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 microg/cm2 UO3 induced 99, 57, 32, and 1% relative survival, respectively. Similarly, 100, 200, 400, and 800 microM 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 microg/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.