Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats
Résumé
Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation. © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Mots clés
Specific Pathogen-Free Organisms
Uranium
Animalia
cytokine
hydroperoxide
uranium
uranium dioxide
animal cell
animal experiment
animal model
animal tissue
article
comet assay
controlled study
correlation function
DNA damage
DNA strand breakage
genotoxicity
in vivo study
inflammation
kidney cell
lung alveolus cell
lung toxicity
male
nephrotoxicity
nonhuman
oxidative stress
protein expression
radiation dose
radiation exposure
rat
solubility
Animals
Bronchoalveolar Lavage
Bronchoalveolar Lavage Fluid
Comet Assay
Cytokines
DNA
DNA Damage
Epithelial Cells
Gene Expression
Hydrogen Peroxide
Industrial Waste
Inhalation Exposure
Kidney
Male
Mutagens
Radioactive Pollutants
Rats
Sprague-Dawley
Respiratory Mucosa