Particulate Depleted Uranium Is Cytotoxic and Clastogenic to Human Lung Cells

Abstract

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cells. Accordingly, we determined the cytotoxicity and clastogenicity of both particulate (water-insoluble) and soluble DU in human bronchial fibroblasts (WTHBF-6 cells). We used uranium trioxide (UO3) and uranyl acetate (UA) as prototypical particulate and soluble DU salts, respectively. After a 24 h exposure, both UO3 and UA induced concentration-dependent cytotoxicity in WTHBF-6 cells. Specifically, 0.1, 0.5, 1, and 5 μg/cm2 UO3 induced 99, 57, 32, and 1% relative survival, respectively. Similarly, 100, 200, 400, and 800 μM UA induced 98, 92, 70, and 56% relative survival, respectively. When treated with chronic exposure, up to 72 h, of either UO3 or UA, there was an increased degree of cytotoxicity. We assessed the clastogenicity of these compounds and found that at concentrations of 0, 0.5, 1, and 5 μg/cm2 UO3, 5, 6, 10, and 15% of metaphase cells exhibit some form of chromosome damage. UA did not induce chromosome damage above background levels. There were slight increases in chromosome damage induced when we extended the UO3 treatment time to 48 or 72 h, but no meaningful increase in chromosome damage was observed with chronic exposure to UA.

Stress Shaping Brains: Higher Order DNA/Chromosome Mechanisms Underlying Epigenetic Programming of the Brain Transcriptome

“…Particulate depleted uranium (DU), widely suspected as one of the prime causes of PGWS associated pathologies, compounds were demonstrated to induce time and concentration-dependent cytotoxic (producing a toxic effect on cells) and clastogenic (causing disruption or breakages of chromosomes) effects in human lung cells. The types of aberrations seen with treatment of particulate DU are consistent with those induced by other carcinogenic metals (Wise et al, 2007). Tests of 5 Gulf War Veterans in 2007 analysed by Wayne State University Medical staff revealed the 5 Veterans studied have severe chromosome damage.…”

The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

“…An analysis of Gulf War I veterans exposed to alpha particle emitting depleted uranium has also identified a significant 50% increase in HPRT mutant frequency compared to a low exposure group [106] and a number of other studies have also observed the mutagenic and clastogenic potential of depleted uranium exposure [107,108]. …”

Toxicity of depleted uranium complexes is independent of p53 activity

“…[3, 4]. The high density (19.1 g/cm 3 ) and pyrophoric properties of depleted uranium make it desirable as fuel for nuclear reactors and as raw material for making both ammunition and tank armor for the military [5, 6]. …”