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

Abstract

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 enxst rding the long-term health effects of internaized DU in humans. We established an in viuro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracelular and etacelular u m levels, showed that few (0.0014%) cell nuldei were hit by alph partidles. We report the ability of DU-uranyl chloride to tansform immortalized human osteoblastic cells (HOS) to the tumoriWnic 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 tumorsuppressor protein, and elevated levels of sister chromatid nges per cell. DU-uranyl

Seasonal and spatial variability of 210Po, 238U and 239+240Pu levels in the river catchment area assessed by application of neural-network based classification

“…The presence of uranium in the body can cause damage to the kidneys, leading to nephritis (Tutu et al, 2005). In addition, the genotoxic effect has been studied (Miller et al, 1998) and detailed description of the toxicological effects of depleted uranium can be found elsewhere (Patočka et al, 2004).…”

Cytogenetic biomonitoring of inhabitants of a large uranium mineralization area: the municipalities of Monte Alegre, Prainha, and Alenquer, in the State of Pará, Brazil

“…The in vitro exposure of different cell types to DU increased the frequency of MN (Miller et al 2001a(Miller et al , b, 2003 and the phenotype transformation rate of the cells (Miller et al 1998). Yazzie et al (2003) reported that the inhaling of DU by rats can produce breaks and oxidative damage to the nitrogenated bases of the DNA.…”

Biological monitoring and surveillance results of Gulf War I veterans exposed to depleted uranium

“…Studies in Chinese hamster ovary (CHO) cells exposed to uranyl nitrate (UO 2 2+ ) found an increased frequency of micronuclei, SCE and CAs (Lin et al 1993). In a human osteoblast (HOS) cell line, increased SCE and an increase in transformation to a tumorigenic phenotype was seen in DU exposed cells in culture (Miller et al 1998a). Miller et al (1998b) also showed increased urine mutagenicity in TA98 and AMES II (TA 7001-7006) in DU-implanted animals.…”