Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to stud...

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Veröffentlicht in:Environmental Health Perspectives. - National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare, 1972. - 106(1998), 8, Seite 465-471
1. Verfasser: Miller, Alexandra C. (VerfasserIn)
Weitere Verfasser: Blakely, William F., Livengood, David, Whittaker, Tim, Xu, Jiaquan, Ejnik, John W., Hamilton, Matthew M., Parlette, Eric, St. John, Theodore, Gerstenberg, Henry M., Hsu, Hannah
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 1998
Zugriff auf das übergeordnete Werk:Environmental Health Perspectives
Schlagworte:Alpha radiation Depleted uranium Osteoblast Transformation Physical sciences Biological sciences Health sciences
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245 1 0 |a Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride 
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520 |a Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracellular and extracellular uranium levels, showed that few (0.0014%) cell nuclei were hit by alpha particles. We report the ability of DU-uranyl chloride to transform immortalized human osteoblastic cells (HOS) to the tumorigenic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumor-suppressor protein, and elevated levels of sister chromatid exchanges per cell. DU-uranyl chloride treatment resulted in a 9.6 (± 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted in a 7.1 (± 2.1)-fold increase in transformation frequency. This is the first report showing that a DU compound caused human cell transformation to the neoplastic phenotype. Although additional studies are needed to determine if protracted DU exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel). 
650 4 |a Alpha radiation 
650 4 |a Depleted uranium 
650 4 |a Osteoblast 
650 4 |a Transformation 
650 4 |a Physical sciences  |x Chemistry  |x Chemical elements  |x Metals  |x Uranium 
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650 4 |a Health sciences  |x Medical conditions  |x Diseases  |x Neoplasia  |x Tumors 
650 4 |a Physical sciences  |x Chemistry  |x Chemical compounds  |x Functional groups  |x Acetates  |x Lead acetates 
650 4 |a Physical sciences  |x Physics  |x Microphysics  |x Particle physics  |x Subatomic particles  |x Bosons  |x Alpha particles 
650 4 |a Health sciences  |x Health and wellness  |x Public health  |x Health hazards  |x Chemical hazards 
650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Cultured cells  |x Cell lines 
650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Cultured cells  |x Cell lines  |x Tumor cell line 
650 4 |a Biological sciences  |x Biology  |x Genetics  |x Phenotypes 
650 4 |a Physical sciences  |x Chemistry  |x Chemical compounds  |x Halogen compounds  |x Chlorine compounds  |x Chlorides  |x Research 
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700 1 |a Blakely, William F.  |e verfasserin  |4 aut 
700 1 |a Livengood, David  |e verfasserin  |4 aut 
700 1 |a Whittaker, Tim  |e verfasserin  |4 aut 
700 1 |a Xu, Jiaquan  |e verfasserin  |4 aut 
700 1 |a Ejnik, John W.  |e verfasserin  |4 aut 
700 1 |a Hamilton, Matthew M.  |e verfasserin  |4 aut 
700 1 |a Parlette, Eric  |e verfasserin  |4 aut 
700 1 |a St. John, Theodore  |e verfasserin  |4 aut 
700 1 |a Gerstenberg, Henry M.  |e verfasserin  |4 aut 
700 1 |a Hsu, Hannah  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Environmental Health Perspectives  |d National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare, 1972  |g 106(1998), 8, Seite 465-471  |w (DE-627)34134639X  |w (DE-600)2067353-X  |x 00916765  |7 nnns 
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856 4 0 |u https://doi.org/10.2307/3434178  |3 Volltext 
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