Pro-oxidant responses of respiratory cells to organic dust extracts.
Cosma-G; Martinez-A; Ufferfilge-D; Vallyahan-V
Toxicologist 1997 Mar; 36(1)(Part 2):297-298
We have developed a two-compartment cell model to explore the pathways of pro-oxidant injury in respiratory epithelial and alveolar macrophage (AM) cell lines exposed to organic dust extracts. The purpose of these studies is two-fold: 1) identify major toxic components of these complex dusts; and 2) define the underlying mechanisms of pro-inflammatory cell injury and adaptation in lung. The following responses were examined: 1) AM activation-respiratory burst; 2) cytokine production; 3) oxidative DNA damage; and 4) stress protein induction. Our evidence suggests that lung cells respond in a qualitatively, but not quantitatively, similar fashion following exposures to grain dust extracts vs. purified endotoxin, suggesting the participation of other agents in toxic responses of lung to organic dusts. AM cells demonstrated a rapid pro-oxidant response to dust extracts, including production of hydrogen peroxide and interleukin-l as detected by immunoassay, which was followed 24 hr later by single-stranded DNA damage as measured by gel electrophoresis and immunoassay. This initial DNA damage resolved 48 hr later. Antioxidants such as catalase (500U/ml) and N-acetylcysteine (20 mM) provided only partial protection against these pro-oxidant responses. Epithelial cells lacked the pro-oxidant responses, but did display DNA damage after prolonged 3 day exposures. AM cells, but not epithelial, demonstrated, a rapid induction of metallothionein (MT) and heme oxygenase (HO) gene expression following exposures to dust extracts as measured by mRNA blot analyses. These data support a role for oxidative injury to respiratory cells following exposures to particulates, and potential protective responses by stress proteins. Reactive oxygen species-induced activation of DNA binding protein NF-kappaB and antisense MT/HO studies are ongoing.
Toxic-materials; Toxins; Exposure-assessment; Exposure-levels; Exposure-limits; Alveolar-cells; Lung-cells; Lung-disease; Lung-irritants; Lung-tissue; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system-disorders; Dust-exposure; Cell-damage; Cell-cultures
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 2006, Cincinnati, Ohio