Pulmonary gene expression profiling of inhaled ricin.
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.
DaSilva
Luis
L
Toxinology and Aerobiology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. luis.dasilva@amedd.army.mil
Cote
Dawn
D
Roy
Chad
C
Martinez
Mark
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Duniho
Steve
S
Pitt
M Louise M
ML
Downey
Thomas
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Dertzbaugh
Mark
M
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*
D000336:Aerosols; D012276:Ricin