Site-selective accumulation of uranium in the downstream of the proximal tubules and renal toxicity

抄録

The pollution caused by the military use of depleted uranium as well as the nuclear accident in Japan has raised increasing concern about its health effects. The kidney is known as the critical target for uranium toxicity, however its dynamics has not been clearly understood, may due to the difficulty of analytical methodology for the measurement of very low amount of radioactive uranium in tissues. In the present study, Wistar rats were exposed to uranium acetate and the distribution of uranium in the kidney were visualized by microbeam based elemental analysis performed by X-ray fluorescence spectrometry using high energy synchrotron radiation. Correlation between the accumulation of uranium and induction of apoptosis in the kidney was examined. As a result, accumulation of uranium were observed with the rats administrated with a dose of 0.5 mg/kg in the downstream of the proximal tubules (the S3 segment of the proximal tubules), where it caused renal apoptosis and lesions. However, the accumulations were not in the brush border membrane. During recovery, at day 15 after administration, uranium concentrated areas still contained uranium more than 180-fold of the mean uranium concentration in kidney. The involvement of the site-selective accumulation in age-dependent sensitivity to uranium in term of chemical toxicity and radiation effect will be presented.