Toxicity studies on depleted uranium in primary rat cortical neurons and in caenorhabditis elegans: What have we learned?

Journal of Toxicology and Environmental Health - Part B: Critical Reviews

Volumn 12, Issue 7, 2009, Pages 525-539

  Aschner, Michael ^a,b   Jiang, George C T ^a  

^a Department of Pediatrics ^*  (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOPROSTANE; METALLOTHIONEIN; PHOSPHATE; THIOL; URANIUM; ISOPROSTANE DERIVATIVE;

BRAIN CELL; CAENORHABDITIS ELEGANS; COGNITION; ELECTROPHYSIOLOGY; HIGH ENERGY PHOSPHATE; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; RADIOACTIVITY; REVIEW; SENSORIMOTOR FUNCTION; TOXICITY TESTING; VETERAN; ANIMAL; BRAIN CORTEX; DRUG EFFECT; ENVIRONMENTAL EXPOSURE; METABOLISM; NERVE CELL; PHYSIOLOGY; RAT;

CAENORHABDITIS ELEGANS; RATTUS; RODENTIA;

ANIMALS; CAENORHABDITIS ELEGANS; CEREBRAL CORTEX; ENVIRONMENTAL EXPOSURE; ISOPROSTANES; METALLOTHIONEIN; NEURONS; PHOSPHATES; RATS; URANIUM;

EID: 77949534743     PISSN: 10937404     EISSN: 15216950     Source Type: Journal    
DOI: 10.1080/10937400903358942     Document Type: Review

References (128)

1. Abou-Donia, M. B., Dechkovskaia, A. M., Goldstein, L. B., Shah, D. U., Bullman, S. L., and Khan, W. A. 2002. Uranyl acetate-induced sensorimotor deficit and increased nitric oxide generation in the central nervous system in rats. Pharmacol. Biochem. Behav. 72:881-890.
2. Abu-Qare, A. W., and Abou-Donia, M. B. 2001. Determination of depleted uranium, pyridostigmine bromide and its metabolite in plasma and urine following combined administration in rats. J. Pharm. Biomed. Anal. 26:281-289.
3. Abu-Qare A. W., and Abou-Donia, M. B. 2002. Depleted uranium-The growing concern. J. Appl. Toxicol. 22:149-152.
4. Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D. J. 1997. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res. 25:3389-3402.
5. Anckar, J., and Sistonen, L. 2007. Heat shock factor 1 as a coordinator of stress and developmental pathways. Adv. Exp. Med. Biol. 594:78-88.
6. Andrews, G. K. 2000. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem. Pharmacol. 59:95-104.
7. Aravindakumar, C. T., Ceulemans, J., and De Ley, M. 1999. Nitric oxide induces Zn2+ release from metallothionein by destroying zinc-sulphur clusters without concomitant formation of S-nitrosothiol. Biochem. J. 34:253-258.
8. Arfsten, D. P., Bekkedal, M., Wilfong, E. R., Rossi, J. 3rd, Grasman, K. A., Healey, L. B., Rutkiewicz, J. M., Johnson, E. W., Thitoff, A. R., Jung, A. E., Lohrke, S. R., Schaeffer, D. J., and Still, K. R. 2005. Study of the reproductive effects in rats surgically implanted with depleted uranium for up to 90 days. J. Toxicol. Environ. Health A 68:967-997.
9. Arfsten, D. P., Still, K. R., and Ritchie, G. D. 2001. A review of the effects of uranium and depleted uranium exposure on reproduction and fetal development. Toxicol. Ind. Health 17:180-191.
10. Armitage, I. M., Otvos, J. D., Briggs, R. W., and Boulanger, Y. 1982. Structure elucidation of the metal-binding sites in metallothionein by 113Cd NMR. Fed. Proc. 41:2974-2980.
11. 7]metallothionein-2a in aqueous solution determined by nuclear magnetic resonance. J. Mol. Biol. 201:637-657.
12. Barber, D. S., Ehrich, M. F., and Jortner, B. S. 2005. The effect of stress on the temporal and regional distribution of uranium in rat brain after acute uranyl acetate exposure. J. Toxicol. Environ. Health A 68:99-111.
13. Belles, M., Albina, M. L., Linares, V., Gomez, M., Sanchez, D. J., and Domingo, J. L. 2005. Combined action of uranium and stress in the rat. I. Behavioral effects. Toxicol. Lett. 158:176-185.
14. Bleise, A., Danesi, P. R., and Burkart, W. 2003. Properties, use and health effects of depleted uranium (DU): A general overview. J. Environ. Radioact. 64:93-112.
15. Briggs, R. W., and Armitage, I. M. 1982. Evidence for site-selective metal binding in calf liver metallothionein. J. Biol. Chem. 257:1259-1262.
16. Briner, W., and Murray, J. 2005. Effects of short-term and long-term depleted uranium exposure on open-field behavior and brain lipid oxidation in rats. Neurotoxicol. Teratol. 27:135-144.
17. Bruinsma, J. J., Jirakulaporn, T., Muslin, A. J., and Kornfeld, K. 2002. Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev. Cell 2:567-578.
18. Brun, A., Abdulla, M., Ihse, I., and Samuelsson, B. 1976. Uptake and localization of mercury in the brain of rats after prolonged oral feeding with mercuric chloride. Histochemistry 47:23-29.
19. Carriere, M., Avoscan, L., Collins, R., Carrot, F., Khodja, H., Ansoborlo, E., and Gouget, B. 2004. Influence of uranium speciation on normal rat kidney (NRK-52E) proximal cell cytotoxicity. Chem. Res. Toxicol. 17:446-452.
20. Church, H. J., Day, J. P., Braithwaite, R. A., and Brown, S. S. 1993. Binding of lead to a metallothionein-like protein in human erythrocytes. J. Inorg. Biochem. 49:55-68.
21. Cobbett, C., and Goldsbrough, P. 2002. Phytochelatins and metallothioneins: Roles in heavy metal detoxification and homeostasis. Annu. Rev. Plant Biol. 53:159-182.
22. Cobbett, C. S. 2000. Phytochelatins and their roles in heavy metal detoxification. Plant Physiol. 123:825-832.
23. Coryell, V. H., and Stearns, D. M. 2006. Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells by uranyl acetate, by hydrogen peroxide, and spontaneously. Mol. Carcinogen. 45:60-72.
24. Craft, E., Abu-Qare, A., Flaherty, M., Garofolo, M., Rincavage, H., and Abou-Donia, M. 2004. Depleted and natural uranium: Chemistry and toxicological effects. J. Toxicol. Environ. Health B 7:297-317.
25. Dickinson, D. A., and Forman, H. J. 2002. Cellular glutathione and thiols metabolism. Biochem. Pharmacol. 64:1019-1026.
26. Dobson, A. W., Lack, A. K., Erikson, K. M., and Aschner, M. 2006. Depleted uranium is not toxic to rat brain endothelial (RBE4) cells. Biol. Trace Elem. Res. 110:61-72.
27. Domingo, J. L. 1994. Metal-induced developmental toxicity in mammals: A review. J. Toxicol. Environ. Health 42:123-141.
28. Domingo, J. L., Llobet, J. M., Tomas, J. M., and Corbella, J. 1987. Acute toxicity of uranium in rats and mice. Bull. Environ. Contam. Toxicol. 39:168-174. (Pubitemid 17120406)
29. Dringen, R. 2000. Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62:649-671.
30. Dublineau, I., Grison, S., Grandcolas, L., Baudelin, C., Tessier, C., Suhard, D., Frelon, S., Cossonnet, C., Claraz, M., Ritt, J., Paquet, P., Voisin, P., and Gourmelon, P. 2006. Absorption, accumulation and biological effects of depleted uranium in Peyer's patches of rats. Toxicology 227:227-339.
31. Dublineau, I., Grison, S., Grandcolas, L., Baudelin, C., Paquet, C. F., Voisin, P., Aigueperse, J., and Gourmelon, P. 2007. Effects of chronic 137Cs ingestion on barrier properties of jejunal epithelium in rats. J. Toxicol. Environ. Health A 70:810-819.
32. Duncan, K. E., Ngu, T. T., Chan, J., Salgado, M. T., Merrifield, M. E., and Stillman, M. J. 2006. Peptide folding, metal-binding mechanisms, and binding site structures in metallothioneins. Exp. Biol. Med. (Maywood) 231:1488-1499.
33. Evans, J., and Hastings, L. 1992. Accumulation of Cd(II) in the CNS depending on the route of administration: intraperitoneal, intratracheal, or intranasal. Fundam. Appl. Toxicol. 19:275-278.
34. Fitsanakis, V. A., Erikson, K. M., Garcia, S. J., Evje, L., Syversen, T., and Aschner, M. 2006. Brain accumulation of depleted uranium in rats following 3- or 6-month treatment with implanted depleted uranium pellets. Biol. Trace Elem. Res. 111:185-197.
35. Freedman, J. H., Slice, L. W., Dixon, D., Fire, A., and Rubin, C. S. 1993. The novel metallothionein genes of Caenorhabditis elegans. Structural organization and inducible, cell-specific expression. J. Biol. Chem. 268:2554-2564.
36. Gally, C., and Bessereau, J. L. 2003. [C. elegans: Of neurons and genes]. Med. Sci. (Paris) 19:725-734.
37. Gehrig, P. M., You, C., Dallinger, R., Gruber, C., Brouwer, M., Kagi, J. H., and Hunziker, P. E. 2000. Electrospray ionization mass spectrometry of zinc, cadmium, and copper metallothioneins: Evidence for metal-binding cooperativity. Protein Sci. 9:395-402.
38. Gilman, A. P., Villeneuve, D. C., Secours, V. E., Yagminas, A. P., Tracy, B. L., Quinn, J. M., Valli, V. E., and Moss, M. A. 1998a. Uranyl nitrate: 91-Day toxicity studies in the New Zealand white rabbit. Toxicol. Sci. 41:129-137.
39. Gilman, A. P., Villeneuve, D. C., Secours, V. E., Yagminas, A. P., Tracy, B. L., Quinn, J. M., Valli, V. E., Willes, R. J., and Moss, M. A. 1998b. Uranyl nitrate: 28-Day and 91-day toxicity studies in the Sprague-Dawley rat. Toxicol. Sci. 41:117-128.
40. Goldman, M., Yaari, A., Doshnitzki, Z., Cohen-Luria, R., and Moran, A. 2006. Nephrotoxicity of uranyl acetate: Effect on rat kidney brush border membrane vesicles. Arch. Toxicol. 80:387-393.
41. Goldstein, G. W. 1984. Brain capillaries: A target for inorganic lead poisoning. Neurotoxicology 5:167-175.
42. Gwiazda, R. H., Squibb, K., McDiarmid, M., and Smith, D. 2004. Detection of depleted uranium in urine of veterans from the 1991 Gulf War. Health Phys. 86:12-18. (Pubitemid 37553588)
43. Hahn, F. F., Guilmette, R. A., and Hoover, M. D. 2002. Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats. Environ. Health Perspect. 110:51-59.
44. Haley, D. P., Bulger, R. E., and Dobyan, D. C. 1982. The long-term effects of uranyl nitrate on the structure and function of the rat kidney. Virchows Arch. B Cell. Pathol. Incl. Mol. Pathol. 41:181-192.
45. Haq, F., Mahoney, M., and Koropatnick, J. 2003. Signaling events for metallothionein induction. Mutat. Res. 533:211-226.
46. Hastings, L., and Evans, J. E. 1991. Olfactory primary neurons as a route of entry for toxic agents into the CNS. Neurotoxicology 12:707-714.
47. Hirata, K., Tsuji, N., and Miyamoto, K. 2005. Biosynthetic regulation of phytochelatins, heavy metal-binding peptides. J. Biosci. Bioeng. 100:593-599.
48. Hodge, S. J., Ejnik, J., Squibb, K. S., McDiarmid, M. A., Morris, E. R., Landauer, M. R., and McClain, D. E. 2001. Detection of depleted uranium in biological samples from Gulf War veterans. Mil. Med. 166(12 suppl.):69-70.
49. Houpert, P., Lestaevel, P., Amourette, C., Dhieux, B., Bussy, C., and Paquet, F. 2004. Effect of U and 137Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat. Can. J. Physiol. Pharmacol. 82:161-166.
50. Houpert, P., Lestaevel, P., Bussy, C., Paquet, F., and Gourmelon, P. 2005. Enriched but not depleted uranium affects central nervous system in long-term exposed rat. Neurotoxicology 26:1015-1020.
51. Hughes, S. L., Bundy, J. G., Want, E. J., Kille, P., and Stürzenbaum, S. R. 2009. The metabolomic responses of Caenorhabditis elegans to cadmium are largely independent of metallothionein status, but dominated by changes in cystathionine and phytochelatins. J. Proteome Res. 8:3512-3519.
52. Ibrulj, S., Krunic-Haveric, A., Haveric, S., Pojskic, N., and Hadziselimovic, R. 2004. Micronuclei occurrence in population exposed to depleted uranium and control human group in correlation with sex, age and smoking habit. Med. Arh. 58:335-338.
53. Ikebuchi, H., Teshima, R., Suzuki, K., Sawada, J., Terao, T., and Yamane, Y. 1986a. An immunological study of a Pb-thionein like protein in rat liver. Biochem. Biophys. Res. Commun. 136:535-541.
54. Ikebuchi, H., Teshima, R., Suzuki, K., Terao, T., and Yamane, Y. 1986b. Simultaneous induction of Pb-metallothionein-like protein and Zn-thionein in the liver of rats given lead acetate. Biochem. J. 233:541-546.
55. Iszard, M. B., Liu, J., and Klaassen, C. D. 1995. Effect of several metallothionein inducers on oxidative stress defense mechanisms in rats. Toxicology 104:25-33.
56. Jakubowski, J., and Kornfeld, K. 1999. A local, high-density, single-nucleotide polymorphism map used to clone Caenorhabditis elegans cdf-1. Genetics 153:743-752.
57. Jiang, G. C.-T., Hughes, S., Stürzenbaum, S. R., Evje, L., Syversen, T., and Aschner, M. 2009. Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium. Toxicol. Sci., 111: 345-354.
58. Jiang, G. C., and Aschner, M. 2006. Neurotoxicity of depleted uranium: Reasons for increased concern. Biol. Trace Elem. Res. 110:1-17.
59. Jones, D. P., Brown, L. A., and Sternberg, P. 1995. Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures. Toxicology 105:267-274.
60. Kalinich, J. F., and McClain, D. E. 2001. Staining of intracellular deposits of uranium in cultured murine macrophages. Biotechnol. Histochem. 76:247-252.
61. Kalinich, J. F., Ramakrishnan, N., Villa, V., and McClain, D. E. 2002. Depleted uranium-uranyl chloride induces apoptosis in mouse J774 macrophages. Toxicology 179:105-114.
62. Knobel, Y., Glei, M., Weise, A., Osswald, K., Schaferhenrich, A., Richter, K. K., Claussen, U., and Pool-Zobel, B. L. 2006. Uranyl nitrilotriacetate, a stabilized salt of uranium, is genotoxic in nontransformed human colon cells and in the human colon adenoma cell line LT97. Toxicol. Sci. 93:286-297.
63. Knudson, A. G. 1996. Hereditary cancer: Two hits revisited. J. Cancer Res. Clin. Oncol. 122:135-140.
64. Kroncke, K. D., Fehsel, K., Schmidt, T., Zenke, F. T., Dasting, I., Wesener, J. R., Bettermann, H., Breunig, K. D., and Kolb-Bachofen, V. 1994. Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9. Biochem. Biophys. Res. Commun. 200:1105-1110
65. Leggett, R. W., and Pellmar, T. C. 2003. The biokinetics of uranium migrating from embedded DU fragments. J. Environ. Radioact. 64:205-225.
66. Lehtinen, M. K., and Bonni, A. 2006. Modeling oxidative stress in the central nervous system. Curr. Mol. Med. 6:871-881.
67. Leiers, B., Kampkotter, A., Grevelding, C. G., Link, C. D., Johnson, T. E., and Henkle-Duhrsen, K. 2003. A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radical Biol. Med. 34:1405-1415.
68. Lemercier, V., Millot, X., Ansoborlo, E., Menetrier, F., Flury-Herard, A., Rousselle,, C., and Scherrmann, J. M. 2003. Study of uranium transfer across the blood-brain barrier. Radiat. Prot. Dosim. 105:243-245.
69. Lestaevel, P., Houpert, P., Bussy, C., Dhieux, B., Gourmelon, P., and Paquet, F. 2005. The brain is a target organ after acute exposure to depleted uranium. Toxicology 212:219-226.
70. Leung, M. C. K., Williams, P. L., Benedetto, A., Au, C., Helmcke, K. J., Aschner, M., and Meyer, J. N. 2008. Caenorhabditis elegans: An emerging model in biomedical and environmental toxicology. Toxicol. Sci. 106:5-28.
71. Li, X., Hao, S., Liu, Y., and Ru, B. 2001. [Study on the form and stability of alpha and beta domain of metallothionein binding to lead (II)]. Wei Sheng Yan Jiu 30:198-200.
72. Lin, W. H., Higgins, D., Pacheco, M., Aletta J.,, Perini, S., Marcucci, K. A., and Roth, J. A. 1993. Manganese induces spreading and process outgrowth in rat pheochromocytoma (PC12) cells. J. Neurosci. Res. 34:546-561.
73. Lindahl, L. S., Bird, L., Legare, M. E., Mikeska, G., Bratton, G. R., and Tiffany-Castiglioni, E. 1999. Differential ability of astroglia and neuronal cells to accumulate lead: Dependence on cell type and on degree of differentiation. Toxicol. Sci. 50:236-243.
74. Malard, V., Prat, O., Darrouzet, E., Berenguer, F., Sage, N., and Quemeneur, E. 2005. Proteomic analysis of the response of human lung cells to uranium. Proteomics 5:4568-4580.
75. Marcotte, E. M., Xenarios, I., van Der Bliek, A. M., and Eisenberg, D. 2000. Localizing proteins in the cell from their phylogenetic profiles. Proc. Natl. Acad. Sci. USA 97:12115-12120.
76. Martin, F., Earl, R., and Tawn, E. J. 1991. A cytogenetic study of men occupationally exposed to uranium. Br. J. Ind. Med. 48:98-102.
77. McDiarmid, M. A., Engelhardt, S. M., and Oliver, M. 2001a. Urinary uranium concentrations in an enlarged Gulf War veteran cohort. Health Phys. 80:270-273.
78. McDiarmid, M. A., Engelhardt, S., Oliver, M., Gucer, P., Wilson, P. D., Kane, R., Kabat, M., Kaup, B., Anderson, L., Hoover, D., Brown, L., Handwerger, B., Albertini, R. J., Jacobson-Kram, D., Thorne, C. D., and Squibb, K. S. 2004. Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up. J. Toxicol. Environ. Health A 67:277-296.
79. McDiarmid, M. A., Keogh, J. P., Hooper, F. J., 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., and Walsh, M. 2000. Health effects of depleted uranium on exposed Gulf War veterans. Environ. Res. 82:168-180.
80. McDiarmid, M. A., Squibb, K., Engelhardt, S., Oliver, M., Gucer, P., Wilson, P. D., Kane, R., Kabat, M., Kaup, B., Anderson, L., Hoover, D., Brown, L., and Jacobson-Kram, D. 2001b. Surveillance of depleted uranium exposed Gulf War veterans: Health effects observed in an enlarged "friendly fire" cohort. J. Occup. Environ. Med. 43:991-1000.
81. McDonald-Taylor, C. K., Singh, A., and Gilman, A. 1997. Uranyl nitrate-induced proximal tubule alterations in rabbits: A quantitative analysis. Toxicol. Pathol. 25:381-389.
82. McDiarmid, M. A., Engelhardt, S. M., Dorsey, C. D., Oliver, M., Gucer, P., Wilson, P. D., Kane, R., Cernich, A., Kaup, B., Anderson, L., Hoover, D., Brown, L., Albertini, R., Gudi, R., and Squibb, K. S. 2009. Surveillance results of depleted uranium-exposed Gulf War I veterans: Sixteen years of follow-up. J. Toxicol. Environ. Health A 72:14-29.
83. Messerle, B. A., Schaffer, A., Vasak, M., Kagi, J. H., and Wuthrich, K. 1990. Three-dimensional structure of human [113Cd7]metallothionein-2 in solution determined by nuclear magnetic resonance spectroscopy. J. Mol. Biol. 214:765-779.
84. Miller, A. C., Blakely, W. F., Livengood, D., Whittaker, T., Xu, J., Ejnik, J. W., Hamilton, M. M., Parlette, E., John, T. S., Gerstenberg, H. M., and Hsu, H. 1998a. Transformation of human osteoblast cells to the tumorigenic phenotype by depleted uranium-uranyl chloride. Environ. Health Perspect. 106:465-471.
85. Miller, A. C., Fuciarelli, A. F., Jackson, W. E., Ejnik, E. J., Emond, C., Strocko, S., Hogan, J., Page, N., and Pellmar, T. 1998b. Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets. Mutagenesis 13:643-648.
86. Mirto, H., Barrouillet, M. P., Henge-Napoli, M. H., Ansoborlo, E., Fournier, M., and Cambar, J. 1999. Influence of uranium(VI) speciation for the evaluation of in vitro uranium cytotoxicity on LLC-PK1 cells. Hum. Exp. Toxicol. 18:180-187.
87. Misra, R. R., Hochadel, J. F., Smith, G. T., Cook, J. C., Waalkes, M. P., and Wink, D. A. 1996. Evidence that nitric oxide enhances cadmium toxicity by displacing the metal from metallothionein. Chem. Res. Toxicol. 9:326-332.
88. Moilanen, L. H., Fukushige, T., and Freedman, J. H. 1999. Regulation of metallothionein gene transcription. Identification of upstream regulatory elements and transcription factors responsible for cell-specific expression of the metallothionein genes from Caenorhabditis elegans. J. Biol. Chem. 274:29655-29665.
89. Monleau, M., De Meo, M., Paquet, F., Chazel, V., Dumenil, G., and Donnadieu-Claraz, M. 2006. Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats. Toxicol. Sci. 89:287-295.
90. Nettesheim, D. G., Engeseth, H. R., and Otvos, J. D. 1985. Products of metal exchange reactions of metallothionein. Biochemistry 24:6744-6751.
91. Otvos, J. D., and Armitage, I. M. 1980. Structure of the metal clusters in rabbit liver metallothionein. Proc. Natl. Acad. Sci. USA 77:7094-7098.
92. Otvos, J. D., Engeseth, H. R., Nettesheim, D. G., and Hilt, C. R. 1987. Interprotein metal exchange reactions of metallothionein. Experientia Suppl. 52:171-178.
93. Ough, E. A., Lewis, B. J., Andrews, W. S., Bennett, L. G., Hancock, R. G., and Scott, K. 2002. An examination of uranium levels in Canadian forces personnel who served in the Gulf War and Kosovo. Health Phys. 82:527-532.
94. Paquet, F., Houpert, P., Blanchardon, E., Delissen, O., Maubert, C., Dhieux, B., Moreels, A. M., Frelon, S., and Gourmelon, P. 2006. Accumulation and distribution of uranium in rats after chronic exposure by ingestion. Health Phys. 90:139-147.
95. Pellmar, T. C., Fuciarelli, A. F., Ejnik, J. W., Hamilton, M., Hogan, J., Strocko, S., Emond, C., Mottaz, H. M., and Landauer, M. R. 1999a. Distribution of uranium in rats implanted with depleted uranium pellets. Toxicol. Sci. 49:29-39.
96. Pellmar, T. C., Keyser, D. O., Emery, C., and Hogan, J. B. 1999b. Electrophysiological changes in hippocampal slices isolated from rats embedded with depleted uranium fragments. Neurotoxicology 20:785-792.
97. Penkowa, M. 2006. Metallothioneins are multipurpose neuroprotectants during brain pathology. FEBS J. 273:1857-1870.
98. Penkowa, M., Nielsen, H., Hidalgo, J., Bernth, N., and Moos, T. 1999. Distribution of metallothionein I+II and vesicular zinc in the developing central nervous system: Correlative study in the rat. J. Comp. Neurol. 412:303-318.
99. Periyakaruppan, A., Kumar, F., Sarkar, S., Sharma, C. S., and Ramesh, G. T. 2007. Uranium induces oxidative stress in lung epithelial cells. Arch. Toxicol. 81:389-395.
100. Prat, O., Berenguer, F., Malard, V., Tavan, E., Sage, N., Steinmetz, G., and Quemeneur, E. 2005. Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity. Proteomics 5:297-306.
101. Richter-Landsberg, C., and Goldbaum, O. 2003. Stress proteins in neural cells: Functional roles in health and disease. Cell Mol. Life Sci. 60:337-349.
102. Robbins, A. H., McRee, D. E., Williamson, M., Collett, S. A., Xuong, N. H., Furey, W. F., Wang, B. C., and Stout, C. D. 1991. Refined crystal structure of Cd, Zn metallothionein at 2.0 A resolution. J. Mol. Biol. 221:1269-1293.
103. Robbins, A. H., and Stout, C. D. 1991. X-ray structure of metallothionein. Methods Enzymol. 205:485-502.
104. Roh, J. Y., Lee, J., and Choi, J. 2006. Assessment of stress-related gene expression in the heavy metal-exposed nematode Caenorhabditis elegans: A potential biomarker for metal-induced toxicity monitoring and environmental risk assessment. Environ. Toxicol. Chem. 25:2946-2956.
105. Schwarz, M. A., Lazo, J. S., Yalowich, J. C., Allen, W. P., Whitmore, M., Bergonia, H. A., Tzeng, E., Billiar, T. R., Robbins, P. D., Lancaster, J. R., Jr., and Pitt, B. R. 1995. Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide. Proc. Natl. Acad. Sci. USA 92:4452-4456.
106. Scott, K. 2003. Lung burdens of depleted uranium in Gulf War veterans. Mil. Med. 168:ii; author reply ii.
107. Slice, L. W., Freedman, J. H., and Rubin, C. S. 1990. Purification, characterization, and cDNA cloning of a novel metallothionein-like, cadmium-binding protein from Caenorhabditis elegans. J. Biol. Chem. 265:256-263.
108. Squibb, K. S., and McDiarmid, M. A. 2006. Depleted uranium exposure and health effects in Gulf War veterans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361:639-648.
109. Stearns, D. M., Yazzie, M., Bradley, A. S., Coryell, V. H., Shelley, J. T., Ashby, A., Asplund, C. S., and Lantz, R. C. 2005. Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells. Mutagenesis 20:417-423.
110. Tatusova, T. A., and Madden, T. L. 1999. BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol. Lett. 174:247-250.
111. Taulan, M., Paquet, F., Maubert, C., Delissen, O., Demaille, J., and Romey, M. C. 2004. Renal toxicogenomic response to chronic uranyl nitrate insult in mice. Environ. Health Perspect. 112:1628-1635.
112. Taylor, D. M., and Taylor, S. K. 1997. Environmental uranium and human health. Rev. Environ. Health 12:147-157.
113. Thun, M. J., Baker, D. B., Steenland, K., Smith, A. B., Halperin, W., and Berl, T. 1985. Renal toxicity in uranium mill workers. Scand. J. Work Environ. Health 11:83-90.
114. Tiffany-Castiglioni, E., and Qian, Y. 2001. Astroglia as metal depots: Molecular mechanisms for metal accumulation, storage and release. Neurotoxicology 22:577-592.
115. Tirmarche, M., Baysson, H., and Telle-Lamberton, M. 2004. [Uranium exposure and cancer risk: A review of epidemiological studies]. Rev. Epidemiol. Sante Publique 52:81-90. (Pubitemid 38468655)
116. Tomlinson, I. P., Roylance, R., and Houlston, R. S. 2001. Two hits revisited again. J. Med. Genet. 38:81-85.
117. Vatamaniuk, O. K., Bucher, E. A., Sundaram, M. V., and Rea, P. A. 2005. CeHMT-1, a putative phytochelatin transporter, is required for cadmium tolerance in Caenorhabditis elegans. J. Biol. Chem. 280:23684-23690.
118. Wadsworth, W. G., and Hedgecock, E. M. 1992. Guidance of neuroblast migrations and axonal projections in Caenorhabditis elegans. Curr. Opin. Neurobiol. 2:36-41.
119. Wilhelmsen, T. W., Olsvik, P. A., Hansen, B. H., and Andersen, R. A. 2002. Evidence for oligomerization of metallothioneins in their functional state. J. Chromatogr. A 979:249-254.
120. Yang, Z. H., Fan, B. X., Lu, Y., Cao, Z. S., Yu, S., Fan, F. Y., and Zhu, M. X. 2002. [Malignant transformation of human bronchial epithelial cell (BEAS-2B) induced by depleted uranium]. Ai Zheng 21:944-948.
121. Yazzie, M., Gamble, S. L., Civitello, E. R., and Stearns, D. M. 2003. Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (vitamin C). Chem. Res. Toxicol. 16:524-530.
122. You, C., Mackay, E. A., Gehrig, P. M., Hunziker P. E.,, and Kagi, J. H. 1999. Purification and characterization of recombinant Caenorhabditis elegans metallothionein. Arch. Biochem. Biophys. 372:44-52.
123. Young, J. K. 1994. Glial metallothionein. Biol. Signals 3:169-175.
124. Young, J. K., Garvey, J. S., and Huang, P. C. 1991. Glial immunoreactivity for metallothionein in the rat brain. Glia 4:602-610.
125. Zangger, K., and Armitage, I. M. 2002. Dynamics of interdomain and intermolecular interactions in mammalian metallothioneins. J. Inorg. Biochem. 88:135-143.
126. Zangger, K., Oz, G., Haslinger, E., Kunert, O., and Armitage, I. M. 2001. Nitric oxide selectively releases metals from the amino-terminal domain of metallothioneins: Potential role at inflammatory sites. FASEB J. 15:1303-1305.
127. Zangger, K., Oz, G., Otvos, J. D., and Armitage, I. M. 1999. Three-dimensional solution structure of mouse [Cd7]-metallothionein-1 by homonuclear and heteronuclear NMR spectroscopy. Protein Sci. 8:2630-2638.
128. Zhu, L. R., Thomas, P. E., Lu, G., Reuhl, K. R., Yang, G. Y., Wang, L. D., Wang, S. L., Yang, C. S., He, X. Y., and Hong, J. Y. 2006. CYP2A13 in human respiratory tissues and lung cancers: An immunohistochemical study with a new peptide-specific antibody. Drug Metab. Dispos. 34:1672-1676.