Observation of Radiation-specific Damage in Human Cells Exposed to Depleted Uranium: Dicentric Frequency and Neoplastic Transformation as Endpoints

Abstract

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalised human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha-particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown and the involvement of radiation in DU-induced biological effects could have significant implications for current risk estimates for internalised DU exposure. Two approaches were used to address this question. The frequency of dicentrics was measured in HOS cells following DU exposure in vitro. Data demonstrated that DU exposure (50 microM, 24 h) induced a significant elevation in dicentric frequency in vitro in contrast to incubation with the heavy metals, nickel and tungsten which did not increase dicentric frequency above background levels. Using the same concentration (50 microM) of three uranyl nitrate compounds that have different uranium isotopic concentrations and therefore, different specific activities, the effect on neoplastic transformation in vitro was examined. HOS cells were exposed to one of three-uranyl nitrate compounds (238U-uranyl nitrate, specific activity 0.33 microCi.g-1; DU-uranyl nitrate, specific activity 0.44 microCi.g-1; and 235U-uranyl nitrate, specific activity 2.2 microCi.g-1) delivered at a concentration of 50 microM for 24 h. Results showed, at equal uranium concentration, there was a specific activity dependent increase in neoplastic transformation frequency. Taken together these data suggest that radiation can play a role in DU-induced biological effects in vitro.

Depleted uranium-catalyzed oxidative DNA damage: absence of significant alpha particle decay

“…While these findings might suggest these heavy metals are unknown. Our laboratory has used that the chemical component of DU could be primarily both an in vitro human cell-model and rodent studies to responsible for the transforming effects, recent cellular examine the potential late health effects of these heavy transformation and cytogenetic findings from our laboratory have shown that alpha particles are involved in the neoplastic transformation process [13]. Furthermore, the *Corresponding author.…”

“…Bystander effects, whereby cells that are not directly Genomic instability ↑ Genotoxicity / genomic instability [11][12][13] exposed to radiation exhibit adverse biological effects, however assumes that the second-order rate constant for have been observed in a number of experimental systems.…”

“…Therefore, the ? particle radiation is involved in DU-induced effects [13], chemically generated OH might exceed radioactively ? 7 although chemical effects cannot be ruled out.…”

Gulf war depleted uranium risks

“…Miller et al (1998), using in vitro tests with DU chloride, found that human osteoblast cells can be transformed into the tumorigenic phenotype. The authors of the study point out that the dose-effect relationship is similar to that observed for nonradioactive heavy metals; however, a later study (Miller et al, 2002) showed an approximately linear relationship between transformation frequency and specific activity (nuclear disintegrations/s Á g) for the same uranium concentrations. Also, Miller observed a significant increase in dicentric frequency for in vitro tests with DU that was not observed for nonradioactive heavy metals.…”

“…Reports in the popular press of serious health effects from DU exposure often include misinterpretations of scientific reports, unsubstantiated claims, and false claims. Some excellent scientific studies have investigated DU health effects at the cellular level (e.g., Miller et al, 2002) or by testing animals exposed to DU (e.g., Domingo et al, 1989). These studies suggest possible chemically induced cancer risks, birth defects, immune system impairment, etc.…”