Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.
References
[1]
Wesch, H; Wiethege, T; Spiethoff, A; Wegener, K; Muller, K-M; Mehlhorn, J. German uranium miner study-historical background and available histopathological material. Radiat. Res？1999, 152, S48–S51, doi:10.2307/3580113. 10564936
[2]
Briner, W. The evolution of depleted uranium as an environmental risk factor, lessons from other metals. Int. J. Environ. Res. Public Health？2006, 3, 129–135, doi:10.3390/ijerph2006030016. 16823086
[3]
Taylor, DM; Taylor, SK. Environmental uranium and human health. Rev. Environ. Health？1997, 12, 147–57. 9406286
[4]
Oliver, IW; Graham, MC; MacKenzie, AB; Ellam, RM; Farmer, JG. Depleted uranium mobility across a weapons testing site: isotopic investigation of porewater, earthworms, and soils. Environ. Sci. Technol？2008, 42, 9158–9164, doi:10.1021/es8013634. 19174886
[5]
Salbu, B; Janssens, K; Lind, OC; Proost, K; Danesi, PR. Oxidation states of uranium in DU particles from Kosovo. J. Environ. Radioact？2003, 64, 167–173, doi:10.1016/S0265-931X(02)00047-4. 12500803
[6]
Leggett, RW. Biokinetics of uranium in the human body. In Depleted Uranium, Properties, Uses, and Health Consequences; Miller, A, Ed.; CRC Press: New York, NY, USA, 2007; pp. 163–182.
[7]
Durakovic, A; Horan, P; Dietz, LA; Zimmerman, I. Estimate of the time zero lung burden of depleted uranium in Persian Gulf War veterans by the 24-hour urinary excretion and exponential decay analysis. Mil. Med？2003, 168, 600–605. 12943033
[8]
Zhu, G; Tan, M; Li, Y; Xiang, X; Hu, H; Zhao, S. Accumulation and distribution of uranium in rats after implanation with depleted uranium fragments. J. Radiat. Res. (Tokyo)？2009, 50, 183–192, doi:10.1269/jrr.08104.
[9]
Zhu, G; Xiang, X; Chen, X; Wang, L; Hu, H; Weng, S. Renal dysfunction induced by long-term exposure to depleted uranium in rats. Arch. Toxicol？2009, 83, 37–46, doi:10.1007/s00204-008-0326-6. 18594794
[10]
Berradi, H; Bertho, JM; Dudoignon, N; Mazur, A; Grandcolas, L; Baudelin, C; Grison, S; Voisin, P; Gourmelon, P; Dublineau, I. Renal anemia induced by chronic ingestion of depleted uranium in rats. Toxicol. Sci？2008, 103, 397–408, doi:10.1093/toxsci/kfn052. 18375546
[11]
Barber, DS; Hancock, SK; McNally, AM; Hinckley, J; Binder, E; Zimmerman, K; Ehrich, MF; Jortner, BS. Neurological effects of acute uranium exposure with and without stress. Neurotoxicology？2007, 28, 1110–1119, doi:10.1016/j.neuro.2007.05.014. 17669499
[12]
Monleau, M; Bussy, C; Lestaevel, P; Houpert, P; Paquet, F; Chazel, V. Bioaccumulation and behavioral effects of depleted uranium in rats exposed to repeated inhalations. Neurosci. Lett？2005, 390, 31–36, doi:10.1016/j.neulet.2005.07.051. 16115730
[13]
Domingo, JL; Llobet, JM; Tomas, JM; Corbella, J. Acute toxicity of uranium in rats and mice. Bull. Environ. Contam. Toxicol？1987, 39, 168–174, doi:10.1007/BF01691806. 3607315
[14]
Lin, RH; Fu, WM; Lin-Shiau, SY. Presynaptic action of uranyl nitrate on the phrenic nervediaphragm preparation of the mouse. Neuropharmacology？1988, 27, 857–863, doi:10.1016/0028-3908(88)90103-7. 3216965
[15]
Raymond-Whish, S; Mayer, LP; O’Neal, T; Martinez, A; Sellers, MA; Christian, PJ; Marion, SL; Begay, C; Propper, CR; Hoyer, PB; Dyer, CA. Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor–dependent responses in female mice. Environ. Health Perspect？2007, 115, 1711–1716, doi:10.1289/ehp.9910. 18087588
[16]
Tissandié, E; Guéguen, Y; Lobaccaro, JM; Grandcolas, L; Aigueperse, J; Gourmelon, P; Souidi, M. Enriched uranium affects the expression of vitamin D receptor and retinoid X receptor in rat kidney. J. Steroid Biochem. Mol. Biol？2008, 110, 263–268, doi:10.1016/j.jsbmb.2007.11.002. 18502116
[17]
Bussy, C; Lestaevel, P; Dhieux, B; Amourette, C; Paquet, F; Gourmelon, P; Houpert, P. Chronic ingestion of uranyl nitrate perturbs acetylcholinesterase activity and monoamine metabolism in male rat brain. Neurotoxicology？2006, 27, 245–252, doi:10.1016/j.neuro.2005.11.003. 16325913
[18]
Briner, W. Effects of depleted uranium on mouse midbrain catecholamines and related behavior. Int J Toxicol？2009, 7.
[19]
Dublineau, I; Grandcolas, L; Grison, S; Baudelin, C; Paquet, F; Voisin, P; Aigueperse, J; Gourmelon, P. Modifications of inflammatory pathways in rat intestine following chronic ingestion of depleted uranium. Toxicol. Sci？2007, 98, 458–468, doi:10.1093/toxsci/kfm132. 17566059
[20]
Bellés, M; Linares, V; Luisa-Albina, M; Sirvent, J; Sánchez, DJ; Domingo, JL. Melatonin reduces uranium-induced nephrotoxicity in rats. J. Pineal. Res？2007, 43, 87–95, doi:10.1111/j.1600-079X.2007.00447.x. 17614840
[21]
Ghosh, S; Kumar, A; Pandey, BN; Mishra, KP. Acute exposure of uranyl nitrate causes lipid peroxidation and histopathological damage in brain and bone of Wistar rat. J. Environ. Pathol. Toxicol. Oncol？2007, 26, 255–261, doi:10.1615/JEnvironPatholToxicolOncol.v26.i4.20. 18197823
[22]
Linares, V; Sánchez, DJ; Bellés, M; Albina, L; Gómez, M; Domingo, JL. Pro-oxidant effects in the brain of rats concurrently exposed to uranium and stress. Toxicology？2007, 236, 82–91, doi:10.1016/j.tox.2007.04.001. 17493736
[23]
Briner, W; Abboud, B. Behavior of juvenile mice chronically exposed to depleted uranium. In Proceedings of the 7th Symposium Metal Ions in Biology and Medicine, 7th ed; Khassanova, L, Collery, Ph, Maymard, I, Khassanova, Z, Etienne, JC, Eds.; John Libby Eurotext: Paris, France, 2002; pp. 353–356.
[24]
Briner, W; Davis, D. Lipid peroxidation and behavior are correlated in depleted uranium exposed mice. In Proceedings of the 7th Symposium Metal Ions in Biology and Medicine, 7th ed; Khassanova, L, Collery, Ph, Maymard, I, Khassanova, Z, Etienne, JC, Eds.; John Libby Eurotext: Paris, France, 2002; pp. 59–63.
[25]
Briner, W; Murray, J. Effects of short-term and long-term depleted uranium exposure on open-field behavior and brain lipid peroxidation in rats. Neuotoxicol. Teratol？2005, 27, 135–144, doi:10.1016/j.ntt.2004.09.001.
[26]
Racine, R; Gueguen, Y; Gourmelo, P; Veyssiere, G; Souidi, M. Modifications of the expression of genes involved in cerebral cholesterol metabolism in the rat following chronic ingestion of depleted uranium. J. Mol. Neurosci？2008, 38, 159–165. 18792811
[27]
Lestaevel, P; Romero, E; Dhieux, B; Ben Soussan, H; Berradi, H; Dublineau, I; Voisin, P; Gourmelo, P. Different pattern of brain pro-antioxidant activity between depleted and enriched uranium in chronically exposed rats. Toxicology？2009, 258, 1–9, doi:10.1016/j.tox.2008.12.021. 19154773
[28]
Pellmar, TC; Keyser, DO; Emery, C; Hogan, JB. Electrophysiological changes in hippocampal slices isolated from rats embedded with depleted uranium fragments. Neurotoxicology？1999, 20, 785–792. 10591514
[29]
Lestaevel, P; Bussy, C; Paquet, F; Dhieux, B; Clarencon, D; Houpert, P; Gourmelon, P. Changes in sleep-wake cycle after chronic exposure to uranium in rats. Neurotoxol. Teratol？2005, 27, 835–840, doi:10.1016/j.ntt.2005.07.005.
[30]
Lestaevel, P; Houpert, P; Bussy, C; Dhieux, B; Gourmelon, P; Paquet, F. The brain is a target organ after acute exposure to depleted uranium. Toxicology？2005, 1, 219–226.
[31]
Briner, W. Neurotoxicology of depleted uranium in adult and developing rodents. In Depleted Uranium, Properties, Uses, and Health Consequences; Miller, A, Ed.; CRC Press: New York, NY, USA, 2007; pp. 67–74.
[32]
Houpert, P; Lestaevel, P; Bussy, C; Paquet, F; Gourmelo, P. Enriched but not depleted uranium affects central nervous system in long-term exposed rat. Neurotoxicology？2005, 26, 1015–1020, doi:10.1016/j.neuro.2005.05.005. 15996736
[33]
Kathren, RL; Burklin, RK. Acute chemical toxicity of uranium. Health Phys？2008, 94, 170–179, doi:10.1097/01.HP.0000288043.94908.1f. 18188051
Fukuda, S; Ikeda, M; Nakamura, M; Yan, X; Xie, Y. Efficacy of oral and intraperitoneal administration of CBMIDA for removing uranium in rats after parenteral injections of depleted uranium Radiat Prot. Dosimetry？2009, 133, 12–19.
[36]
Hinden, R; Brugge, D; Panikkar, B. Teratogenicity of deplted uranium aerosols: A review from an epidemiological perspective. Env. Health: Global Access？2005, 4, 17.
[37]
Briner, W; Byrd, K. Effects of Depleted Uranium on Development of the Mouse. In Proceedings of the 6th International Symposium on Metal Ions in Biology and Medicine, 6th ed; Centeno, J, Collery, P, Vernet, G, Finkelman, R, Gibb, H, Etienne, J-C, Eds.; John Libby Eurotext: Paris, France, 2000; Volume 6, pp. 459–461.
[38]
McDiarmid, MA; Engelhardt, SM; Oliver, M. Urinary uranium concentrations in an enlarged Gulf War veteran cohort. Health Phys？2001, 80, 270–273, doi:10.1097/00004032-200103000-00010. 11219540
[39]
McDiarmid, MA; Keogh, JP; Hooper, FJ; McPhaul, K; Squibb, K; Kane, R; DiPino, R; Kabat, M; Kaup, B; Anderson, L; Hoover, D; Brown, L; Hamilton, M; Jacobson-Kram, D; Burrows, B; Walsh, M. Health effects of depleted uranium on exposed Gulf War veterans. Environ. Res？2000, 82, 168–180, doi:10.1006/enrs.1999.4012. 10662531
[40]
Durakovic, A. Medical effects of internal contamination with uranium. Croatian Med. J？1999, 40, 49–66.
[41]
Papathanasiou, K; Gianoulis, C; Tolikas, A; Dovas, D; Koutsos, J; Fragkedakis, N; Papathanasiou, N. Effect of depleted uranium weapons used in the Balkan war on the incidence of cervical intraepithelial neoplasia (CIN) and invasive cancer of the cervix in Greece. Clin. Exp. Obstet. Gynecol？2005, 32, 58–60. 15864941
[42]
Obralic, N; Gavrankapetanovic, F; Dizdarevic, Z; Duric, O; Sisic, F; Selak, I; Balta, S; Nakas, B. The number of malignant neoplasm in Sarajevo region during the period 1998–2002. Med. Arch？2004, 58, 275–278.
[43]
Ibrulj, S; Krunic-Haveric, A; Haveric, S; Pojskic, N; Hadziselimovic, R. Micronuclei occurrence in population exposed to depleted uranium and control human group in correlation with sex, age and smoking habit. Med. Arch？2004, 58, 335–338.
[44]
Schroder, H; Heimers, A; Frentzel-Beyme, R; Schott, A; Hoffmann, W. Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans. Radiat. Prot. Dosimetry？2003, 103, 211–219, doi:10.1093/oxfordjournals.rpd.a006135. 12678382
[45]
Milacic, S. Health investigations of depleted-uranium clean-up workers. Med. Lav？2008, 99, 366–70. 18828536
[46]
Milacic, S; Simic, J. Identification of health risks in workers staying and working on the terrains contaminated with depleted uranium. J. Radiat. Res. (Tokyo)？2009, 50, 213–222, doi:10.1269/jrr.08131.
[47]
Miller, AC; Brooks, K; Smith, J; Page, N. Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2). Mol. Cell Biochem？2004, 255, 247–256, doi:10.1023/B:MCBI.0000007280.72510.96. 14971665
[48]
Yazzie, M; Gamble, SL; Civitello, ER; Stearns, DM. Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (vitamin C). Chem. Res. Toxicol？2003, 16, 524–530, doi:10.1021/tx025685q. 12703969
[49]
Yang, ZH; Fan, BX; Lu, Y; Cao, ZS; Yu, S; Fan, FY; Zhu, MX. Malignant transformation of human bronchial epithelial cell (BEAS-2B) induced by depleted uranium. Ai Zheng？2002, 21, 944–948. 12508538
[50]
Miller, AC; Brooks, K; Stewart, M; Anderson, B; Shi, L; McClain, D; Page, N. Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation. J. Environ. Radioact？2003, 64, 247–259, doi:10.1016/S0265-931X(02)00053-X. 12500809
[51]
Miller, AC; Xu, J; Stewart, M; Brooks, K; Hodge, S; Shi, L; Page, N; McClain, D. Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints. Radiat. Prot. Dosimetry？2002, 99, 275–278, doi:10.1093/oxfordjournals.rpd.a006783. 12194305
[52]
Miller, AC; Xu, J; Stewart, M; McClain, D. Suppression of depleted uranium-induced neoplastic transformation of human cells by the phenyl fatty acid, phenyl acetate: chemoprevention by targeting the p21RAS protein pathway. Radiat. Res？2001, 155, 163–170, doi:10.1667/0033-7587(2001)155[0163:SODUIN]2.0.CO;2. 11121229
[53]
Miller, AC; Blakely, WF; Livengood, D; Whittaker, T; Xu, J; Ejnik, JW; Hamilton, MM; Parlette, E; John, TS; Gerstenberg, HM; Hsu, H. Transformation of human osteoblast cells to the tumorigenic phenotype by depleted uranium-uranyl chloride. Environ. Health Perspect？1998, 106, 465–471, doi:10.1289/ehp.98106465. 9681973
Hahn, FF; Guilmette, RA; Hoover, MD. Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats. Environ. Health Perspect？2002, 110, 51–59. 11781165
[56]
Miller, AC; Fuciarelli, AF; Jackson, WE; Ejnik, EJ; Emond, C; Strocko, S; Hogan, J; Page, N; Pellmar, T. Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets. Mutagenesis？1998, 13, 643–648, doi:10.1093/mutage/13.6.643. 9862198
[57]
Miller, AC; Stewart, M; Rivas, R. DNA methylation during depleted uranium-induced leukemia. Biochimie？2009, 91, 1328–1330, doi:10.1016/j.biochi.2009.03.010. 19324073
[58]
Feugier, A; Frelon, S; Gourmelon, P; Claraz, M. Alteration of mouse oocyte quality after a subchronic exposure to depleted uranium. Reprod. Toxicol？2008, 26, 273–277, doi:10.1016/j.reprotox.2008.09.011. 18926898
[59]
Grignard, E; Gueguen, Y; Grison, S; Lobaccaro, JM; Gourmelon, P; Souidi, M. Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism of the rat. Int. J. Toxicol？2008, 27, 323–328, doi:10.1080/10915810802367057. 18821396
[60]
Parrish, RP; Horstwood, M; Arnason, JG; Chenery, S; Brewer, T; Lloyd, NS; Carpenter, DO. Depleted uranium contamination by inhalation exposure and its detection after ~20 years: Implication for human health assessment. Sci. Tot. Env？2008, 390, 58–68, doi:10.1016/j.scitotenv.2007.09.044.
