Presentation Cellular localization of uranium in the proximal tubules and renal toxicity

Takeda, Shino  ,  Suzuki, Kyoko  ,  Kitahara, Keisuke  ,  Blyth, Benjamin  ,  Suya, Noriyoshi  ,  Konishi, Teruaki  ,  Terada, Yasuko  ,  Shimada, Yoshiya

The uses of uranium in the nuclear industry and military applications have led to growing public concern over its health effects. The kidney is known as the critical target for uranium toxicity. Uranium accumulates site-specifically into the S3 segments of the proximal tubule and causes tubular damage. However, the details of cellular localization of uranium, and the uranium levels in the micro region of the toxic target site during renal toxicity are not well understood. In this study, quantitative in situ determination of uranium concentration by high energy synchrotron radiation X-ray fluorescence analysis (SR-XRF) was performed for renal tissue sections, and subcellular dynamics and intracellular distribution of uranium in the S3 segments of the proximal tubule were examined in a rat model of uranium-induced acute renal toxicity.At one day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium/kg body weight, uranium concentration in the S3 segments of the proximal tubule was more than 50 μg/g, which was 7-fold higher than the mean renal uranium concentration. Uranium distributed into the epithelium of the S3 segments of the proximal tubule and highly concentrated uranium in micro-regions with 50-fold higher than the mean renal uranium concentration were found near the nuclei. The uranium concentration in the S3 segments were maintained at high levels compared to the mean renal uranium concentration, which had continued to decrease after administration. The areas of uranium concentration were found within necrotic proximal tubules at the late stage of tubular injury and in the epithelium of regenerating tubules during recovery. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segments of the proximal tubule, and retention of uranium in concentrated areas during recovery, are characteristics of uranium dynamics in the kidney. The involvement of the cellular localization of uranium in site-specific DNA damage will also be presented
15th International Congress of Radiation Research

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