Pulmonary gene expression profiling of inhaled ricin

Toxicon. 2003 Jun;41(7):813-22. doi: 10.1016/s0041-0101(03)00035-7.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Gene Expression Regulation
  • Lethal Dose 50
  • Lung / drug effects*
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotide Array Sequence Analysis
  • Pulmonary Edema / chemically induced
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ricin / administration & dosage
  • Ricin / toxicity*


  • Aerosols
  • Ricin