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Depleted uranium – uranyl chloride induces apoptosis in mouse J774-macrophages (2002)

AuteurKalinich, Ramakrishnan
6-05-0-00-30.pdf
Datumjuni 2002
Classificatie 6.05.0.00/30 (VERARMD URANIUM - ALGEMEEN (oa. Gezondheidsonderzoek))
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Uit de publicatie:

                                                  Toxicology 179 (2002) 105 Á/114
                                                                                               www.elsevier.com/locate/toxicol




Depleted uraniumÁ uranyl chloride induces apoptosis in mouse
                                        /



                    J774 macrophages
John F. Kalinich *, Narayani Ramakrishnan 1, Vilmar Villa, David E. McClain
 Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD
                                                      20889-5603, USA

                   Received 27 February 2002; received in revised form 17 May 2002; accepted 9 June 2002




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 Á/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 mM depleted uranium Á/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 mM depleted uranium Á/uranyl chloride were apparent within 2 h. Other
events associated with apoptosis, including morphological changes and DNA fragmentation, were also apparent after
depleted uranium Á/uranyl chloride treatment. These results suggest that the uptake and concentration of s