Lucey Catherine M, Pearson Brandon L, DeSantis Kathryn, Goldsmith Jeff, Halliday Alex N, Navas-Acien Ana, Schilling Kathrin, Basu Anirban
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, United States.
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York 10032, United States.
Environ Sci Technol. 2025 Jul 22;59(28):14279-14289. doi: 10.1021/acs.est.5c03403. Epub 2025 Jul 14.
Chronic low-level uranium (U) exposure through drinking water is a public health risk in the United States. Nearly two-thirds of community water systems, serving 320 million people, have detectable U levels, with 2% exceeding the EPA's maximum contaminant level of 30 μg/L. Ingested U accumulates in kidneys and is nephrotoxic at high levels. Uranium binds to proximal tubule cells, causing injury and interfering with kidney function. Epidemiological studies suggest that even low-level (<30 μg/L) of U exposure could damage kidneys. Current biomarkers, like urinary U levels, fail to indicate tissue-specific concentrations and metabolic interactions in kidneys. Fractionation of U/U may potentially serve as a biomarker for the metabolic interaction of U with organs. Our experiments with mice showed changes in U isotopic composition (U/U expressed as δU) in organs after administering 50 mg/L U via drinking water for 2, 7, and 14 days. We found U enrichment in kidneys and bones, the target organs, while urine was enriched in U. Our results provide evidence of isotopic fractionation resulting from U accumulation in kidneys. Urinary U isotopic composition may, thus, provide a sensitive, noninvasive measurement of renal U bioaccumulation that could aid early detection of nephrotoxicity and prevention of irreversible kidney damage.
通过饮用水长期低水平接触铀（U）是美国的一个公共卫生风险。为3.2亿人供水的社区供水系统中，近三分之二检测到铀含量，其中2%超过美国环境保护局（EPA）规定的30μg/L的最大污染物水平。摄入的铀在肾脏中蓄积，高剂量时具有肾毒性。铀与近端肾小管细胞结合，造成损伤并干扰肾功能。流行病学研究表明，即使低水平（<30μg/L）的铀接触也可能损害肾脏。目前的生物标志物，如尿铀水平，无法表明肾脏中的组织特异性浓度和代谢相互作用。铀同位素分馏可能作为铀与器官代谢相互作用的生物标志物。我们对小鼠进行的实验表明，通过饮用水给予50mg/L铀2天、7天和14天后，器官中的铀同位素组成（以δU表示的238U/235U）发生了变化。我们发现肾脏和骨骼（目标器官）中238U富集，而尿液中235U富集。我们的结果提供了肾脏中铀蓄积导致同位素分馏的证据。因此，尿铀同位素组成可能提供一种敏感、无创的肾脏铀生物蓄积测量方法，有助于早期发现肾毒性并预防不可逆的肾脏损伤。
