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

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 immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha particle) and a 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. In the current study we demonstrate that DU can generate oxidative DNA damage and can also catalyze reactions that induce hydroxyl radicals in the absence of significant alpha particle decay. Experiments were conducted under conditions in which chemical generation of hydroxyl radicals was calculated to exceed the radiolytic 6 generation by 10 -fold. The data showed that markers of oxidative DNA base damage, thymine glycol and 8-deoxyguanosine could be induced from DU-catalyzed reactions of hydrogen peroxide and ascorbate similarly to those occurring in the presence of iron catalysts. DU was 6-fold more efficient than iron at catalyzing the oxidation of ascorbate at pH 7. These data not only demonstrate that DU at pH 7 can induced oxidative DNA damage in the absence of significant alpha particle decay, but also suggest that DU can induce carcinogenic lesions, e.g. oxidative DNA lesions, through interaction with a cellular oxygen species. Published by Elsevier Science Inc. The in vivo effects of internalized DU include enhanceDesert Storm were wounded in friendly fire accidents and ment of urine mutagenicity, oncogene activation, and currently have retained large fragments (|2-20 mm) of uranium redistribution to multiple organs. A review of our depleted uranium (DU) in their bodies. The use of DU in findings is shown in Table 1 [ [3][4][5][6][7][8][9][10][11][12]. military applications worldwide could result in soldiers DU, unlike natural uranium, which is considered to be with imbedded heavy metal shrapnel. Chemically similar both a radiological and a chemical (heavy metal) hazard to natural uranium [1], DU is a low specific activity heavy[1], is not believed to be a significant radiation hazard metal, with a density |1.7-times that of lead (19 vs. 11.35 because of its low specific activity. Studies with DU in our 3 g / cm ). DU differs from natural uranium in that it has laboratory demonstrated neoplastic transformation of 235 234 been depleted of U and U. As a result, the specific human cells under conditions in which |14% of the activity of DU is significantly less than natural uranium DU-exposed cells were transformed but with less than 5% (0.44 vs. 0.7 mCi / g, respectively) [2].of the DU-exposed cells actually being traversed by an The acute and long-term health effects of exposure to alpha particle [4,8,9]. 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 ...

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