Depleted uranium–uranyl chloride induces apoptosis in mouse J774 macrophages

• Published in: Toxicology (Amsterdam) 2002-09, Vol.179 (1), p.105-114
• Main Authors: Kalinich, John F, Ramakrishnan, Narayani, Villa, Vilmar, McClain, David E
• Format: Article
• Language: English
• Subjects: Animals; Annexin A5 - metabolism; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biological effects of radiation; Cell Line; Cell Survival - drug effects; Chlorides - toxicity; Colorimetry; Depleted uranium; DNA Fragmentation - drug effects; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Ionizing radiations; Macrophages; Macrophages - drug effects; Mice; Phosphatidylserines - metabolism; Programmed cell death; Tissues, organs and organisms biophysics; Uranium - toxicity
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(02)00318-9

Depleted uranium entering the body as a result of inhalation or embedded fragments becomes associated to a great extent with macrophages. As part of our continuing studies on the health effects of internalized depleted uranium, we investigated the effect of soluble depleted uranium–uranyl chloride on the mouse macrophage cell line, J774. Using a cytochemical staining protocol specific for uranium, we found that uranium uptake by the macrophages increased in a time-dependent manner. Treatment with 1, 10, or 100 μM depleted uranium–uranyl chloride resulted in decreased viability of the J774 cells within 24 h. Flow cytometric analysis of the treated cells with annexin V showed the translocation of phosphatidylserine from the inner face of the plasma membrane to the outer surface indicating the loss of phospholipid symmetry and the beginning of the apoptotic process. Significant differences in annexin V labeling between control cells and cells treated with 100 μM depleted uranium–uranyl chloride were apparent within 2 h. Other events associated with apoptosis, including morphological changes and DNA fragmentation, were also apparent after depleted uranium–uranyl chloride treatment. These results suggest that the uptake and concentration of soluble depleted uranium by macrophages initiates events that results in the apoptotic death of these cells.