Evidence of isotopic fractionation of natural uranium in cultured human cells

Significance In vivo isotopic fractionation studies of metals in living organisms have recently revealed an outstanding potential for biomedical and toxicological studies. In vitro studies in cellular models are underexploited, although they have the potential to provide invaluable information to understand the processes at the origin of such isotopic fractionations. This work demonstrates the isotopic fractionation of natural uranium during its uptake by neuron-like human cells. The direction of isotopic fractionation provided clues for the identification of potential U incorporation pathways into cells, unknown until now. These findings open new perspectives on the use of isotopic fractionation of metals in cellular models for the investigation of metabolic processes, the identification of new biomarkers, and the interpretation of clinical results.