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ToxSci Advance Access originally published online on October 12, 2005
Toxicological Sciences 2006 89(1):287-295; doi:10.1093/toxsci/kfj010
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genotoxic and Inflammatory Effects of Depleted Uranium Particles Inhaled by Rats

Marjorie Monleau*, Michel De Méo{dagger}, François Paquet*, Valérie Chazel*, Gérard Duménil{ddagger} and Marie Donnadieu-Claraz*,1

* IRSN/DRPH/SRBE, Laboratoire de Radiotoxicologie Expérimentale, BP 166, 26702 Pierrelatte Cedex, France; {dagger} Laboratoire de Biogénotoxicologie et mutagenèse environnementale, Université de la Méditerranée, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille, France; and {ddagger} Laboratoire de Microbiologie, Université de la Méditerranée, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille, France

Received August 5, 2005; accepted September 28, 2005

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.

Key Words: uranium; inhalation; acute-exposure; repeated-exposure; genotoxicity; inflammation.


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