Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats.
Monleau M, De Meo M, Paquet F, Chazel V, Dumenil G, Donnadieu-Claraz M.
IRSN/DRPH/SRBE, Laboratoire de Radiotoxicologie Experimentale, BP 166, 26702 Pierrelatte Cedex, France.
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.
PMID: 16221956 [PubMed - in process]
