Binding of plutonium and americium to small molecular weight ligands favors their paracellular transfer across lung epithelium in vitro

Abstract

Pulmonary absorption is a critical step in the time-dependent processes governing actinide biodistribution and toxicity following internal contamination by inhalation. The current study was undertaken to investigate on a simple in vitro Calu-3 model the mechanisms involved in the transfer across epithelial cells of plutonium (Pu) and americium (Am) as a function of their intrinsic properties (nature, physicochemical form) or their association with serum proteins, inorganic ligands or synthetic chelating agents. Both the contribution of the transcellular and paracellular routes to the transfer of these various forms were studied. Results show that uptake of Pu and Am by epithelial cells is not positively correlated with their transfer, which suggests that radionuclides transcytosis is a continuous process in comparison with the quick translocation of Pu/Am-small size complexes. Furthermore, reducing epithelial cells paracellular permeability with the glucocorticoid hormone Dexamethasone (DEX) resulted into a lower transfer of Pu citrate, and of both actinides in the presence of diethylene triamine pentaacetic acid (DTPA) and 3,4,3-LI(1,2-HOPO). Taken together, these results seem to indicate that a paracellular pathway may be responsible, at least partly, for the higher pulmonary absorption observed in vivo for actinides bound to low-molecular weight ligands such as citrate, DTPA or HOPO.