title: Pulmonary gene expression profiling of inhaled ricin.
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.
authors.affiliation: Toxinology and Aerobiology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. luis.dasilva@amedd.army.mil
authors.forename: Luis
authors.initials: L
authors.lastname: DaSilva
authors.forename: Dawn
authors.initials: D
authors.lastname: Cote
authors.forename: Chad
authors.initials: C
authors.lastname: Roy
authors.forename: Mark
authors.initials: M
authors.lastname: Martinez
authors.forename: Steve
authors.initials: S
authors.lastname: Duniho
authors.forename: M Louise M
authors.initials: ML
authors.lastname: Pitt
authors.forename: Thomas
authors.initials: T
authors.lastname: Downey
authors.forename: Mark
authors.initials: M
authors.lastname: Dertzbaugh
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D005786:Gene Expression Regulation; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D011654:Pulmonary Edema / Q000139:chemically induced; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012276:Ricin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000336:Aerosols; D012276:Ricin