Uranium is an alpha-particle-emitting heavy metal. Its genotoxicity results from both its chemical and its radiological properties that vary with its isotopic composition (12% enriched uranium in (235)U (EU) has a specific activity 20 times higher than 0.3% depleted uranium in (235)U (DU)). The influence of the isotopic composition of uranium on its genotoxic profile (clastogenic/aneugenic) has never been described. The present study evaluated genotoxic profile of uranium with the cytokinesis-block micronucleus centromere assay. C3H10T1/2 mouse embryo fibroblasts were contaminated with either DU or EU at different concentrations (5 microM, 50 microM and 500 microM). Cells received low doses ranging from 0.3 microGy to 760.5 microGy. The frequency of binucleated cells with one micronucleus increased with increasing concentrations of both DU and EU in the same way. EU induced more centromere-negative micronuclei and nucleoplasmic bridges than DU. A correlation between these two clastogenic markers and ionizing radiation doses was observed. Finally, this study showed that the genotoxic profile of uranium depends on its isotopic composition. DU and EU are low and high clastogens, respectively. However, DU aneugenic effects remain high. Thus, there is a need to study the potential role of aneugenic effects of DU in carcinogenic risk assessment linked to uranium internal exposure.
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