Abstract Title:

Depleted uranium-uranyl chloride induces apoptosis in mouse J774 macrophages.

Abstract Source:

Toxicology. 2002 Sep 30;179(1-2):105-14. PMID: 12204547

Abstract Author(s):

John F Kalinich, Narayani Ramakrishnan, Vilmar Villa, David E McClain

Article Affiliation:

Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA. [email protected]

Abstract:

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 microM 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 microM 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.

Study Type : In Vitro Study
Additional Links
Problem Substances : Uranium : CK(125) : AC(36)
Adverse Pharmacological Actions : Immunotoxic : CK(484) : AC(118)

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