Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2597814 | Toxicology | 2006 | 16 Pages |
We have used global gene expression profiling, combined with pathway analysis tools, to identify in rats the molecular events associated with paraquat toxicity in the lung. Early (2, 8 and 18 h) gene expression changes induced following intraperitoneal (i.p.) exposure to paraquat were measured in the caudal lobe of lungs using Affymetrix rat genome GeneChips (31,042 probe sets). A single high dose of paraquat dichloride (20 mg/kg) was used that has been shown previously to cause in rats extensive lung fibrosis after 10 days. Hierarchical clustering of 543 paraquat-responsive genes (false discovery rate < 0.05) revealed that under these conditions of exposure paraquat induces a staged transcriptional response in the rat lung that precedes the appearance of lung damage. We report here that many of the transcriptional responses to paraquat were rapid (being maximal at 2 h post-dose), and that the predominant molecular functions and biological processes associated with these genes include membrane transport, oxidative stress, lung development, epithelial cell differentiation and transforming growth factor β (TGF-β) signalling. These data provide novel insights into the molecular pathways that lead to toxicity after exposure of the rat lung to paraquat.