| Autor: |
Xu, Jiaquan, St. John, Theodore, Parlette, Eric, Livengood, David, Hsu, Hannah, Gerstenberg, Henry M., Hamilton, Matthew M., Whittaker, Tim, Miller, Alexandra C., Blakely, William F., Ejnik, John W. |
| Předmět: |
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| Zdroj: |
Environmental Health Perspectives. Aug1998, Vol. 106 Issue 8, p465. 0p. |
| Abstrakt: |
Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uraniumexposure 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 ofDU-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 (1 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted ina 7.1 (1 2.1)-fold increase in transformation frequency. This is thefirst 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 cancerinduction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel). [ABSTRACT FROM AUTHOR] |
| Databáze: |
GreenFILE |
| Externí odkaz: |
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