Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats.
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.
Monleau
Marjorie
M
IRSN/DRPH/SRBE, Laboratoire de Radiotoxicologie Expérimentale, BP 166, 26702 Pierrelatte Cedex, France.
De Méo
Michel
M
Paquet
François
F
Chazel
Valérie
V
Duménil
Gérard
G
Donnadieu-Claraz
Marie
M
D000818:Animals; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D020552:Comet Assay; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D007220:Industrial Waste; D019570:Inhalation Exposure; D007668:Kidney / Q000166:cytology / Q000528:radiation effects; D008297:Male; D009153:Mutagens / Q000145:classification / Q000633:toxicity*; D011848:Radioactive Pollutants / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism / Q000528:radiation effects; D013047:Specific Pathogen-Free Organisms; D014501:Uranium / Q000633:toxicity*
D016207:Cytokines; D007220:Industrial Waste; D009153:Mutagens; D011848:Radioactive Pollutants; D014501:Uranium; D004247:DNA; D006861:Hydrogen Peroxide