Transmission electron microscopic and X-ray absorption fine structure spectroscopic investigation of U repartition and speciation after accumulation in renal cells

J Biol Inorg Chem. 2008 Jun;13(5):655-62. doi: 10.1007/s00775-008-0350-2. Epub 2008 Feb 14.

Abstract

After environmental contamination, U accumulates in the kidneys and in bones, where it causes visible damage. Recent in vitro data prove that the occurrence of citrate increases U bioavailability without changing its speciation. Two hypotheses can explain the role of citrate: it either modifies the U intracellular metabolization pathway, or it acts on the transport of U through cell membrane. To understand which mechanisms lead to increased bioavailability, we studied the speciation of U after accumulation in NRK-52E kidney cells. U speciation was first identified in various exposure media, containing citrate or not, in which U was supplied as U carbonate. The influence of serum proteins was analyzed in order to detect the formation of macromolecular complexes of U. Transmission electron microscopy (TEM) was employed to follow the evolution of the U species distribution among precipitated and soluble forms. Finally, extended X-ray absorption fine structure spectroscopy (EXAFS) enabled the precipitates observed to be identified as U-phosphate. It also demonstrated that the intracellular soluble form of U is U carbonate. These results suggest that citrate does not change U metabolization but rather plays a role in the intracellular accumulation pathway. U speciation inside cells was directly and clearly identified for the first time. These results elucidate the role of U speciation in terms of its bioavailability and consequent health effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Kidney / metabolism*
  • Kidney / ultrastructure
  • LLC-PK1 Cells
  • Microscopy, Electron, Transmission*
  • Rats
  • Spectrum Analysis
  • Swine
  • Uranium Compounds / metabolism*
  • Uranium Compounds / pharmacokinetics
  • X-Rays

Substances

  • Uranium Compounds