiological changes were observed in the lungs at 12 h postexposure. These genes may well serve as markers for ricin-induced pulmonary toxicity. Ongoing studies are evaluating this aspect of the array data and the potential of several genes for clinical intervention.


Descriptors :   *AEROSOLS , *RICIN , REPRINTS , DEOXYRIBONUCLEIC ACIDS , LUNG , T LYMPHOCYTES , INFLAMMATION , GENETIC MAPPING , PULMONARY EDEMA , GENETIC TISSUE IDENTIFICATION.


Subject Categories : BIOCHEMISRTY
      GENETIC ENGINEERING AND MOLECULAR BIOLOGY
      TOXICOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE