| Implanted Depleted Uranium Fragments Cause Soft Tissue Sarcomas in the Muscles of Rats Fletcher F. Hahn, Raymond A. Guilmette, and Mark D. Hoover Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA Abstract
In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta) , as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide (232Th) , Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5  2.5 1.5 mm or 5.0 5.0 1.5 mm) or four pellets (2.0 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 5.0 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 2.5 mm DU squares and with 5.0 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats. Key words: bioassay, carcinogenesis, depleted uranium, Gulf War, rats, sarcomas, soft tissues, tantalum, Thorotrast. Environ Health Perspect 110:51-59 (2002) . [Online 15 December 2001] http://ehpnet1.niehs.nih.gov/docs/2002/110p51-59hahn/ abstract.html Address correspondence to F.F. Hahn, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 USA. Telephone: (505) 348-9428. Fax: (505) 348-4980. E-mail: fhahn@lrri.org We thank G. Brand, Durham, NH, for his helpful suggestions in experimental design of the study, D. Lundgren for his organizational help in initiating the study, and J. Kubatko for his help with the statistical analyses. Research was sponsored by the U.S. Army Medical Research and Materiel Command, MIPR No. KVFM5529 with the U.S. DOE, under Cooperative Agreement DE-FC04-96AL76406. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. Received 2 November 2000 ; accepted 28 June 2001.
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