Speciation-dependent cellular uptake and cytotoxicity of tri- and tetravalent lanthanides and actinides in/onto mammalian kidney cells

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The general aim of the proposed project is to expand and improve the insufficient knowledge about the transfer of tri- and tetravalent actinides and lanthanides into mammalian cells. Investigations are performed at the trace concentration level each with one representative of stable tri- and tetravalent actinides, i. e. Cm(III)/Am(III) and Pu(IV), as well as Ce(III, IV) as the respective lanthanide analog. Due to the excretion of these elements via the kidneys during the first 24 hours, selectively mammalian kidneys cells are studied in the proposed project. One specific goal is to explore the cellular uptake of these elements, their accumulation on the cell surface and their cytotoxicity. These investigations will be performed in dependence on the speciation of an element, i. e., the oxidation state, metal ion concentration, and counter ion, as well as in dependence on the incubation time. Theoretical modeling and experimental studies on the speciation of the selected elements in a relevant biofluid, i. e., human urine, and different cell culture media serve as a supporting basis for this. Another aspect of the proposed project is to determine the similarities and/or differences of the biological and biochemical behavior of 4f and 5f elements with the same oxidation state and, thus, to check the actinide lanthanide analogy in the field of biochemistry. The results of the proposed project will provide previously unknown thermodynamic complex stability constants of Pu, Cm/Am, and Ce with biological relevant ligands. Theses data contribute to an expanded data base and facilitate more reliable future modeling of the speciation of tri- and tetravalent actinides and lanthanides in body fluids and cell culture media. Furthermore, numerical values for the cellular uptake of these elements, their accumulation on the cell surface and the rate of vitality for the exposed kidney cells will be determined. These data contribute to a more profound knowledge of the biochemical processes involved into the cellular uptake and toxicity of actinides and lanthanides. In future, this may also contribute to the development of new specific decontamination procedures and decorporation agents.