title: Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.
abstract: Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.
authors.affiliation: Research Center for Radiation Protection,Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Homma-Takeda
authors.affiliation: Graduate School of Science, Chiba University, Yayoi-cho, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kitahara
authors.affiliation: Research Center for Radiation Protection,Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.|Graduate School of Agriculture and life Sciences, University of Tokyo, Hongo, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Research Center for Radiation Protection,Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blyth
authors.affiliation: Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Suya
authors.affiliation: Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Japan Synchrotron Radiation Research Institute, Mikazuki, Hyogo, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Terada
authors.affiliation: Research Center for Radiation Protection,Research, Development and Support Center, National Institute of Radiological Sciences, Inage-ku Chiba, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D017208:Rats, Wistar; D066007:Toxicokinetics; D014501:Uranium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014501:Uranium
keywords: S3 segment; distribution; elemental imaging; kidney; localization; site-specific accumulation; uranium