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Depleted Uranium Papers & Articles

DEPLETED URANIUM: ALL THE QUESTIONS ABOUT DU AND GULF WAR SYNDROME ARE NOT YET ANSWERED
Rosalie Bertell
Respond to Depleted Uranium/Low Level Radioactive Materials (DULLRAM) Hazards U.S. Army Soldiers' Handbook

Clean up DU Sites Including Hawai‘i Press Release by Dr. Doug Rokke

Army Environmental Policy Institue Paper Re Above Policy by Dr. Doug Rokke

Weapons of Self-Destruction Vanity Fair Article by David Rose

"... to measure the effect of D.U. as a whole-body radiation dose is meaningless, Asaf Durakovic says, because the dose from D.U. is intensely concentrated in the cells around a mote of dust. The alpha particles D.U. emits-high-energy clumps of protons and neutrons-are harmless outside the body, because they cannot pass through skin. Inside tissue, however, they wreak a havoc analogous to that of a penetrating shell against an enemy tank, bombarding cell nuclei, breaking chains of DNA, damaging fragile genes.

... the cells around a D.U. particle 2.5 microns in diameter will receive a maximum annual radiation dose of 16 rads. If every pocket of tissue in the body were to absorb that amount of radiation, the total level would reach seven trillion rads-millions of times the lethal dosage. In the potentially thousands of hot spots inside the lungs of a person exposed to D.U. dust, the same cells will be irradiated again and again, until their ability to repair themselves is lost."

"Within months of the war's end, thousands of Gulf War veterans began suffering from odd, nameless maladies, including hair loss, bleeding gums, memory loss, joint pain, incontinence. and disabling fatigue. In 1992, Sen. Ron Wyden (D-Ore.) asked the General Accounting Office, an independent research arm of Congress, to study American tanks that had been hit by DU rounds during the war. GAO investigators learned that most soldiers had never been informed by their superiors about the hazards of DU. The GAO's findings were summarized in the title of its report issued a year later: "Army Not Adequately Prepared to Deal with Depleted Uranium Contamination".

Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium. 
Mol Cell Biochem. 2005 Nov;279(1-2):97-104.
Miller AC, Bonait-Pellie C, Merlot RF, Michel J, Stewart M, Lison PD.
Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research, Institute, Bethesda, Maryland, USA.

Depleted uranium (DU) is a dense heavy metal used in military applications. During military conflicts, US military personnel have been wounded by DU shrapnel. The health effects of embedded DU are unknown. Published data from our laboratory demonstrated that DU exposure in vitro can transform immortalized human osteoblast cells (HOS) to the tumorigenic phenotype. Results from our laboratory have also shown that DU is genotoxic and mutagenic in cultured human cells. Internalized DU could be a carcinogenic risk and concurrent alpha particle and heavy metal toxic effects complicate this potential risk. Anecdotal reports have suggested that DU can cause leukemia. To better assess this risk, we have developed an in vivo leukemogenesis model. This model involves using murine hematopoietic cells (FDC-P1) that are dependent on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin 3 (IL-3) and injected into mice to produce myeloid leukemia. Although immortalized, these cells are not tumorigenic on subcutaneous inoculation in mice. Intravenous injection of FDC-P1 cells into DU-implanted DBA/2 mice was followed by the development of leukemias in 76% of all mice implanted with DU pellets. In contrast, only 12% of control mice developed leukemia. Karyotypic analysis confirmed that the leukemias originated from FDC-P1 cells. The growth properties of leukemic cells from bone marrow, spleen, and lymph node were assessed and indicate that the FDC-P1 cells had become transformed in vivo. The kidney, spleen, bone marrow, muscle, and urine showed significant elevations in tissue uranium levels prior to induction of leukemia. These results demonstrated that a DU altered in vivo environment may be involved in the pathogenesis of DU induced leukemia in an animal model.

Proteomic analysis of the response of human lung cells to uranium. 
Proteomics. 2005 Nov;5(17):4568-80.
Malard V, Prat O, Darrouzet E, Berenguer F, Sage N, Quemeneur E.
Service de Biochimie post-genomique et Toxicologie Nucleaire, DSV/DIEP, CEA VALRHO, Bagnols-sur-Ceze, France. veronique.malard@cea.fr

The industrial use of uranium and particularly of depleted uranium, has pinpointed the need to review its chemical impact on human health. A proteomic approach was used to evaluate the response of a human lung cell line (A549) to uranium. We established the first 2-D reference map of the A549 cell line, identifying 87 spots corresponding to 81 major proteins. Uranium treatment triggered differential expression of 18 spots, of which 14 corresponded to fragments of cytokeratin 8 (CK8) and cytokeratin (CK18) and 1 to peroxiredoxin 1. We probed several hypotheses regarding CK cleavage, and observed that it did not result from caspase or calpain activity. Furthermore, we showed that the fragments are recognised by an anti-ubiquitin antibody (KM691). These results suggest a regulatory pathway involving CK ubiquitinylation or dysfunction in the proteasome-ubiquitin system in response to uranium exposure in human lung cells.


Short-term hepatic effects of depleted uranium on xenobiotic and bile acid metabolizing cytochrome P450 enzymes in the rat.   Arch Toxicol. 2005 Oct 18;:1-9 [Epub ahead of print]
Gueguen Y, Souidi M, Baudelin C, Dudoignon N, Grison S, Dublineau I, Marquette C, Voisin P, Gourmelon P, Aigueperse J.
Institut de Radioprotection et de Surete Nucleaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidemiologie. IRSN, B.P. No. 17, F 92262, Fontenay-aux-Roses Cedex, France, yann.gueguen@irsn.fr.

The toxicity of uranium has been demonstrated in different organs, including the kidneys, skeleton, central nervous system, and liver. However, few works have investigated the biological effects of uranium contamination on important metabolic function in the liver. In vivo studies were conducted to evaluate its effects on cytochrome P450 (CYP) enzymes involved in the metabolism of cholesterol and xenobiotics in the rat liver. The effects of depleted uranium (DU) contamination on Sprague-Dawley were measured at 1 and 3 days after exposure. Biochemical indicators characterizing liver and kidney functions were measured in the plasma. The DU affected bile acid CYP activity: 7alpha-hydroxycholesterol plasma level decreased by 52% at day 3 whereas microsomal CYP7A1 activity in the liver did not change significantly and mitochondrial CYP27A1 activity quintupled at day 1. Gene expression of the nuclear receptors related to lipid metabolism (FXR and LXR) also changed, while PPARalpha mRNA levels did not. The increased mRNA levels of the xenobiotic-metabolizing CYP3A enzyme at day 3 may be caused by feedback up-regulation due to the decreased CYP3A activity at day 1. CAR mRNA levels, which tripled on day 1, may be involved in this up-regulation, while mRNA levels of PXR did not change. These results indicate that high levels of depleted uranium, acting through modulation of the CYP enzymes and some of their nuclear receptors, affect the hepatic metabolism of bile acids and xenobiotics.

Genotoxic and Inflammatory Effects of Depleted Uranium Particles Inhaled by Rats. 
Toxicol Sci. 2006 Jan;89(1):287-295. Epub 2005 Oct 12.
Monleau M, De Meo M, Paquet F, Chazel V, Dumenil G, Donnadieu-Claraz M.
IRSN/DRPH/SRBE, Laboratoire de Radiotoxicologie Experimentale, BP 166, 26702 Pierrelatte Cedex, France; Laboratoire de Biogenotoxicologie et mutagenese environnementale, Universite de la Mediterranee, Faculte de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille, France Laboratoire de Microbiologie, Universite de la Mediterranee, Faculte de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille, France.

Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation.


Inducible nitric oxide synthase gene expression in the testis of rats instilled with depleted uranium particles.
Zhonghua Nan Ke Xue. 2005 Sep;11(9):655-7.
LJSh.WJ@eyou.com   [Article in Chinese]
Li JS, Zhang H, Wang HR, Yang F, Chne J.
Institute of Military Preventive Medicine, Medical College of the Chinese People's Armed Police Forces, Tianjin 300162, China. LJSh.WJ@eyou.com

OBJECTIVE: To explore genital toxicity of depleted uranium (DU) by studying the changes of inducible nitric oxide synthase (iNOS) in the testis of rats instilled with DU particles. METHODS: Wistar rats were exposed to DU by means of different dosages of DU particles intratracheal instillation. The samples of the testis were collected 3 months later, and iNOS mRNA was determined by reverse-transcription PCR (RT-PCR). Semiquantitative analysis of the RT-PCR products was made with a transilluminator. RESULTS: iNOS mRNA was not observed in the control group. Compared with the control, there were significant increases of OD in the PCR products of all the DU groups (P < 0. 05 ); OD rose gradually from the DU 1 mg group to the DU 3 mg group, peaked in the latter, and subsided significantly in the DU 5 mg group (P < 0.05). CONCLUSION: Intratracheal instilled DU particles play a key role in iNOS mRNA expression of the rat testis. The iNOS mRNA expression will weaken when the DU dosage reaches a certain level, which may attribute to the complex of DU's chemical toxicity and radiation effects.


Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells. 
Mutagenesis. 2005 Nov;20(6):417-23. Epub 2005 Sep 29.
Stearns DM, Yazzie M, Bradley AS, Coryell VH, Shelley JT, Ashby A, Asplund CS, Lantz RC.
Department of Chemistry and Biochemistry, Northern Arizona University, PO Box 5698, Flagstaff, AZ 86011-5698 and Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA.

Questions about possible adverse health effects from exposures to uranium have arisen as a result of uranium mining, residual mine tailings and use of depleted uranium in the military. The purpose of the current study was to measure the toxicity of depleted uranium as uranyl acetate (UA) in mammalian cells. The activity of UA in the parental CHO AA8 line was compared with that in the XRCC1-deficient CHO EM9 line. Cytotoxicity was measured by clonogenic survival. A dose of 200 microM UA over 24 h produced 3.1-fold greater cell death in the CHO EM9 than the CHO AA8 line, and a dose of 300 microM was 1.7-fold more cytotoxic. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. A dose of 200 microM UA produced approximately 5-fold higher averaged induced mutant frequency in the CHO EM9 line relative to the CHO AA8 line. The generation of DNA strand breaks was measured by the alkaline comet assay at 40 min and 24 h exposures. DNA strand breaks were detected in both lines; however a dose response may have been masked by U-DNA adducts or crosslinks. Uranium-DNA adducts were measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 24 and 48 h exposures. A maximum adduct level of 8 U atoms/10(3) DNA-P for the 300 microM dose was found in the EM9 line after 48 h. This is the first report of the formation of uranium-DNA adducts and mutations in mammalian cells after direct exposure to a depleted uranium compound. Data suggest that uranium could be chemically genotoxic and mutagenic through the formation of strand breaks and covalent U-DNA adducts. Thus the health risks for uranium exposure could go beyond those for radiation exposure.



Micronuclei frequencies in peripheral blood lymphocytes of individuals exposed to depleted uranium.
Arh Hig Rada Toksikol. 2005 Sep;56(3):227-32.
Krunic A, Haveric S, Ibrulj S.
Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia. and Herzegovina. anja.krunic@www.ingeb.ba

One of the negative environmental impacts of the last armed conflict in Bosnia and Herzegovina was the use of radioactive ammunition containing depleted uranium. The United Nations Environment Programme measurements detected higher radioactivity at several examined sites in Bosnia and Herzegovina. One of those places is in the area of Hadzici, close to Sarajevo. This research included an evaluation of genetic load in human lymphocytes due to exposure to depleted uranium. The study included individuals who were located in the area of Hadzici and who were directly exposed to depleted uranium. The control blood samples were taken from individuals who lived in West Herzegovina which is considered environmentally uncontaminated. The results of the micronucleus cytochalasin-B test in peripheral blood lymphocytes showed increased micronuclei frequencies in the exposed group.



Measurement of the 234U/238U ratio by MC-ICPMS in drinking water, hair, nails, and urine as an indicator of uranium exposure source.
Health Phys. 2005 Oct;89(4):315-21.
Karpas Z, Lorber A, Sela H, Paz-Tal O, Hagag Y, Kurttio P, Salonen L.
Nuclear Research Center, Negev, Beer-Sheva, Israel. karpas4@netvision.net.il

The isotopic ratio (234)U/(238)U in drinking water and in hair, toenail, and urine samples from 45 individuals who consumed 0.2-2775 microg d(-1) of uranium in their drinking water was determined using a multi-collector inductively coupled plasma mass spectrometer (MC-ICPMS). The U/U atom ratio in the water samples varied from 51 x 10(-6) to 252 x 10(-6) whereas in secular equilibrium (i.e., unity activity ratio) the ratio is 54.9 x 10(-6). The correlation of the (234)U/(238)U ratio between hair and nail samples was 0.98, and between hair and nails and urine the ratio was 0.91 and 0.89, respectively. The correlation of the ratio between water and the hair or nails was 0.97 but only 0.72 for water and urine, possibly due to spectral interferences. These results conclusively demonstrated that the uranium found in the bioassays can be traced to the drinking water, thus providing a direct link to the source of exposure. Hair may serve as an excellent indicator of occupational or environmental exposure to uranium and provide information regarding its source. Bioassay of hair is attractive as it is an effective bio-concentrator, samples can be easily stored, the concentration reflects an integrated value, and, finally, the measurement of the (234)U/(238)U isotopic ratio in digested hair samples by MC-ICPMS is feasible and highly informative. Hair bioassay can also be used to assess exposure to depleted uranium long after the subjects have left the area suspected of contamination.