Differences in the Uptake of Transferrin Bound ²³⁹Pu and ⁵⁹Fe into Multicellular Spheroids of Hepatocytes from Adult Male Rats

Summary

Hepatocytes were cultured as monolayers and multicellular spheroids, respectively. The uptake of both transferrin-bound metals, iron and plutonium, differed significantly between these two culture systems. The uptake into the multicellular spheroids for plutonium was about 30 times greater, and for iron about 4 times greater, than in monolayer-cultured hepatocytes, which is not a consequence of proliferation and/or de-differentiation of the hepatocytes in the multicellular spheroid culture system. A comparison of the iron and plutonium uptake showed that plutonium was delivered to the cells to an 8-fold greater extent than iron if the hepatocytes were cultured as spheroids. Additionally, the binding of plutonium was not inhibited by preincubation of the spheroids with the iron-transferrin complex. Therefore, we propose that there are two different binding sites for iron and plutonium on hepatocyte membranes.